Journal articles on the topic 'PHARMA] Life Sciences'

AbstractDeep Learning has boosted artificial intelligence over the past 5 years and is seen now as one of the major technological innovation areas, predicted to replace lots of repetitive, but complex tasks of human labor within the next decade. It is also expected to be ‘game changing’ for research activities in pharma and life sciences, where large sets of similar yet complex data samples are systematically analyzed. Deep learning is currently conquering formerly expert domains especially in areas requiring perception, previously not amenable to standard machine learning. A typical example is the automated analysis of images which are typically produced en-masse in many domains, e. g., in high-content screening or digital pathology. Deep learning enables to create competitive applications in so-far defined core domains of ‘human intelligence’. Applications of artificial intelligence have been enabled in recent years by (i) the massive availability of data samples, collected in pharma driven drug programs (=‘big data’) as well as (ii) deep learning algorithmic advancements and (iii) increase in compute power. Such applications are based on software frameworks with specific strengths and weaknesses. Here, we introduce typical applications and underlying frameworks for deep learning with a set of practical criteria for developing production ready solutions in life science and pharma research. Based on our own experience in successfully developing deep learning applications we provide suggestions and a baseline for selecting the most suited frameworks for a future-proof and cost-effective development.

Abstract Background Ulcerative colitis (UC) can result in a high prevalence of bowel movement urgency (BU), significantly reducing patient quality of life. Purpose Early BU improvement association with later clinical endpoint improvements was examined in moderately-to-severely active UC patients (pts) treated with mirikizumab (miri). Method BU was evaluated in Phase 3 randomized placebo (PBO)-controlled 12-week induction (LUCENT-1, NCT03518086) and 40-week maintenance (LUCENT-2, NCT03524092) trials with miri. Pts received IV miri 300mg or PBO during induction. Week (W)12 miri responders were rerandomized at LUCENT-2 baseline (BL) to subcutaneous miri 200mg or PBO. BU was measured with 11-point Urgency Numeric Rating Scale (UNRS) from 0 (no urgency) to 10 (worst possible). Pts’ UNRS scores were an average from 7 consecutive days prior to visit. Association of pts with BU Clinically Meaningful Improvement (CMI) or BU remission between BL and W4 with the proportion of pts achieving clinical response, and clinical, endoscopic, or symptomatic remission at end of W12 was assessed. For pts who achieved clinical response at W12, the analyses were repeated for the end of maintenance based on W12 BU status. Logistic regression models with treatment, urgency (BU CMI or BU Remission), treatment-by-urgency group interaction, and stratification factors were fitted to examine the association between early urgency improvement and later clinical endpoints. Result(s) Treatment-by-urgency group interactions were not statistically significant across clinical outcomes for induction and maintenance. For induction, treatment and urgency status were statistically significant. Pts experiencing BU CMI or BU remission at W4 were consistently more likely to achieve clinical response, and clinical, endoscopic, or symptomatic remission at W12 for both treatment groups. For remission, only treatment main effect was statistically significant. Among miri induction clinical responders (an enriched population), BU CMI or BU Remission at end of induction (W12) was not associated with later maintenance efficacy outcomes (W52). Miri-treated pts achieved higher rates of clinical response, and clinical, endoscopic, or symptomatic remission at W52 than with PBO regardless of BU CMI or BU Remission at W12 (Table). Image Conclusion(s) Early BU Improvement, CMI or Remission, was associated with better clinical outcomes during induction for miri and PBO pts, showing BU is a sensitive predictor of early clinical outcomes. Among miri induction responders, miri consistently provided better maintenance of response and remission rates than PBO. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Eli Lilly and Company Disclosure of Interest D. Clemow Employee of: Eli Lilly and Company, C. Sapin Employee of: Eli Lilly and Company, T. Hibi Grant / Research support from: AbbVie, ActivAid, Alfresa Pharma, Bristol Myers Squibb, Eli Lilly Japan K.K., Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceutical K.K., JMDC, Mochida Pharmaceutical, Nippon Kayaku, Pfizer Japan, and Takeda, Consultant of: AbbVie, Apo Plus Station, Bristol Myers Squibb, Celltrion, EA Pharma, Eli Lilly and Company, Gilead Sciences, Janssen, Kyorin, Mitsubishi Tanabe Pharma, Nichi-Iko Pharmaceutical, Pfizer, Takeda, and Zeria Pharmaceutical, Speakers bureau of: AbbVie, Aspen Japan K.K., Ferring Pharmaceuticals, Gilead Sciences, Janssen, JIMRO, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, and Takeda, M. Dubinsky Shareholder of: Trellus Health, Grant / Research support from: AbbVie, Janssen, Pfizer, and Prometheus Biosciences, Consultant of: AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, F. Hoffmann-La Roche, Genentech, Gilead Sciences, Janssen, Pfizer, Prometheus Therapeutics and Diagnostics, Takeda, and UCB Pharma, S. Vermeire Consultant of: AbbVie, Arena Pharmaceuticals, Avaxia Biologics, Boehringer Ingelheim, Celgene, Dr. Falk Pharma, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Gilead Sciences, Hospira, Janssen, Mundipharma, Merck Sharp & Dohme, Pfizer, ProDigest, Progenity, Prometheus Therapeutics and Diagnostics, Robarts Clinical Trials, Second Genome, Shire, Takeda, Theravance Biopharma, and Tillots Pharma AG, Speakers bureau of: AbbVie, Dr. Falk Pharma, Ferring Pharmaceuticals, Galapagos NV, Genentech/Roche, Gilead Sciences, Janssen, Pfizer, Robarts Clinical Trials, and Takeda, S. Schreiber Grant / Research support from: personal fees and/or travel support from: AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly and Company, Dr. Falk Pharma, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos NV, Gilead Sciences, I-MAB Biopharma, Janssen, Merck Sharp & Dohme, Mylan, Novartis, Pfizer, Protagonist Therapeutics, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Theravance Biopharma, and UCB Pharma, T. Gibble Employee of: Eli Lilly and Company, L. Peyrin-Biroulet Grant / Research support from: AbbVie, Fresenius Kabi, Merck Sharp & Dohme, and Takeda, Consultant of: AbbVie, Alimentiv, Allergan, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly and Company, Enthera, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos NV, Genentech, Gilead Sciences, Gossamer Bio, InDex Pharmaceuticals, Inotrem, Janssen, Merck Sharp & Dohme, Mylan, Norgine, Ono Pharmaceutical, OSE Immunotherapeutics, Pandion Therapeutics, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Theravance Biopharma, Thermo Fisher Scientific, Tillots Pharma AG, Viatris, and Vifor Pharma, M. Watanabe Grant / Research support from: AbbVie, Alfresa Pharma, EA Pharma, Kissei, Kyorin, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Takeda, and Zeria Pharmaceutical, Consultant of: AbbVie, Boehringer Ingelheim, EA Pharma, Eli Lilly Japan K.K., Gilead Sciences, Nippon, and Takeda, Speakers bureau of: EA Pharma, Eli Lilly Japan K.K., Gilead Sciences, Janssen, JIMRO, Kissei, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer Japan, Takeda, and Zeria Pharmaceutical, R. Panaccione Grant / Research support from: AbbVie, Ferring Pharmaceuticals, Janssen, Pfizer, and Takeda, Consultant of: Abbott, AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmo Pharmaceuticals, Eisai, Elan Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Therapeutics, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, and UCB Pharma, J. Jones: None Declared

Plenaries and Special Presentations:Carolyn Buser-Doepner, GSK: "New Trends in Pharma-Academia Collaborations for Drug Discovery"Chris Halyk, President, Janssen Inc.: "Are Innovative Medicines and our Life Sciences Industry at Risk in Canada?"Aaron Schimmer, Princess Margaret Cancer Centre: "New Therapeutic Strategies to Target the Mitochondria in Leukemia"Ivana Cecic, Genome BC: "Genomics in Canada: From Knowledge Generation to Patient Outcomes"Adam Rosebrock, University of Toronto: "Quantitative Mass-Spectrometry Metabolomics for Direct Biochemical Phenotyping"Fakhreddin Jamali, University of Alberta: CSPS Lifetime Achievement Award Lecture - "Pharmaceutical Research and Development, Lessons Learned"Conference Sessions:Special Session: Innovation and Management of Modern Pharmaceuticals1. Special Populations2. Nanomedicines Become Personal: Opportunities and Challenges3. Mucosal Drug Delivery4. Broaching the Fourth Hurdle: Getting Drugs on the Formulary5. Pharmacogenomics in the Clinic and Community6. Responsive Drug Delivery Systems7. Drug Targeting and Targeting Drugs8. Health Sustainability Evidence9. Integrating Pharmaceutical Sciences into a Pharm D Curriculum10. Analytical Innovation to Support Precision Medicine and Biologicals Development11. Protein and Peptide Delivery

Intellectual Property is a powerful legal and economic instrument. In our “knowledge economy”, patents are the preferred IP tool with special emphasis in the pharma – agro biotech industry. However, the growth of patents in the bio sector such as the pharma and agro fields, encounters many challenges. Life itself has not been defined yet. So, how can it be determined exactly when a living being, or a biological entity has been modified by itself or by human intervention, and thus address issues of patentability? Therefore, a researcher in the bio field cannot be alien to Intellectual Property, being the main actor in the revolution of the bio-pharma-agro sectors.

Abstract Background The inflammatory bowel disease questionnaire (IBDQ) is a measure of health-related quality of life (QoL), with higher scores indicating greater QoL. In a prior phase 2 study (NCT02589665), mirikizumab, an anti-IL23p19 antibody, demonstrated efficacy and improvement in IBDQ scores in participants with moderately to severely active ulcerative colitis (UC). Purpose This analysis evaluated effect of mirikizumab (miri) vs placebo (PBO) on IBDQ scores in patients (pts) with moderately to severely active ulcerative colitis (UC) who had failed prior conventional or biologic therapy in a Phase 3, double-blind, 12-week (W) induction study (LUCENT-1) followed by a 40W maintenance study (LUCENT-2) for a total of 52W continuous therapy. Method Pts (N=1162) in LUCENT-1 were randomized 3:1 to receive 300mg miri or PBO intravenously once every four weeks (Q4W). 544 pts who achieved Modified Mayo Score Clinical Response to miri by W12 of induction were rerandomized 2:1 in LUCENT-2 to subcutaneous miri 200mg or PBO Q4W in maintenance period. Randomization was stratified by previous biologic therapy failure, baseline corticosteroid use, and region. LUCENT-1 stratification included baseline (BL) disease activity, and LUCENT-2 included LUCENT-1 clinical remission status. The least squares mean change from BL in IBDQ scores at W12 of induction and W40 of maintenance was determined using analysis of covariance models. BL was W0 of therapy and stratification factors and BL scores were used as covariates. The Minimal Clinically Important Difference (MCID) was defined as an improvement of ≥16 points in total IBDQ score (IBDQ response) and IBDQ remission as a total score ≥170 points. IBDQ response and remission were calculated using non-responder imputations. Treatments were compared using the common risk difference (risk diff). Result(s) Miri treatment resulted in significantly greater improvement from BL in IBDQ total and domain scores vs PBO at both W12 of induction and W40 of maintenance (52W treatment) (Table). The proportions of pts who achieved an IBDQ response was significantly greater for miri treated pts vs PBO at W12 (risk diff =17.1[95%CI:10.7, 23.5]) and W40 (29.5 [21.0, 37.9]). Significantly greater proportions of pts receiving miri achieved IBDQ remission at W12 (18.1 [11.8, 24.4]) and W40 (28.5 [20.1, 37.0]) vs PBO (all evaluations and timepoints: p<0.001). Image Conclusion(s) Pts reported significantly greater improvements in IBDQ scores at induction and maintenance with miri compared to PBO. Over 75% of pts achieved a clinically meaningful improvement in QoL, as measured by IBDQ response, at the end of the 52 weeks of miri treatment. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Eli Lilly and Company Disclosure of Interest B. Sands Consultant of: Abivax, Amgen, Arena Pharmaceuticals, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Calibr, Celltrion, ClostraBio, Eli Lilly and Company, Enthera, Evommune, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Gossamer Bio, InDex Pharmaceuticals, Innovation Pharmaceuticals, Inotrem, Ironwood Pharmaceuticals, Janssen, Kaleido Biosciences, Kallyope, MiroBio, Morphic Therapeutic, MRM Health, Pfizer, Progenity, Prometheus Therapeutics and Diagnostics, Protagonist Therapeutics, Q32 Bio, Surrozen, Takeda, Teva, TLL Pharmaceutical, USWM Enterprises, and Viela Bio, B. Feagan Shareholder of: Gossamer Bio, Consultant of: AbbVie, AdMIRx, AgomAb Therapeutics, Akebia Therapeutics, Alivio Therapeutics, Allakos, Amgen, Applied Molecular Transport, Arena Pharmaceuticals, Avir Pharma, Azora Therapeutics, Boehringer Ingelheim, Boston Scientific, Celgene/Bristol Myers Squibb, Connect BioPharma, Cytoki Pharma, Disc Medicine, Ecor1 Capital, Eli Lilly and Company, Equillium, Everest Clinical Research, F. Hoffmann-La Roche, Ferring Pharmaceuticals, Galapagos NV, Galen/Atlantica, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, Glenmark Pharmaceuticals, Gossamer Bio, HotSpot Therapeutics, Imhotex, ImmuNext, InDex Pharmaceuticals, Intact Therapeutics, Janssen, Japan Tobacco, Kaleido Biosciences, Leadiant Biosciences, Millennium Pharmaceuticals, MiroBio, Morphic Therapeutics, Mylan, Novartis, OM Pharma, Origo Biopharma, Otsuka, Pandion Therapeutics, Pfizer, Progenity, Prometheus Therapeutics and Diagnostics, PTM Therapeutics, Q32 Bio, Rebiotix, RedHill, Biopharma, Redx Pharma, Sandoz, Sanofi, Seres Therapeutics, Surrozen, Takeda, Teva, Thelium Therapeutics, Theravance Biopharma, TiGenix, Tillotts Pharma AG, UCB Pharma, VHsquared, Viatris, Ysios Capital, and Zealand Pharma, T. Gibble Employee of: Eli Lilly and Company, K. Traxler Employee of: Eli Lilly and Company, N. Morris Employee of: Eli Lilly and Company, X. Li Employee of: Eli Lilly and Company, S. Schreiber Grant / Research support from: personal fees and/or travel support from: AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly and Company, Dr. Falk Pharma, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos NV, Gilead Sciences, I-MAB Biopharma, Janssen, Merck Sharp & Dohme, Mylan, Novartis, Pfizer, Protagonist Therapeutics, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Theravance Biopharma, and UCB Pharma, V. Jairath Consultant of: AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly and Company, Ferring Pharmaceuticals, Flagship Pioneering, Fresenius Kabi, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Pandion Therapeutics, Pendopharm, Pfizer, Protagonist Therapeutics, Reistone Biopharma, Roche, Sandoz, Second Genome, Shire, Takeda, Teva, Topivert, Ventyx Biosciences, and Vividion Therapeutics, A. Armuzzi Consultant of: AbbVie, Allergan, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Gilead Sciences, Janssen, Merck Sharp & Dohme, Mylan, Novartis, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, Takeda, and TiGenix, J. Jones: None Declared

BackgroundImprovement in health-related quality of life (HRQoL) is a key goal of psoriatic arthritis (PsA) therapy.[1,2]Here, we assess whether early clinical response predicts long-term improvement in HRQoL for patients (pts) with PsA and inadequate response to 1–2 tumour necrosis factor inhibitors (TNFi-IR).ObjectivesAssess the association between early clinical response across various PsA domains and HRQoL at Week (W)48, as well as identify baseline (BL) characteristics that could predict early response in guselkumab (GUS)-treated TNFi-IR PsA pts in the Phase 3b COSMOS trial.MethodsIn the randomized controlled COSMOS trial (NCT03796858),[3]adults with active PsA (swollen/tender joint counts [SJC/TJC] each ≥3) and TNFi-IR were randomized 2:1 to receive subcutaneous injections of either GUS 100 mg (at W0, W4, then every 8 weeks through W44) or placebo (at W0, W4, W12, W20, followed by GUS at W16 [early escape] or at W24 [planned], W28, W36, W44). Only pts randomized to GUS were included in this analysis. Long-term improvements in HRQoL were defined as changes from BL to W48 in 36-item short-form survey (SF-36) physical and mental component summary (PCS and MCS) and Dermatology Life Quality Index (DLQI) scores. Early clinical response was defined as achievement of the following criteria at W4 or W8: American College of Rheumatology (ACR)20, pt pain on a visual analogue scale (VAS) ≤15,SJC ≤1, skin VAS ≤20, and health assessment questionnaire – disability index.(HAQ-DI) ≤0.5. In addition, Psoriasis Area and Severity Index (PASI) ≤1 was considered at W16 – the earliest PASI assessment. Analyses were restricted to pts not meeting the respective early response criteria at BL. Long-term HRQoL improvements were compared between pts achieving vs not achieving early response criteria by means of Student’s.t-test and by multivariate linear regression models adjusting for demographic and BL pt disease characteristics. Results from the multivariate linear regression analyses are presented here. Demographic and BL pt disease characteristics predicting early clinical response were investigated using multivariate logistic regression.ResultsOverall, 189 pts were randomized to GUS, with a mean age of 49.1 years, and 45.5% were male. Among pts not meeting the respective early response criteria at BL, GUS led to.2.7–19.0% and 4.3–38.4% of pts achieving one of the clinical responses of interest as early as W4 and W8, respectively. SF-36 PCS improvement from BL to W48 was significantly associated with ACR20 response, SJC ≤1 and HAQ-DI ≤0.5 achievement at W4 as well as at W8. There were no significant findings for SF-36 MCS. DLQI improvement from BL to W48 was significantly associated with ACR20 and skin VAS ≤20 at W8 (Figure 1). Improvements in SF-36 PCS, SF-36 MCS and DLQI at W48 were all significantly associated with achievement of PASI ≤1 at W16. Multivariate logistic regression identified significant (P<0.05) associations between males and early clinical response at W8 (ACR20: odds ratio [OR]=1.98; HAQ-DI ≤0.5: OR=3.71), BL SJC and.SJC ≤1 at W8 (OR=0.84), BL HAQ-DI and HAQ-DI ≤0.5 at W8 (OR=0.23), and BL skin VAS and skin VAS ≤20 at W8 (OR=0.98).ConclusionFor pts receiving GUS, ACR20 response at W4 and W8 was positively associated with SF-36 PCS improvement from BL to W48, and also at W8 with DLQI improvement from BL to W48. Therefore, early clinical response is relevant for HRQoL improvements over time. These results may help in shared decision-making processes.References[1]Gossec Let al Ann Rheum Dis2020;79:700–12[2]Coates LCet al. Nat Rev Rheumatol2022;18:465–79[3]Coates LCet al Ann Rheum Dis2022;81:359–69Acknowledgements:NIL.Disclosure of InterestsLaure Gossec Consultant of: AbbVie, Amgen, BMS, Celltrion, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Grant/research support from: Sandoz, UCB, Daniel Aletaha Speakers bureau: Abbvie, Gilead, Galapagos, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Consultant of: Abbvie, Gilead, Galapagos, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Grant/research support from: Abbvie, Gilead, Galapagos, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi, Philipp Sewerin Speakers bureau: AXIOM Health, Amgen, AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Chugai Pharma Marketing Ltd./ Chugai Europe, Deutscher Psoriasis-Bund, Gilead Sciences, Hexal Pharma, Janssen-Cilag, Johnson & Johnson, Lilly/ Lilly Europe/ Lilly Global, medi-login, Mediri GmbH, Novartis Pharma, Onkowissen GmbH, Pfizer, Roche Pharma, Rheumazentrum Rhein-Ruhr, Sanofi-Genzyme, Spirit Medical Communications, Swedish Orphan Biovitrum, UCB Pharma, Consultant of: AXIOM Health, Amgen, AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Chugai Pharma Marketing Ltd./ Chugai Europe, Deutscher Psoriasis-Bund, Gilead Sciences, Hexal Pharma, Janssen-Cilag, Johnson & Johnson, Lilly/ Lilly Europe/ Lilly Global, medi-login, Mediri GmbH, Novartis Pharma, Onkowissen GmbH, Pfizer, Roche Pharma, Rheumazentrum Rhein-Ruhr, Sanofi-Genzyme, Spirit Medical Communications, Swedish Orphan Biovitrum, UCB Pharma, Grant/research support from: AXIOM Health, Amgen, AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Chugai Pharma Marketing Ltd./ Chugai Europe, Deutscher Psoriasis-Bund, Gilead Sciences, Hexal Pharma, Janssen-Cilag, Johnson & Johnson, Lilly/ Lilly Europe/ Lilly Global, medi-login, Mediri GmbH, Novartis Pharma, Onkowissen GmbH, Pfizer, Roche Pharma, Rheumazentrum Rhein-Ruhr, Sanofi-Genzyme, Spirit Medical Communications, Swedish Orphan Biovitrum, UCB Pharma, Alen Zabotti Speakers bureau: AbbVie, Novartis, Janssen, Lilly, UCB, Amgen, Paid instructor for: AbbVie, Novartis, UCB, Filip van den Bosch Consultant of: AbbVie, Amgen, Eli Lilly, Galapagos, Janssen, Moonlake, Novartis, Pfizer and UCB, Michela Efficace Shareholder of: Janssen Pharmaceutical Companies of Johnson and Johnson, Employee of: Janssen Pharmaceutical Companies of Johnson and Johnson, Frederic Lavie Shareholder of: Johnson & Johnson, Abbvie, Employee of: The Janssen Pharmaceutical Companies of Johnson & Johnson, Miriam Zimmermann Employee of: Janssen Pharmaceutical Companies of Johnson and Johnson, Mohamed Sharaf Employee of: Janssen Pharmaceutical Companies of Johnson and Johnson, Iain McInnes Speakers bureau: Abbvie, Consultant of: Amgen Abbvie, Astra Zeneca, GSK, Lilly, Sanofi, Evelo, Compugen, Cabaletta, UCB, Novartis, BMS, Causeway Therapeutics, Gilead, Moonlake, Pfizer, Janssen, Grant/research support from: Amgen, AstraZeneca, BMS, Lilly Novartis, Janssen, GSK, UCB, Pfizer.

Background:EULAR guidelines recommend a treat-to-target approach focusing on reducing inflammation to prevent joint damage, physical disability, and mortality.1However, patients consider reduction in pain and fatigue, along with maintenance of physical function, and improvement in health-related quality of life (HRQoL) important areas for improvement with RA treatment.2In the FINCH 2 study, filgotinib (FIL)—a potent, selective, oral small molecule Janus kinase 1 inhibitor—in combination with conventional synthetic (cs)DMARD therapy significantly improved the signs and symptoms of rheumatoid arthritis (RA) in patients with an inadequate response to a biologic (b)DMARD compared with placebo (PBO).3In addition, patients experienced significant improvements in HAQ-DI at week (W)12 and W24 with FIL 100 mg (p <0.001, p = 0.003) or 200 mg (p <0.001 for both) compared with PBO.3Objectives:To evaluate the rate and magnitude of change in patient-reported outcomes (PROs) from FINCH 2 assessing pain, HRQoL, and fatigue.Methods:Patients in this double-blind, randomised study (NCT02873936) received FIL 200 mg, FIL 100 mg, or PBO while continuing csDMARD therapy. PROs were collected prospectively on day 1 and at the W2, W4, W8, W12, W14, W16, W20, and W24 visits for assessment of pain (VAS pain scale) and on day 1 and at W4, W12, and W24 for assessment of fatigue (FACIT-Fatigue) and HRQoL (SF-36). Changes from baseline for each PRO at each time point up to W24 were analysed longitudinally using a mixed-effects model for repeated measures. P values for the difference between each FIL arm and PBO at each time point were calculated.Results:Among the 448 patients randomised and treated (FIL 200 mg, n = 147; FIL 100 mg, n = 153; PBO, n = 148) 381 (85.0%) completed the study. Baseline mean (SD) VAS pain scale was 67 (21.0), SF-36 physical component summary (PCS) was 31.1 (7.89), SF-36 mental component summary (MCS) was 44.3 (11.6), and FACIT-Fatigue score was 24.4 (11.6); baseline values did not vary between treatment groups. Significantly greater improvements in VAS pain scores began at W2 and were maintained through W24 for patients who received either dose of FIL vs PBO (Fig 1A). FIL also significantly improved patients’ fatigue at W4, W12, and W24 compared with PBO for those receiving 200 mg doses, and at W4 and W12 for those receiving 100 mg doses (Fig 1B). HRQoL related to physical functioning (SF-36 PCS) was significantly enhanced at W4, W12, and W24 with both doses of FIL as compared with PBO (Fig 2A). Improvements to mental-health-related QoL (SF-36 MCS) were reported for FIL as early as W4 and maintained through W24, with statistically significant improvements at W4 and W12 for FIL 200 mg vs PBO (Fig 2B).Conclusion:In a patient population with refractory disease that had inadequate response to prior bDMARDs and had significant disease at baseline, FIL treatment—coadministered with csDMARD therapy—was able to provide rapid and sustained improvements in key measures of pain, HRQoL, and fatigue as reported by patients.References:[1]Smolen, et al.Ann Rheum Dis. 2017;76:960–77.[2]Fautrel, et al.Rheumatol Int.2018;38:935–47.[3]Genovese, et al.JAMA. 2019;322(4):315–25.Disclosure of Interests:David Walker Grant/research support from: Gilead, Consultant of: Gilead, Lilly, Pfizer, Roche, Speakers bureau: Lilly, Pfizer, Roche, Tsutomu Takeuchi Grant/research support from: AbbVie, Asahikasei Pharma Corp., Astellas Pharma, Inc., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Nipponkayaku Co. Ltd., Shionogi & Co., Ltd., Takeda Pharmaceutical Co., Ltd., UCB Japan, Consultant of: Astellas Pharma, Inc., Chugai Pharmaceutical Co, Ltd., Eli Lilly Japan,, Speakers bureau: Abbvie, AYUMI Pharmaceutical Corp., Bristol-Myers Squibb, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan, Gilead Sciences, Inc., Mitsubishi-Tanabe Pharma Corp., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd, Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Shangbang Rao Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., I-Heng Lee Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Background:Filgotinib (FIL), an oral, potent, selective JAK-1 inhibitor, provided statistically significant and clinically meaningful improvement in rheumatoid arthritis (RA) signs and symptoms, physical function, radiographic progression, and quality of life in a comprehensive clinical program of 4 phase 3 (FINCH 1–4;NCT02889796,NCT02873936,NCT02886728,NCT03025308) and 3 phase 2 (DARWIN 1–3;NCT01668641,NCT01894516,NCT02065700) trials in patients (pts) with early and biologic-refractory RA.1–3Objectives:To assess long-term safety of FIL.Methods:Treatment-emergent adverse events (TEAEs) from the FIL clinical program were integrated and presented for pts receiving FIL 200 mg or FIL 100 mg QD (including pts who transitioned to FIL from placebo [PBO], methotrexate [MTX], adalimumab [ADA], or another dose of FIL) as well as pts receiving PBO, MTX, and ADA across all 7 studies. Exposure-adjusted incidence rates (EAIRs) per 100 patient-years (PY) were calculated for adverse events (AEs) of interest per treatment. Incidence was total number of pts with events, and PY exposure was time between first and last doses. Major adverse cardiovascular events (MACE) and venous thromboembolism (VTE) were centrally adjudicated by an independent committee.Results:Across the 7 trials, 4057 pts with RA (2227 pts FIL 200 mg; 1600 pts FIL 100 mg) received >1 dose of treatment for 5493 total PY of exposure (3079.2 PY FIL 200 mg; 1465.3 PY FIL 100 mg) (Table). EAIRs of serious AEs and TEAEs leading to death in pts receiving FIL were comparable to those for PBO, ADA, or MTX, with no dose-dependent effect (Figure 1). EAIR for herpes zoster (HZ), serious, and opportunistic infections are shown in Figure 2. EAIR for HZ were low overall, but numerically slightly higher for FIL relative to PBO, ADA, and similar to MTX. Serious infection EAIRs were comparable between pts receiving FIL 100 mg and ADA, and numerically slightly lower for FIL 200 mg and MTX. Rates of opportunistic infections (including active tuberculosis) were low overall; EAIR for FIL doses were comparable to placebo and numerically lower than ADA or MTX. Rates of MACE and VTE were numerically lower for FIL relative to PBO (Figure 1). Malignancies, including nonmelanoma skin cancer, were rare overall, and rates were low in pts receiving FIL (Figure 1).Table.Total exposure to study treatments pooled from 7 studiesNumber of patientsPatient-years of exposureFIL 200 mg22273079.2FIL 100 mg16001465.3ADA325290.1MTX416356.2PBO781302.4Patients could contribute to >1 treatment group.ADA, adalimumab; FIL, filgotinib; MTX, methotrexate; PBO, placebo.Conclusion:In this integrated analysis, FIL was well-tolerated, and no new safety concerns were identified. No clinically meaningful dose-dependent safety effects were observed. MACE and VTE were uncommon. Serious infections rates were low; HZ reactivation was infrequent. Safety results were consistent with selective JAK-1 inhibition and highlight the favourable safety and tolerability of FIL in patients with RA.References:[1]Genovese, et al.JAMA2019;322(4):315–25.[2]Westhovens, et al.Ann Rheum Dis2017;76:998–1008.[3]Kavanaugh, et al.Ann Rheum Dis2017;76:1009–19.Disclosure of Interests:Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Tsutomu Takeuchi Grant/research support from: Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Takeda Pharmaceutical Company Ltd, UCB Pharma, Shionogi & Co., Ltd., Mitsubishi-Tanabe Pharma Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co. Ltd., Consultant of: Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., Eli Lilly Japan KK, Speakers bureau: AbbVie GK, Eisai Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, AYUMI Pharmaceutical Corp., Eisai Co., Ltd, Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Novartis Pharma K.K., Pfizer Japan Inc., Sanofi K.K., Dainippon Sumitomo Co., Ltd., Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim,,Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Franziska Matzkies Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Lei Ye Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Deyuan Jiang Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ying Guo Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Beatrix Bartok Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Robin Besuyen Shareholder of: Galapagos, Employee of: Galapagos, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB

Abstract Background Mirikizumab (miri) improved symptom control in a Phase 3, multicenter, randomized, double-blind, parallel, placebo-controlled induction study at Week (W)12, in patients (pts) with moderately-to-severely active ulcerative colitis (UC; LUCENT-1). Purpose This analysis assessed sustained symptom control during the maintenance phase through W40 (W52 of continuous therapy), among pts who were induced into clinical response with miri. Method During the 40W maintenance study (LUCENT-2), pts (N=544) who achieved clinical response to miri 300mg Q4W by W12 of induction, were re-randomized 2:1 to subcutaneous (SC) miri 200mg (n=365) or PBO Q4W (n=179). We evaluated sustained control of stool frequency (SF), rectal bleeding (RB), bowel movement urgency (BU) and abdominal pain (AP). The proportion of pts achieving SF Remission (defined as SF=0, or SF=1 with a ≥1-point decrease from induction baseline [BL]), RB Remission (RB=0), Symptomatic Remission (both SF and RB Remission), Stable Maintenance of Symptomatic Remission (defined as pts in Symptomatic Remission for at least 7 out of 9 visits from W4 to W36 and also at Week 40 among pts in Symptomatic Remission and Clinical Response at the end of LUCENT-1), and AP Improvement (Numeric Rating Scale [NRS] pain score ≥30% improvement from BL in pts with baseline AP NRS ≥3) were assessed. BU NRS change from baseline, and the proportion of pts achieving BU Remission (NRS 0 or 1 in pts with BU NRS ≥3 at baseline) were evaluated. Result(s) A greater proportion of miri-treated pts achieved SF Remission, RB Remission and Symptomatic Remission compared to PBO at W40 (Table), with significant differences observed from W8 of LUCENT-2 (p=0.042; p=0.004; p=0.036, respectively) and maintained through W40. Miri-treated pts had a significantly higher percentage of Stable Maintenance of Symptomatic Remission (p&lt;0.001). Pts in the miri-treatment group had a significantly greater mean reduction in BU NRS change from induction BL starting at W12 (p=0.034) onwards compared to PBO (Table). Pts assigned to miri accrued an additional 13.6 percentage-point benefit in BU Remission during the first 8W of maintenance therapy and achieved a significant greater improvement at W40 compared to PBO (p&lt;0.001, Table). Similarly, AP was significantly improved for the miri-treated group starting at W16 (p=0.034) onwards compared to PBO. Image Conclusion(s) Miri provides sustained control of UC symptoms including BU, RB, and SF compared to PBO in pts with moderately to severely active UC. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Eli Lilly and Company Disclosure of Interest A. Dignass Consultant of: AbbVie, Abivax, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb (Celgene), Celltrion, Dr. Falk Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Pharmacosmos, Roche, Sandoz/Hexal, Takeda, Tillotts Pharma AG, and Vifor Pharma; has received lecture fees or honoraria from: AbbVie, Amgen, Bristol Myers Squibb, Dr. Falk Pharma, Ferring Pharmaceuticals, Galapagos, High5Md, Janssen, Materia, Merck Sharp & Dohme, Pfizer, Sandoz, Takeda, Tillotts Pharma AG, and Vifor Pharma, S. Danese Consultant of: AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Eli Lilly and Company, Enthera, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Inotrem, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Mundipharma, Mylan, Pfizer, Roche, Sandoz Sublimity, Takeda, TiGenix, UCB Pharma, and Vifor Pharma, Speakers bureau of: AbbVie, Amgen, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Mylan, Pfizer, and Takeda, K. Matsuoka Grant / Research support from: AbbVie, EA Pharma, JIMRO, Kissei Pharmaceutical, Kyowa Kyorin, Mitsubishi Tanabe, Mochida Pharmaceutical, and Zeria Pharmaceutical Nippon; lecture fees from: AbbVie, EA Pharma, JIMRO, Kissei Pharmaceutical, Kyowa Kyorin, Mitsubishi Tanabe, Mochida Pharmaceutical, Takeda, and Zeria Pharmaceutical Nippon, M. Ferrante Grant / Research support from: AbbVie, Amgen, Biogen, Janssen Cilag, Pfizer, Takeda, and Viatris, Consultant of: AbbVie, Boehringer Ingelheim, Celltrion, Eli Lilly and Company, Janssen Cilag, Medtronic, Merck Sharp & Dohme, Pfizer, Regeneron, Sandoz, Takeda, and Thermo Fisher Scientific, Speakers bureau of: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celltrion, Dr. Falk Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Janssen, Lamepro, Medtronic, Merck Sharp & Dohme, Mylan, Pfizer, Samsung Bioepis, Sandoz, Takeda, and Thermo Fisher Scientific, M. Long Consultant of: AbbVie, Bristol Myers Squibb, Calibr, Eli Lilly and Company, Genentech, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda, TARGET PharmaSolutions, and Theravance Biopharma, I. Redondo Employee of: Eli Lilly and Company, T. Gibble Employee of: Eli Lilly and Company, R. Moses Employee of: Eli Lilly and Company, X. Li Employee of: Eli Lilly and Company, N. Morris Employee of: Eli Lilly and Company, C. Milch Employee of: Former employee, was employed at Eli Lilly and Company at the time of study, M. Abreu Grant / Research support from: Pfizer, Prometheus Biosciences, and Takeda, Consultant of: AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly and Company, Gilead Sciences, Janssen, Microba Life Sciences, Prometheus Biosciences, UCB Pharma, and WebMD, Speakers bureau of: Alimentiv, Intellisphere LLC (HCP Live Institutional Perspectives in GI), Janssen, Prime CME, and Takeda, J. Jones: None Declared

Abstract Background Mirikizumab (miri), an anti-IL23/p19 monoclonal antibody, demonstrated efficacy compared with placebo (PBO) in the Phase 3, multicentre, randomized, double-blind LUCENT-1 induction study in patients with moderately to severely active ulcerative colitis (UC, NCT03518086). Purpose This analysis assessed early onset of symptomatic improvement and symptomatic control during induction. Method During the 12-week (W) induction study, 1162 adult patients (pts) with inadequate response, loss of response, or were intolerant to conventional therapy or biologic or tofacitinib therapy for UC, received miri IV Q4W (N=868) or PBO (N=294). We evaluated improvement for symptoms of stool frequency (SF), rectal bleeding (RB) and bowel movement urgency (BU), abdominal pain and fatigue. BU Numeric Rating Scale (NRS) change from baseline (BL), BU Clinical Meaningful Improvement (CMI), BU Remission, Fatigue NRS change from BL, Abdominal Pain Improvement, as well as SF Remission, RB Remission, Symptomatic Response and Symptomatic Remission were assessed. Result(s) As early as W2, miri-treated pts achieved a significantly greater reduction in RB subscores (p=0.001) and in SF subscores (p=0.035). From W2 and W4, a significantly greater percentage achieved SF Remission and RB Remission, respectively compared to PBO. A significantly greater percentage of miri-treated pts achieved Symptomatic Response compared to PBO from W2 (p=0.003) and of Symptomatic Remission compared with PBO from W4 (p&lt;0.001). Miri-treated pts showed a significantly greater mean reduction in BU NRS scores as early as W2 compared to PBO (p=0.004). From W4, a significantly greater percentage of miri-treated pts achieved BU CMI versus PBO (p=0.044). From W7 onwards, a significantly greater percentage achieved BU Remission (p=0.002). The pts showed a significantly greater mean reduction in Fatigue NRS scores from W2 compared to PBO (p=0.014). As early as W4, a significant reduction of at least 30% in Abdominal Pain NRS score from BL was observed in the miri-treated pts compared with PBO (p=0.007). At W12, a significantly greater proportion of miri-treated pts achieved Symptomatic Response, Symptomatic Remission, RB Remission, SF Remission, BU change from BL, BU CMI and Remission, as well as Fatigue and Abdominal Pain Improvement, compared to PBO (Table). Image Conclusion(s) Miri provides rapid control of UC symptoms, including BU and fatigue, as early as W2 compared with PBO in pts with moderately to severely active UC. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Eli Lilly and Company Disclosure of Interest S. Danese Consultant of: AbbVie, Alimentiv, Allergan, Amgen, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr. Falk Pharma, Eli Lilly and Company, Enthera, Ferring Pharmaceuticals, Gilead Sciences, Hospira, Inotrem, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Mundipharma, Mylan, Pfizer, Roche, Sandoz Sublimity, Takeda, TiGenix, UCB Pharma, and Vifor Pharma, Speakers bureau of: AbbVie, Amgen, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Mylan, Pfizer, and Takeda, A. Dignass Consultant of: AbbVie, Abivax, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb (Celgene), Celltrion, Dr. Falk Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, Gilead Sciences, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Pharmacosmos, Roche, Sandoz/Hexal, Takeda, Tillotts Pharma AG, and Vifor Pharma, Speakers bureau of: AbbVie, Amgen, Bristol Myers Squibb, Dr. Falk Pharma, Ferring Pharmaceuticals, Galapagos, High5Md, Janssen, Materia, Merck Sharp & Dohme, Pfizer, Sandoz, Takeda, Tillotts Pharma AG, and Vifor Pharma, K. Matsuoka Grant / Research support from: AbbVie, EA Pharma, JIMRO, Kissei Pharmaceutical, Kyowa Kyorin, Mitsubishi Tanabe, Mochida Pharmaceutical, and Zeria Pharmaceutical Nippon, Speakers bureau of: AbbVie, EA Pharma, JIMRO, Kissei Pharmaceutical, Kyowa Kyorin, Mitsubishi Tanabe, Mochida Pharmaceutical, Takeda, and Zeria Pharmaceutical Nippon, M. Ferrante Grant / Research support from: AbbVie, Amgen, Biogen, Janssen Cilag, Pfizer, Takeda, and Viatris, Consultant of: AbbVie, Boehringer Ingelheim, Celltrion, Eli Lilly and Company, Janssen Cilag, Medtronic, Merck Sharp & Dohme, Pfizer, Regeneron, Sandoz, Takeda, and Thermo Fisher Scientific, Speakers bureau of: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celltrion, Dr. Falk Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Janssen, Lamepro, Medtronic, Merck Sharp & Dohme, Mylan, Pfizer, Samsung Bioepis, Sandoz, Takeda, and Thermo Fisher Scientific, M. Long Consultant of: AbbVie, Bristol Myers Squibb, Calibr, Eli Lilly and Company, Genentech, Janssen, Pfizer, Prometheus Biosciences, Roche, Takeda, TARGET PharmaSolutions, and Theravance Biopharma, I. Redondo Employee of: Eli Lilly and Company, T. Gibble Employee of: Eli Lilly and Company, R. Moses Employee of: Eli Lilly and Company, N. Morris Employee of: Eli Lilly and Company, X. Li Employee of: Eli Lilly and Company, C. Milch Employee of: former employee, was employed at Eli Lilly and Company at the time of study, M. Abreu Grant / Research support from: Pfizer, Prometheus Biosciences, and Takeda, Consultant of: AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Eli Lilly and Company, Gilead Sciences, Janssen, Microba Life Sciences, Prometheus Biosciences, UCB Pharma, and WebMD, Speakers bureau of: Alimentiv, Intellisphere LLC (HCP Live Institutional Perspectives in GI), Janssen, Prime CME, and Takeda, J. Jones: None Declared

Abstract Background Moderate to severe ulcerative colitis (UC) exerts a significant burden on patients’ lives. Patients with UC report that bowel urgency has a substantial negative impact on their quality of life and psychosocial functioning, however, this symptom is missing from most disease activity indices. Purpose The Communicating Needs and Features of IBD Experiences (CONFIDE) study aims to increase understanding of the impact of symptoms, including bowel urgency, on the lives of patients (pts) with moderate to severe UC and Crohn’s disease in the United States (US), Europe (EUR), and Japan. These data focus on pts in the US and EUR. Method Online, quantitative, cross-sectional surveys of pts with moderate to severe UC were conducted in the US and EUR (France, Germany, Italy, Spain, and UK). Data included pt perspectives on their UC symptoms and the impact on their daily lives. Moderate to severe UC was defined based on treatment, steroid use, and/or hospitalization history. Descriptive statistics summarise the data. Result(s) 200 US pts (62% male, mean age 40.4 years) and 556 EUR pts (57% male, mean age 38.9 years) completed the survey, with 77% and 54% currently receiving advanced therapies (biologic or novel oral therapy), respectively. The top 3 symptoms currently (past month) experienced by US and EUR pts were diarrhoea (63% and 50%), bowel urgency (47% and 30%) and increased stool frequency (39% and 30%). In past 3 months, pts who have ever experienced bowel urgency or urge incontinence reported bowel urgency (93% US, 89% EUR) and urge incontinence (86% US, 71% EUR) at least once a month (Table). 69% and 65% of all US and EUR pts, respectively, reported wearing a diaper/pad/protection at least once a month in the past 3 months due to fear/anticipation of urge incontinence. For pts receiving advanced therapies, similar patterns were observed. Among both US and EUR pts, the most common UC-related reasons for declining participation in social events were bowel urgency (43% and 30%) and fear of urge incontinence (40% and 32%). Similarly, the most common reasons for declining participation in work/school and sports/physical exercise were bowel urgency and fear of urge incontinence. Image Conclusion(s) Bowel urgency, which was the second-most frequently reported symptom, has an extensive impact on the lives of pts with moderate to severe UC. In this younger pt population, including pts receiving advanced therapies, almost two thirds of US and EUR pts reported wearing diapers/pads/protection at least once a month in the past 3 months due to fear/anticipation of urge incontinence. Both US and EUR pts reported bowel urgency and fear of urge incontinence as the top reasons for declining participation in social events, work/school, and sports/physical exercise. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Eli Lilly and Company Disclosure of Interest S. Schreiber Grant / Research support from: personal fees and/or travel support from: AbbVie, Amgen, Arena Pharmaceuticals, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Eli Lilly and Company, Dr. Falk Pharma, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos NV, Gilead Sciences, I-MAB Biopharma, Janssen, Merck Sharp & Dohme, Mylan, Novartis, Pfizer, Protagonist Therapeutics, Provention Bio, Roche, Sandoz/Hexal, Shire, Takeda, Theravance Biopharma, and UCB Pharma, A. Bleakman Employee of: Eli Lilly and Company, M. Dubinsky Shareholder of: Trellus Health, Grant / Research support from: AbbVie, Janssen, Pfizer, and Prometheus Biosciences, Consultant of: AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly and Company, F. Hoffmann-La Roche, Genentech, Gilead Sciences, Janssen, Pfizer, Prometheus Therapeutics and Diagnostics, Takeda, and UCB Pharma, D. Rubin Grant / Research support from: Takeda, Consultant of: AbbVie, Allergan, AltruBio, American College of Gastroenterology, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene/Syneos Health, Cornerstones Health (non-profit), Eli Lilly and Company, Galen/Atlantica, Genentech/Roche, Gilead Sciences, GoDuRn, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen, Materia Prima, Pfizer, Prometheus Therapeutics and Diagnostics, Reistone Biopharma, Takeda, and TechLab, T. Hibi Grant / Research support from: AbbVie, Activaid, Alfresa Pharma, Bristol Myers Squibb, Eli Lilly Japan K.K., Ferring Pharmaceuticals, Gilead Sciences, Janssen Pharmaceutical K.K., JMDC, Nippon Kayaku, Mochida Pharmaceutical, Pfizer Japan, and Takeda, Consultant of: AbbVie, Apo Plus Station, Bristol Myers Squibb, Celltrion, EA Pharma, Eli Lilly and Company, Gilead Sciences, Janssen, Kyorin, Mitsubishi Tanabe Pharma, Nichi-Iko Pharmaceutical, Pfizer, Takeda, and Zeria Pharmaceutical, Speakers bureau of: AbbVie, Aspen Japan K.K., Ferring Pharmaceuticals, Gilead Sciences, Janssen, JIMRO, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, and Takeda, R. Panaccione Grant / Research support from: AbbVie, Ferring Pharmaceuticals, Janssen, Pfizer, and Takeda, Consultant of: Abbott, AbbVie, Alimentiv, Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmo Pharmaceuticals, Eisai, Elan Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Galapagos NV, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Therapeutics, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda, Theravance Biopharma, and UCB Pharma, T. Gibble Employee of: Eli Lilly and Company, C. Kayhan Employee of: Eli Lilly and Company, E. Flynn Employee of: Eli Lilly and Company, C. Sapin Employee of: Eli Lilly and Company, C. Atkinson Consultant of: Eli Lilly and Company in connection with the development of this publication, Employee of: Adelphi Real World, S. Travis Grant / Research support from: AbbVie, BUHLMANN Diagnostics, ECCO, Eli Lilly and Company, Ferring Pharmaceuticals, International Organization for the Study of Inflammatory Bowel Disease, Janssen, Merck Sharp & Dohme, Normal Collision Foundation, Pfizer, Procter & Gamble, Schering-Plough, Takeda, UCB Pharma, Vifor Pharma, and Warner Chilcott, J. Jones: None Declared

BackgroundUp to 40% of patients with psoriasis (PsO) develop psoriatic arthritis (PsA), which can have a significant impact on health-related quality of life (HRQoL)[1]. Among patients with both PsO and PsA (PsO/PsA) who are treated with a biologic agent, individual symptom profiles and response to treatment can vary, with many patients switching biologic agents over their disease course. Whether patient-centred factors, beyond skin clearance, influence biologic switching remains a critical gap in the medical literature.ObjectivesTo evaluate the association of psoriatic disease burden with biologic agent switch among patients with PsO/PsA in a real-world setting.MethodsThis study included data from the CorEvitas PsO Registry, a prospective, multicentre, non-interventional registry that collects data at ~6-month intervals. Biologic therapy initiations by patients with plaque PsO and dermatologist-diagnosed PsA or history of ≥3 PsO Epidemiology Screening Test (PEST) score who initiated a biologic agent at a registry visit and had ≥1 visit in the subsequent 30 months between April 2015 and August 2021 were included in this study. Disease burden at each follow-up visit after biologic initiation was defined by combinations of Psoriasis Area and Severity Index (PASI) level (≤10 vs >10) with Dermatology Life Quality Index (DLQI) level (≤5 vs >5) or patient-reported joint pain (VAS-100) level (<40 vs ≥40)[2]. The outcome of biologic switch, defined as a start of a different biologic agent within 45 days of discontinuing the initial biologic, was assessed at each follow-up visit. Proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) to evaluate associations between disease burden categories and biologic switch, adjusted for age, sex, race, ethnicity, duration of PsO, baseline disease burden category, body mass index (BMI), employment status, number of comorbidities, and treatment history.ResultsThere were 2,580 patient-initiations included in this study. The mean age at patient-initiation was 52 years (Standard Deviation=13) and 52% occurred in females. Over 56% of patient-initiations were obese (BMI≥30), and 27% had at least one comorbidity. Twenty percent of patient-initiations switched biologic agents over 30 months of follow-up after a median (Interquartile Range) of 6.5 (4.6, 12.4) months of treatment. Patients with combined highest skin involvement and impact on HRQoL (PASI>10 & DLQI>5) were 14 times more likely to switch biologic (HR=14.2; 95% CI: 10.7, 18.9) than those with the lowest combined skin involvement and impact on HRQoL (PASI≤10 & DLQI≤5). Patients with DLQI>5 were over five times more likely to switch biologic vs the DLQI≤5 group among patients with PASI≤10 (HR=5.25; 95% CI: 4.23, 6.51) and nearly twice as likely to switch biologic among those with PASI>10 (HR=1.70; 95% CI: 1.06, 2.71). Similarly, patients with joint pain ≥40 had nearly a four times higher likelihood of switching vs the pain <40 group among those with PASI≤10 (HR=3.78; 95% CI: 2.91, 4.92) and tended to be more likely to switch biologic in patients with PASI>10 (HR=1.35; 95% CI: 0.79, 2.33).ConclusionPatients with PsO/PsA treated in a real-world clinical setting with more significant disease burden due to impaired HRQoL (DLQI and joint pain) after initiation were more likely to switch biologic agents, regardless of PASI level. These findings suggest that patient-centred factors, as well as skin clearance, have an important impact on the occurrence of biologic agent switch and the management of patients with PsO/PsA.References[1]Mease P, et al. Drugs. 2014;74(4):423-441;[2] Imafuku S, et al. J Dermatol Sci. 2021;101(3):185-193.Acknowledgements:NIL.Disclosure of InterestsPhilip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Acelyrin, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma, UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, UCB Pharma, Eric Jones: None declared, Adam Sima: None declared, Silky Beaty Employee of: UCB Pharma, Robert Low Employee of: UCB Pharma, Braulio Gomez Employee of: UCB Pharma, Marie Gurrola: None declared, Mark Lebwohl Consultant of: Aditum Bio, Almirall, AltruBio Inc., AnaptysBio, Arcutis, Inc., Arena Pharmaceuticals, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Brickell Biotech, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, CorEvitas, Dermavant Sciences, Dr. Reddy’s Laboratories, Evelo Biosciences, Evommune, Inc., Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, Verrica, Grant/research support from: Abbvie, Amgen, Arcutis, Avotres Therapeutics, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, UCB Pharma.

In this interview, Professor Moshe Szyf speaks with Storm Johnson, Commissioning Editor for Epigenomics, on his work to date in the field of social epigenetics. Szyf received his PhD from the Hebrew University and did his postdoctoral fellowship in genetics at Harvard Medical School, joined the Department of Pharmacology and Therapeutics at McGill University in Montreal in 1989 and is a fellow of the Royal Society of Canada and the Academy of Health Sciences of Canada. He is the founding codirector of the Sackler Institute for Epigenetics and Psychobiology at McGill and is a Fellow of the Canadian Institute for Advanced Research Experience-Based Brain and Biological Development program. Szyf was the founder of the first pharma to develop epigenetic pharmacology, Methylgene Inc., and the journal Epigenetics. The Szyf lab proposed two decades ago that DNA methylation is a prime therapeutic target in cancer and other diseases and postulated and provided the first set of evidence that the social environment early in life can alter DNA methylation, launching the emerging field of social epigenetics.

Background:In the SELECT-PsA 1 study, through 24 weeks (wks), once daily upadacitinib 15 mg (UPA15) and 30 mg (UPA30) showed improvements in musculoskeletal symptoms, psoriasis, physical function, pain, fatigue, and quality of life, as well as inhibition of radiographic progression in patients (pts) with psoriatic arthritis (PsA) and inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (DMARD).1Objectives:To report the efficacy and safety of UPA vs adalimumab (ADA) up to 56 wks from the ongoing long-term extension of SELECT-PsA 1.Methods:Pts received UPA15 or UPA30, ADA 40mg every other wk for 56 wks, or PBO through wk 24 switched thereafter to either UPA15 or UPA30 until wk 56. Efficacy endpoints as listed and defined in the Table 1 were analyzed at wk 56. Results for binary endpoints are based on non-responder imputation analysis; treatments were compared using the Cochran-Mantel-Haenszel test. Results for non-radiographic continuous endpoints are based on mixed model repeated measures model based on as observed data. Radiographic endpoints were analyzed based on linear extrapolation. Treatment-emergent adverse events (TEAEs) per 100 pt years (PY) were summarized for pts who received ≥1 dose of study drug.Table 1.Efficacy Endpoints at Week 56EndpointPBO → UPA15PBO → UPA30UPA15UPA30ADAACR20, %73.074.174.474.7#68.5ACR50, %54.560.459.7*60.5#51.3ACR70, %29.935.840.6*43.7#31.2Minimal Disease Activity, %29.435.844.847.3#39.6PASI75a, %58.360.265.463.361.1PASI90a, %41.753.749.149.546.9PASI100a, %22.338.934.639.531.3Resolution of enthesitis by Leeds Enthesitis Index b, %38.145.559.358.154.0Resolution of dactylitis by Leeds Dactylitis Index c, %47.759.075.074.874.0Δ from BL in Bath Ankylosing Spondylitis Disease Activity Index d-3.1-3.1-3.3-3.2-2.8Δ from BL in modified total Sharp/van der Heijde Score (mTSS)0.44e-0.05†0.02‡-0.06* and †, p≤0.05; for UPA15 vs ADA and PBO, respectively; # and ‡, p≤0.05; for UPA30 vs ADA and PBO, respectively.a for pts with psoriasis affecting ≥3% of body surface area at BL. b for pts with LEI >0 at BL. c for pts with LDI >0 at BL. d for pts with psoriatic spondylitis at BL. epooled PBO.ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; ADA, adalimumab; BL, baseline; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; PBO, placebo; pts, patients; UPA, upadacitinib.Results:Of 1704 pts who received ≥1 dose of study drug, 1419 (83.2%) completed 56 wks of treatment on study drug. Across all treatment groups, the proportions of pts who had achieved ACR20/50/70, MDA, PASI75/90/100, resolution of enthesitis, and resolution of dactylitis were maintained or further improved from wk 241 through wk 56; these proportions were generally greater for pts originally randomized to UPA vs ADA (Table 1). At wk 56, mean change from BL in mTSS was similar with UPA15, UPA30, and ADA. Improvements in pts who switched from PBO to UPA were generally similar to those originally randomized to UPA at wk 56. Through wk 56, the rates of TEAEs and serious AEs, including serious infections, were similar in the UPA15 and ADA arms and higher with UPA30 (Figure 1). The rate of herpes zoster was higher with UPA vs ADA in a dose-dependent manner. Malignancies were reported at similar rates among all treatment groups. Adjudicated venous thromboembolic events and major adverse cardiovascular events were reported in all groups with comparable rates. Two deaths were reported with UPA15, 2 with UPA30, and 1 with ADA; 1 death was reported with PBO during the 24-wk PBO-controlled period.Conclusion:Efficacy responses were maintained or further improved with UPA15 and UPA30 over 56 wks and were numerically higher vs ADA. The inhibition of radiographic progression was maintained at wk 56 and was similar with UPA and ADA. At wk 56, improvements in efficacy were observed in pts who switched from PBO to UPA. No new safety findings were observed with longer exposure to UPA.References:[1]McInnes IB et al. Ann Rheum Dis, 2020; 79:12Figure 1Acknowledgements:AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea, PhD of AbbVie Inc.Disclosure of Interests:Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, UCB Pharma, Koji Kato Shareholder of: AbbVie, Employee of: AbbVie, Marina Magrey Consultant of: UCB, Novartis, Eli Lilly, Pfizer and Janssen, Grant/research support from: Amgen, AbbVie, and UCB Pharma, Joseph F. Merola Consultant of: Merck, Bristol-Myers Squibb, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and Leo Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Cesar Francisco Pacheco Tena Consultant of: Eli Lilly, AbbVie, Roche, Pfizer, Janssen, Astra-Zeneca, UCB, Gilead, R-Pharm, Sanofi Regeneron, Grant/research support from: Eli Lilly, AbbVie, Roche, Pfizer, Janssen, Astra-Zeneca, UCB, Gilead, R-Pharm, Sanofi Regeneron, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Consultant of: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, UCB, Grant/research support from: AbbVie, Adiga Life-Sciences, Amgen, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB, Liang Chen Shareholder of: AbbVie, Employee of: AbbVie, Yuanyuan Duan Shareholder of: AbbVie, Employee of: AbbVie, Patrick Zueger Shareholder of: AbbVie, Employee of: AbbVie, Jianzhong Liu Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Aileen Pangan Shareholder of: AbbVie, Employee of: AbbVie, Frank Behrens Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche, Chugai, BMS, UCB Pharma, Grant/research support from: Pfizer, Janssen, Chugai, Celgene and Roche.

Background:In the FINCH 3 study, filgotinib (FIL)—a potent, selective, oral small molecule Janus kinase 1 inhibitor1—in combination with methotrexate (MTX), demonstrated significant improvements in the signs and symptoms of rheumatoid arthritis (RA) vs MTX alone in patients (pts) who were MTX-naïve.2For pts with RA, rapid control of pain and fatigue along with maintenance of physical function and health-related quality of life (HRQoL) are important outcomes of their care.3Thus, patient-reported outcomes (PROs) can provide physicians with evidence to guide treatment decisions beyond the guideline-recommended treatment targets of reducing immune inflammation to prevent joint damage, physical disability, and mortality.4Objectives:To evaluate the rate and magnitude of change in PROs assessing functional status, pain, HRQoL, and fatigue from FINCH 3.Methods:In the FINCH 3 study (NCT02886728), pts with active RA who were MTX-naïve received FIL 200 mg daily + MTX, FIL 100 mg + MTX, FIL 200 mg (+ placebo [PBO]), or MTX (+ PBO) for up to 52 weeks. PROs were recorded prospectively and included HAQ-DI (functional status) and VAS pain scale (day 1, week [W]2, W4, W8, W12, W16, W20, W24, W30, W36, W44, W52), SF-36 (HRQoL), and FACIT-Fatigue (day 1, W4, W12, W24, W36, W52). The least squares mean of the change from baseline (CFB) at each time point up to W52 and p values (each FIL arm vs MTX) were analysed using a mixed-effects model for repeated measures. For HAQ-DI, the proportion of pts who achieved the minimum clinically important difference (MCID; reduction ≥0.22) between each FIL arm and MTX was analysed using logistic regression analysis. P values for the comparisons of PROs were not adjusted for multiplicity, except for HAQ-DI CFB at W24 for FIL 200 mg + MTX and FIL 100 mg + MTX vs MTX.Results:Of the 1249 pts randomised and treated (FIL 200 mg + MTX, n = 416; FIL 100 mg + MTX, n = 207; FIL 200 mg, n = 210; MTX, n = 416), 1025 (82.1%) completed the study. Compared with MTX alone, a nominally significantly greater CFB in functional status and pain from W2 to W24 was observed in all FIL arms; the benefit was sustained from W30 to W52 (Fig 1). By W2, a nominally significantly greater proportion of pts achieved the HAQ-DI MCID or greater (≥0.22) in all FIL arms (FIL 200 mg + MTX: 61.9%, p <0.001; FIL 100 mg + MTX: 58.5%, p <0.001; FIL 200 mg: 53.9%, p = 0.004) compared with MTX (42.2%). By W8, ≥72% of pts in all FIL arms vs 63% of pts in the MTX arm achieved the HAQ-DI MCID; a numerically greater proportion of pts in FIL arms vs MTX achieved HAQ-DI MCID through W52. SF-36 physical component summary and FACIT-Fatigue scores were nominally significantly improved with FIL treatment vs MTX alone at various time points (Fig 2A, B). Improvements in SF-36 mental component summary scores were nominally significant for pts in all FIL arms vs MTX alone as early as W4, and the CFB reached at W12 for FIL arms was generally sustained up to W52 (Fig 2A).Conclusion:For pts with moderate to severe RA who were MTX-naïve, FIL—with or without concomitant MTX—led to more rapid and sustained improvements in functional status, pain, fatigue, and HRQoL, compared with MTX alone.References:[1]Van Rompaey, et al.J Immunol. 2013;131:3568–77.[2]Westhovens, et al.Arthritis Rheumatol. 2019;71 (suppl 10):1606–8.[3]Fautrel B, et al.Rheumatol Int.2018;38:935–47.[4]Smolen JS, et al.Ann Rheum Dis.2017;76:960–77.Disclosure of Interests:Rieke Alten Grant/research support from: Pfizer, Galapagos, Galapagos NV, Gilead, Gilead Sciences, Inc., Novartis, Consultant of: Pfizer, Speakers bureau: Pfizer, William Rigby Consultant of: Gilead Sciences, Inc., Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ken Hasegawa Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Thijs Hendrikx Shareholder of: Galapagos (share/warrant holder), Employee of: Galapagos, Tatsuya Atsumi Grant/research support from: Eli Lily Japan K.K., Alexion Pharmaceuticals, Inc., Bristol-Myers Squibb Co., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Consultant of: Gilead Sciences, Inc., Eli Lilly Japan K.K., UCB Japan Co. Ltd., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Speakers bureau: Eli Lilly Japan K.K., UCB Japan Co. Ltd., Bristol-Myers Squibb Co., AbbVie Inc., Eisai Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead

BackgroundTofacitinib, an oral Janus Kinase inhibitor, is indicated in the treatment of adult patients (pts) with active, moderate to severe rheumatoid arthritis (RA).ObjectivesThe objective of this work is to describe the tofacitinib’s safety profile in the DeFacTo study (French prospective observational study).MethodsThe safety profile of tofacitinib was assessed on the basis of interim data from a descriptive analysis of pts having taken at least one dose of tofacitinib in the context of the DeFacTo study.ResultsOf the 313 pts enrolled in the study, 301 had received tofacitinib and were included in the safety analysis. Of these, 276 fulfilled the eligibility criteria and included 219 who had ≥ 1 year follow-up and a mean exposure period of 368 ± 197.1 days. As of 15 March 2021, 122 patients are continuing to take tofacitinib therapy (76 missing prescription data). On inclusion, 77.9% of the 276 pts were females of mean (± SD) age 59.7 ± 11.7 years and a median disease duration of 9.1 years [Q1;Q3: 4.1; 19.2]. A history of cardiovascular disease was found in 12.5% of cases, (4.4% myocardial infraction, 5.5% stroke/transient ischemic attack, 1.5% heart failure and 1.5% peripheral arterial occlusive disease); 5.5% had a history of cancer, 17.5% a prior infection and 46% were smokers/former smokers. Tofacitinib was prescribed in combination with a csDMARD in 58.3% of pts and with corticosteroids in 54.3% of cases. At the cut-off date of 15 March 2021, of the 301 patients, adverse effects (AE) had been reported in 44.9% of cases of which 10.6% were considered serious (SAE). Infections were detected in 18.6% of pts (Table 1).Table 1.Real life safety data for tofacitinib according to ageN, (%)< 65 years (n=190)≥ 65 years (n=110)Total (n=301*)Adverse effect80 (42.1)55 (50.0)135 (44.9)Serious adverse effect16 (8.4)16 (14.5)32 (10.6)Infection33 (17.4)23 (20.9)56 (18.6)Severe infection3 (1.6)4 (3.6)7 (2.3)AE of interest (number of events) Infection Herpes zoster5510 Severe infection Herpes zoster101 Tuberculosis022 Cancer Small-cell carcinoma011 MACE Stroke101 Thromboembolic events Venous thrombosis011Death000*1 patient for whom age is unknown but is counted in the total.ConclusionThese purely descriptive interim results reveal a safety profile for tofacitinib in patients with RA, similar to that previously reported in clinical and observational studies. (1-2)References[1]Wollenhaupt et al. Arthritis Research & Therapy (2019) 21:89 https://doi.org/10.1186/s13075-019-1866-2[2]Kremer et al. ACR Open Rheumatology 2021. DOI 10.1002/acr2.11232AcknowledgementsTo all investigators involved in this study, and all patients included in this studyDisclosure of InterestsCécile Gaujoux-Viala Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Amgen; Boeringhe; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Andre BASCH Speakers bureau: Janssen, Novartis, Amgen, BMS, Abbvie, Lilly, Pfizer, MSD, UCB, Consultant of: Janssen, Novartis, Amgen, BMS, Abbvie, Lilly, Pfizer, MSD, UCB,, Slim Lassoued: None declared, Fabienne COURY-LUCAS Consultant of: AbbVie, Bristol-Myers Squibb, Janssen, Lilly, MSD, Novartis and Pfizer, Grant/research support from: AbbVie, Biogen, Roche Chugai, Pfizer, and UCB,, Meriem Kessouri Shareholder of: Pfizer, Employee of: Pfizer, Nadir Mammar Shareholder of: Pfizer, Employee of: Pfizer, Yves Brault Shareholder of: Pfizer, Employee of: Pfizer, Thierry Lequerre Consultant of: Abbvie, BMS, Boeringher, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche – Chugai, Sanofi, UCB,, Carine Salliot Consultant of: Biogen, Lilly, Novartis, Roche Chugai, Pfizer

BackgroundTofacitinib, an oral Janus Kinase inhibitor, is indicated for the treatment of adult patients with moderate to severe active rheumatoid arthritis (RA).ObjectivesTo describe the safety profile of Tofacitinib in a French prospective observational study DeFacTo.MethodsThe safety profile of tofacitinib was assessed using interim data from a descriptive analysis of patients who took at least one dose of tofacitinib in the DeFacTo study.ResultsAmong 314 patients enrolled in the study, 306 received tofacitinib and were included in the safety analysis, including 274 patients with a follow-up ≥ 18 months (POP2) on 03/15/22 date of analysis) with a median exposure duration of 538 [Q1; Q3: 381; 554] days. 113 patients (41.2%) were still on tofacitinib (39 discontinued, 122 missing data regarding prescription). At inclusion, 78.3% of the 306 pts were women with a mean (± standard deviation) age of 59.5 ± 11.5 years, median disease duration of 8.9 years [Q1; Q3: 4.1; 18.9]. There was a history of cardiovascular (CV) disease in 11.9% of cases (including 4.6% myocardial infarction (MI), 5.0% stroke/transient ischemic attack (TIA), 1.7% heart failure, and 1.7% peripheral arterial disease); 5.6% history of cancer, 16.8% history of infection, and 46.6% smoker/former smoker. Tofacitinib was prescribed in combination with a csDMARD in 61.1% of patients and corticosteroids in 56.2% of cases. The results showed that adverse events (AEs) were reported in 54.2% of the 306 patients, 14.4% were considered as serious. Infections were found in 22.2% of patients, no deaths were reported (Table 1).Table 1.Real-life and age-specific safety data for tofacitinibN, (%)< 65 ans (n=193)≥ 65 ans (n=111)Total (n=306*)Adverse events (AEs)104 (53.9)62 (55.9)166 (54.2)Serious adverse events21 (10.9)23 (20.7)44 (14.4)Infection41 (21.2)27 (24.3)68 (22.2)Herpes Zoster6 (3.1)6 (5.4)12 (3.9)Serious AEs of special interestSerious infection5 (2.6)4 (3.6)9 (2.9)Herpes zosterTuberculosis1 (0.5)0 (0.0)0 (0.0)2 (1.8)1 (0.3)2 (0.7)Cancer1 (0.5)1 (0.9)2 (0.7)CV eventⴕ1 (0.5)1 (0.9)2 (0.7)VTEⱡ0 (0.0)2 (1.8)2 (0.7)Death0 (0.0)0 (0.0)0 (0.0)*2 patients with missing age but counted in the total. ⴕ cardiovascular event (Evt): non-fatal MI and stroke + CV death. ⱡ VTE (venous thromboembolic disease): deep vein thrombosis + pulmonary embolism.ConclusionThese intermediate, descriptive results show a safety profile of tofacitinib in real-life RA similar to the one previously reported in clinical and observational studies.[1-2]References[1]Wollenhaupt et al. Arthritis Research & Therapy (2019) 21:89https://doi.org/10.1186/s13075-019-1866-2[2]Kremer et al. ACR Open Rheumatology 2021. DOI 10.1002/acr2.11232AcknowledgementsThis study was sponsored by Pfizer.Disclosure of InterestsCécile Gaujoux-Viala Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Andre BASCH Consultant of: Janssen, Novartis, Amgen, BMS, Abbvie, Lilly, Pfizer, MSD, UCB, Slim Lassoued: None declared, Fabienne COURY-LUCAS Consultant of: AbbVie, Bristol-Myers Squibb, Janssen, Lilly, MSD, Novartis and Pfizer, Grant/research support from: AbbVie, Biogen, Roche Chugai, Pfizer, and UCB, Meriem Kessouri Shareholder of: Pfizer, Employee of: Pfizer, Yves Brault Shareholder of: Pfizer, Employee of: Pfizer, Thierry Lequerre Consultant of: Abbvie, BMS, Boeringher, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche – Chugai, Sanofi, UCB, Carine Salliot Consultant of: Biogen, Lilly, Novartis, Roche Chugai, Pfizer.

The aim of the paper is to investigate and understand the application of the project life cycle concept in the pharmaceutical field, with all its specificities and limitations. The purpose of the paper is to contribute to the understanding of the application of the project life cycle concept in pharmacy. Under the influence of various factors (expiration of patent protection, increase in total health care costs, tightening of regulatory requirements) it is practically no longer possible to manage pharma business without project management. The idea is to identify pros and cons of the current way of managing projects in this area by studying the existing literature on a given topic. The results of the research suggest that traditional project management in this area should be supplemented with other perspectives -the management of a pharmaceutical project should be reconsidered from a strategic, operational, organizational and financial point of view, that is, a broader picture of the project should be obtained. The paper should contribute to the improvement of the pharmaceutical project management process, both in industry and in healthcare. Improving the application of the concept of project management in pharmacy would bring benefits to the business of pharmaceutical organizations, but also to human health as a whole.

BackgroundBimekizumab (BKZ), a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, met all primary/secondary endpoints at Week (Wk) 16 in patients (pts) with active non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axSpA (r-axSpA; i.e., ankylosing spondylitis), in the parallel phase 3 BE MOBILE 1 and 2 studies, respectively.[1,2]ObjectivesTo assess efficacy and safety of BKZ in these pts up to Wk 52.MethodsBE MOBILE 1 (NCT03928704) and 2 (NCT03928743) both involved a 16-wk placebo (PBO)-controlled and 36-wk maintenance period.[1,2]Pts were randomised to subcutaneous BKZ 160 mg Q4W (BKZ) or to PBO then BKZ from Wk 16 (PBO/BKZ).Results220/254 (86.6%) randomised pts with nr-axSpA and 298/332 (89.8%) with r-axSpA completed Wk 52. Efficacy was sustained to Wk 52 in both studies (Table 1). ASAS40 responses in BKZ-randomised pts increased from Wk 16 (nr-axSpA: 47.7%; r-axSpA: 44.8%; non-responder imputation [NRI]) to Wk 52 (60.9%; 58.4%; NRI) with high levels of efficacy across TNFi-naïve and TNFi-IR populations (Table 1). At Wk 52, ASDAS <2.1 was achieved by 61.6% and 57.1%, and ASDAS <1.3 by 25.2% and 23.4%, of BKZ-randomised pts with nr-axSpA and r-axSpA, respectively (Figure 1). Wk 16 reductions from baseline in objective signs of inflammation (MRI, hs-CRP), and improvements in function (BASFI) and ASQoL, were maintained through 52 wks. Efficacy at Wk 52 was similar in PBO/BKZ-treated and BKZ-randomised pts (Table 1).At Wk 52, 75.0% (183/244) of pts with nr-axSpA and 75.5% (249/330) of pts with r-axSpA had ≥1 treatment-emergent adverse event (TEAE) on BKZ; the most frequent (% pts) TEAEs by preferred term (MedDRA v19.0) were nasopharyngitis (nr-axSpa: 12.3%; r-axSpA 9.1%) and upper respiratory tract infection (9.4%; 6.4%); few COVID-19 infections were reported (7.0%; 2.1%). Incidence (pts/100 pt years) of serious TEAEs were low (4.4; 7.1); no major adverse cardiovascular events, active tuberculosis cases, serious COVID-19 infections, or deaths were reported. Most incidences of fungal infection (19.6; 14.9; none serious or systemic) wereCandida(12.8; 8.3) and mild to moderate; two pts in both studies discontinued the study due toCandidainfections. Incidence of IBD (1.0; 1.0) and uveitis (1.5; 2.4) were low.ConclusionAcross the axSpA spectrum, BKZ resulted in sustained efficacy to Wk 52. No new safety signals were observed, consistent with the Wk 24 safety profile.[1,2]References[1]Deodhar A. Ann Rheum Dis 2022;81:772–3; 2.[2]van der Heijde D. Ann Rheum Dis 2022;81:12–3.Table 1.Efficacy at Wk 52Mean (SE), unless statedBE MOBILE 1BE MOBILE 2PBO→BKZ N=126BKZ N=128PBO→BKZ N=111BKZ N=221ASAS40[NRI]n (%)64 (50.8)78 (60.9)76 (68.5)129 (58.4)ASAS40 in TNFi-naïve[NRI]n (%)58 (53.2)a73 (61.9)b67 (71.3)c108 (58.7)dASAS40 in TNFi-IRe[NRI]n (%)6 (35.3)f5 (50.0)g9 (52.9)f21 (56.8)hASAS20[NRI]n (%)88 (69.8)94 (73.4)89 (80.2)158 (71.5)ASAS PR[NRI]n (%)38 (30.2)38 (29.7)41 (36.9)66 (29.9)ASAS 5/6[NRI]n (%)65 (51.6)71 (55.5)74 (66.7)124 (56.1)BASDAI CfB[MI]–3.5 (0.2)–3.9 (0.2)–4.0 (0.2)–3.6 (0.1)BASFI CfB[MI]–2.6 (0.2)–3.0 (0.2)–2.8 (0.2)–2.8 (0.1)ASDAS-MI[NRI]n (%)37 (29.4)47 (36.7)49 (44.1)71 (32.1)Nocturnal spinal pain CfB[MI]–4.1 (0.2)–4.3 (0.3)–4.6 (0.3)–4.1 (0.2)ASQoL CfB[MI]–5.3 (0.4)–5.9 (0.4)–5.6 (0.4)–5.7 (0.3)SF-36 PCS CfB[MI]11.4 (0.9)12.2 (0.9)12.3 (0.9)12.0 (0.6)BASMI CfB[MI]–0.4 (0.1)–0.6 (0.1)–0.7 (0.1)–0.7 (0.1)Total resolution of enthesitisi[NRI]n (%)41 (44.6)j51 (54.3)c31 (46.3)k67 (50.8)lASDAS-CRP CfB[MI]–1.6 (0.1)–1.8 (0.1)–1.9 (0.1)–1.7 (0.1)SPARCC MRI SIJ score CfB[OC]mMean (SD)–6.4 (10.7)n–7.6 (10.5)o–2.8 (6.1)p–4.7 (8.2)qBerlin MRI spine score CfB[OC]mMean (SD)–0.4 (2.0)k–0.7 (2.5)r–2.1 (3.4)p–2.4 (3.9)shs-CRP, mg/L [MI]Median2.21.72.02.3RS. n:a109,b118,c94,d184;eMax 1 TNFi; n:f17,g10,h37;iMASES=0 in pts with MASES >0 at BL; n:j92,k67;l132;mMRI sub-study; n:n70,o82,p48,q90,r79,s89.AcknowledgementsThis study was funded by UCB Pharma. Medical writing support was provided by Costello Medical, funded by UCB Pharma.Disclosure of InterestsXenofon Baraliakos Speakers bureau: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Paid instructor for: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, BMS, Chugai, Eli Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer and UCB Pharma, Atul Deodhar Speakers bureau: Janssen, Novartis and Pfizer, Consultant of: AbbVie, Amgen, Aurinia, BMS, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie, BMS, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, GSK, Janssen, Eli Lilly, Novartis, Pfizer and UCB Pharma, Employee of: Director of Imaging Rheumatology BV, Marina Magrey Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and UCB Pharma, Walter P Maksymowych Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: AbbVie and Pfizer; educational grants from AbbVie, Janssen, Novartis and Pfizer, Employee of: Chief Medical Officer for CARE ARTHRITIS, Tetsuya Tomita Speakers bureau: AbbVie, Astellas, BMS, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Mitsubishi-Tanabe, Novartis and Pfizer, Consultant of: AbbVie, Eli Lilly, Gilead, Novartis and Pfizer, Huji Xu Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Beigene, BioMap, IASO, Pfizer and UCB Pharma, Employee of: Clinical investigator for Peking-Tsinghua Center for Life Sciences, Marga Oortgiesen Shareholder of: UCB Pharma, Employee of: UCB Pharma, Ute Massow Employee of: UCB Pharma, Carmen Fleurinck Employee of: UCB Pharma, Alicia Ellis Employee of: UCB Pharma, Thomas Vaux Employee of: UCB Pharma, julie smith Employee of: UCB Pharma, Alexander Marten Employee of: UCB Pharma, Lianne S. Gensler Consultant of: AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer and UCB Pharma, Grant/research support from: Novartis and UCB Pharma paid to institution.

Plenaries and Special Presentations:Supriya Sharma, Acting Associate Assistant Deputy Minister, Health Canada: "Facing Tomorrow's Regulatory Challenges Today"Mick Bhatia, McMaster Stem Cell and Cancer Research Institute (SCC-RI): "Potential Applications of Human Stem Cells in Therapeutics"You Han Bae, University of Utah: "Current Paradigm of Cancer Nanomedicine and its Perspective - A Gap Between Experimental & Clinical Worlds"Laszlo Endrenyi, University of Toronto: CSPS Lifetime Achievement Award - "Sense and Sensibility (?) in Science"Rav Kumar, GlaxoSmithKline: CSPS Award of Leadership in Canadian Pharmaceutical Sciences - "A Bright Future for Pharmaceutical Sciences in Canada"Emmanuel Ho, University of Manitoba: GlaxoSmithKline/CSPS Early Career Award - "Development of Intravaginal Microbicides for the Prevention of HIV Infection"Building Opportunity Day:- The Life Sciences Industry in Canada: Now and the Future…- Start-up Pharma: Case Studies- Supporting Industry: Funding PanelConference Sessions:1. Early Discovery2. Latest Topics in Bioequivalence3. Successful Candidate Selection from Druggability to Regulatory Submission4. Regulatory Considerations and Analysis of Subsequent Entry Biologics5. Nanomedicine 6. Going Beyond Oral Delivery … Strategies to Enable Drugs to Reach New Targets7. New Trends in Mass Spectrometry for Drug Discovery & Development8. Biomarkers in Pharmacotherapy and Drug Development9. Application of Quality by Design (QbD) and Lifecycle Management to Analytical Procedure10. Current Topics in Drug Safety 11. Recent Trends in Material and Biomaterial Research

Abstract Background The pathogenesis of inflammatory bowel disease (IBD) which includes Crohn’s disease (CD) and ulcerative colitis (UC), is believed to involve activation of the intestinal immune system in response to the gut microbiome among genetically susceptible hosts. IBD has been historically regarded as a disease of developed nations, though in the past two decades there has been a reported shift in the epidemiological pattern of disease. High-income nations with known high prevalence of disease are seeing a stabilization of incident cases, while a rapid rise of incident IBD is being observed in developing nations. This suggests that environmental exposures may play a role in mediating the risk of developing IBD. The potential environmental determinants of IBD across various regions is vast, though medications have been increasingly recognized as one broad category of risk factors. Purpose Several medications have been considered to contribute to the etiology of IBD. This study assessed the association between medication use and risk of developing IBD using the Prospective Urban Rural Epidemiology (PURE) cohort. Method This was a prospective cohort study of 133,137 individuals between the ages of 20-80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed prospectively at least every 3 years. The main outcome was development of IBD, including CD and UC. Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) was evaluated. Results are presented as adjusted odds ratios (aOR) with 95% confidence intervals (CI). Result(s) During the median follow-up of 11.0 years [interquartile range (IQR) 9.2-12.2], we recorded 571 incident cases of IBD (143 CD and 428 UC). Higher risk of incident IBD was associated with baseline antibiotic use [aOR: 2.81 (95% CI: 1.67-4.73), p=0.0001] and hormonal medication use [aOR: 4.43 (95% CI: 1.78-11.01), p=0.001]. Among females, previous or current oral contraceptive use was also associated with IBD development [aOR: 2.17 (95% CI: 1.70-2.77), p=5.02E-10]. NSAID users were also observed to have increased risk of IBD [aOR: 1.80 (95% CI: 1.23-2.64), p=0.002], which was driven by long-term users [aOR: 5.58 (95% CI: 2.26-13.80), p&lt;0.001]. All significant results were consistent in direction for CD and UC with low heterogeneity. Conclusion(s) Antibiotics, hormonal medications, oral contraceptives, and long-term NSAID use were associated with increased odds of incident IBD after adjustment for covariates. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding below: Salim Yusuf is supported by the Heart & Stroke Foundation/Marion W. Burke Chair in Cardiovascular Disease. The PURE Study is an investigator-initiated study funded by the Population Health Research Institute, the Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Ontario, support from CIHR’s Strategy for Patient Oriented Research (SPOR) through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care and through unrestricted grants from several pharmaceutical companies, with major contributions from AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, and GlaxoSmithkline, and additional contributions from Novartis and King Pharma and from various national or local organisations in participating countries; these include: Argentina: Fundacion ECLA; Bangladesh: Independent University, Bangladesh and Mitra and Associates; Brazil: Unilever Health Institute, Brazil; Canada: Public Health Agency of Canada and Champlain Cardiovascular Disease Prevention Network; Chile: Universidad de la Frontera; China: National Center for Cardiovascular Diseases; Colombia: Colciencias, grant number 6566-04-18062; India: Indian Council of Medical Research; Malaysia: Ministry of Science, Technology and Innovation of Malaysia, grant numbers 100 -IRDC/BIOTEK 16/6/21 (13/2007) and 07-05-IFN-BPH 010, Ministry of Higher Education of Malaysia grant number 600 -RMI/LRGS/5/3 (2/2011), Universiti Teknologi MARA, Universiti Kebangsaan Malaysia (UKM-Hejim-Komuniti-15-2010); occupied Palestinian territory: the UN Relief and Works Agency for Palestine Refugees in the Near East, occupied Palestinian territory; International Development Research Centre, Canada; Philippines: Philippine Council for Health Research & Development; Poland: Polish Ministry of Science and Higher Education grant number 290/W-PURE/2008/0, Wroclaw Medical University; Saudi Arabia: the Deanship of Scientific Research at King Saud University, Riyadh, Saudi Arabia (research group number RG -1436-013); South Africa: the North-West University, SANPAD (SA and Netherlands Programme for Alternative Development), National Research Foundation, Medical Research Council of SA, The SA Sugar Association (SASA), Faculty of Community and Health Sciences (UWC); Sweden: grants from the Swedish state under the Agreement concerning research and education of doctors; the Swedish Heart and Lung Foundation; the Swedish Research Council; the Swedish Council for Health, Working Life and Welfare, King Gustaf V’s and Queen Victoria Freemasons Foundation, AFA Insurance, Swedish Council for Working Life and Social Research, Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning, grant from the Swedish State under the Läkar Utbildnings Avtalet agreement, and grant from the Västra Götaland Region; Turkey: Metabolic Syndrome Society, AstraZeneca, Turkey, Sanofi Aventis, Turkey; United Arab Emirates (UAE): Sheikh Hamdan Bin Rashid Al Maktoum Award For Medical Sciences and Dubai Health Authority, Dubai UAE. Disclosure of Interest C. Pray: None Declared, N. Narula Grant / Research support from: Neeraj Narula holds a McMaster University Department of Medicine Internal Career Award. Neeraj Narula has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, and Ferring, E. C. Wong: None Declared, J. K. Marshall Grant / Research support from: John K. Marshall has received honoraria from Janssen, AbbVie, Allergan, Bristol-Meyer-Squibb, Ferring, Janssen, Lilly, Lupin, Merck, Pfizer, Pharmascience, Roche, Shire, Takeda and Teva., S. Rangarajan: None Declared, S. Islam: None Declared, A. Bahonar: None Declared, K. F. Alhabib: None Declared, A. Kontsevaya: None Declared, F. Ariffin: None Declared, H. U. Co: None Declared, W. Al Sharief: None Declared, A. Szuba: None Declared, A. Wielgosz: None Declared, M. L. Diaz: None Declared, R. Yusuf: None Declared, L. Kruger: None Declared, B. Soman: None Declared, Y. Li: None Declared, C. Wang: None Declared, L. Yin: None Declared, M. Erkin: None Declared, F. Lanas: None Declared, K. Davletov: None Declared, A. Rosengren: None Declared, P. Lopez-Jaramillo: None Declared, R. Khatib: None Declared, A. Oguz: None Declared, R. Iqbal: None Declared, K. Yeates: None Declared, Á. Avezum: None Declared, W. Reinisch Consultant of: Speaker for Abbott Laboratories, Abbvie, Aesca, Aptalis, Astellas, Centocor, Celltrion, Danone Austria, Elan, Falk Pharma GmbH, Ferring, Immundiagnostik, Mitsubishi Tanabe Pharma Corporation, MSD, Otsuka, PDL, Pharmacosmos, PLS Education, Schering-Plough, Shire, Takeda, Therakos, Vifor, Yakult, Consultant for Abbott Laboratories, Abbvie, Aesca, Algernon, Amgen, AM Pharma, AMT, AOP Orphan, Arena Pharmaceuticals, Astellas, Astra Zeneca, Avaxia, Roland Berger GmBH, Bioclinica, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Covance, Danone Austria, DSM, Elan, Eli Lilly, Ernest & Young, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, LivaNova, Mallinckrodt, Medahead, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nash Pharmaceuticals, Nestle, Nippon Kayaku, Novartis, Ocera, Omass, Otsuka, Parexel, PDL, Periconsulting, Pharmacosmos, Philip Morris Institute, Pfizer, Procter & Gamble, Prometheus, Protagonist, Provention, Robarts Clinical Trial, Sandoz, Schering-Plough, Second Genome, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Therakos, Theravance, Tigenix, UCB, Vifor, Zealand, Zyngenia, and 4SC, Advisory board member for Abbott Laboratories, Abbvie, Aesca, Amgen, AM Pharma, Astellas, Astra Zeneca, Avaxia, Biogen IDEC, Boehringer-Ingelheim, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Celltrion, Danone Austria, DSM, Elan, Ferring, Galapagos, Genentech, Grünenthal, Inova, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millenium, Mitsubishi Tanabe Pharma Corporation, MSD, Nestle, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble, Prometheus, Sandoz, Schering-Plough, Second Genome, Setpointmedical, Takeda, Therakos, Tigenix, UCB, Zealand, Zyngenia, and 4SC, P. Moayyedi: None Declared, S. Yusuf: None Declared

Background:Bimekizumab (BKZ), a monoclonal antibody that selectively neutralises interleukin (IL)-17A and IL-17F, is a potential therapeutic option in ankylosing spondylitis (AS).Objectives:To report 48-week (wk) patient-reported outcomes (PROs) in patients (pts) with AS treated with BKZ in a phase 2b dose-ranging study (BE-AGILE;NCT02963506).Methods:Pts with active AS (Bath AS Disease Activity Index [BASDAI] ≥4; spinal pain ≥4 [0–10]), fulfilling modified New York criteria (central reading), and inadequate response/intolerance to NSAIDs were randomised according to the study design (Figure 1). PROs included spinal pain, fatigue (BASDAI Q1), morning stiffness (mean of BASDAI Q5 + 6), Bath AS Functional Index (BASFI), Medical Outcomes Study (MOS) Sleep Problems Index II and AS Quality of Life questionnaire (ASQoL). Efficacy is reported for pts initially randomised to placebo (PBO) or BKZ 160/320 mg every 4 weeks (Q4W); treatment-emergent adverse events (TEAEs) are reported for pts who received ≥1 dose of study drug (Safety Set).Results:Of 303 pts, 181 were randomised to PBO or BKZ 160/320 Q4W mg at Wk 0; 179/181 completed Wk 12 and 161/181 completed Wk 48. At Wk 12, improvements in pain, fatigue, morning stiffness, BASFI, sleep and ASQoL were greater in BKZ pts vs PBO pts. Responses were further improved or maintained to Wk 48, with no meaningful differences between BKZ 160 mg and 320 mg (Table 1). Serious TEAEs occurred in 13/303 (4.3%) pts (Table 2), which included 2 major adverse cardiac events considered not related to study drug. Oral candidiasis occurred in 16 (5.3%) pts.Table 1.PRO efficacy endpoints to Week 48 (multiple imputation)Mean (SD)WkPBO – BKZ 160 mg(n=24)PBO – BKZ 320 mg(n=36)BKZ 160 mg(n=58)BKZ 320 mg(n=61)Spinal pain06.9 (1.4)7.0 (1.9)6.6 (2.0)7.3 (1.5)CfB12-1.5 (1.6)-0.7 (1.7)-2.6 (2.2)-3.6 (2.4)48-3.7 (2.0)-3.7 (2.6)-3.8 (2.4)-4.7 (2.1)Fatigue06.4 (1.7)6.8 (1.6)6.4 (1.7)6.4 (1.9)CfB12-0.7 (2.5)-1.0 (1.7)-2.1 (2.2)-2.1 (2.5)48-2.7 (2.2)-2.8 (2.4)-3.1 (2.1)-3.3 (2.4)Morning stiffness06.9 (1.7)6.7 (2.0)6.5 (1.8)6.6 (2.1)CfB12-1.5 (1.7)-1.1 (1.5)-2.8 (2.0)-3.4 (2.7)48-3.9 (2.2)-3.6 (2.4)-3.9 (2.2)-4.4 (2.4)BASFI05.8 (1.8)5.5 (2.2)5.5 (2.2)5.9 (2.0)CfB12-1.0 (2.1)-0.3 (1.7)-1.7 (1.8)-2.2 (2.0)48-2.9 (2.2)-2.4 (2.2)-2.5 (2.0)-2.9 (2.2)MOS Sleep Problems Index II045.5 (8.1)45.3 (7.9)46.9 (7.5)47.2 (9.4)CfB122.1 (8.3)1.8 (6.8)5.6 (6.7)6.8 (7.5)487.6 (8.7)8.0 (9.1)6.5 (6.1)8.0 (7.9)ASQoL08.4 (4.7)9.2 (4.7)8.4 (4.3)8.7 (4.3)CfB12-1.3 (5.5)-1.3 (3.7)-3.5 (4.3)-4.6 (4.8)48-4.2 (5.6)-5.3 (5.6)-4.9 (4.1)-5.4 (4.8)CfB: change from baselineTable 2.Overview of TEAEs to Week 48 (Safety Set; N=303)n (%)BKZ 160 mg(n=149)BKZ 320 mg(n=150)All BKZ [a](N=303)Any TEAE103 (69.1)122 (81.3)235 (77.6)Drug-related TEAEs48 (32.2)54 (36.0)110 (36.3)Serious TEAEs5 (3.4)6 (4.0)13 (4.3)Discontinuations due to TEAEs7 (4.7)10 (6.7)20 (6.6)[a] Includes TEAEs for 16 and 64 mg BKZConclusion:Pts with active AS demonstrated rapid and sustained improvements in PROs, sleep and quality of life over 48 wks of BKZ treatment. BKZ was generally well tolerated with no unexpected safety findings versus previous studies.Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Lianne S. Gensler Grant/research support from: Pfizer, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, GSK, Novartis, UCB, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Alan Kivitz Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi, Mary Katherine Farmer Employee of: UCB Pharma, Dominique Baeten Employee of: UCB Pharma, Nadine Goldammer Employee of: UCB Pharma, Jason Coarse Employee of: UCB Pharma, Marga Oortgiesen Employee of: UCB Pharma, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma

The journalistic stereotypes of BGI (the world’s largest sequencing centre) as a Chinese state venture, and of Singapore’s Genome Institute of Science (GIS) as a neoliberal platform, are inverted. Methodologically, by looking at qualitative networks, charismatic leaders and research strategies, this essay proposes a finer grained, meso-level, ethnographic analysis that allows for multi-scalar tracking and juxtaposition as generators of comparative insights. It deploys a social hieroglyphic analysis of the leaders of BGI and an updated account of the post-2010 ‘industrial re-alignment’ of GIS to highlight the role of cross-national networks in the construction of what are usually seen as national science projects, as well as the roles of mixed state and market strategies, and mixed clinical, basic science, biotech and big pharma protocols and platforms of the contemporary life sciences. It pays particular attention to the small worlds of the scientific republic and the charismatic voices of leaders forging new institutional arrangements.

BackgroundTocilizumab (TCZ) was approved for systemic juvenile idiopathic arthritis (sJIA) as an intravenous formulation in 2008 after its effectiveness and safety were shown in a world-leading clinical trial performed in Japan in 2002–2008.ObjectivesThis study aimed to understand the long-term prognosis of patients participating in phases II (Study MRA011JP), III (Study MRA316JP), and III/IV (Study MRA324JP). There were 149 participants in the clinical trial.MethodsInformation on eligible patients was obtained from 12 cooperating institutions approved by the Ethics Committee of Tokyo Women’s Medical University and each institution. Patients who could be followed-up were referred and transferred to other hospitals or departments. The following long-term prognoses were assessed: treatment status, including the continuation of TCZ administration during the long-term course of sJIA, disease status (remission rate and clinical phenotype), complications, social adjustment, employment status, andhealth-relatedquality of life (HRQOL) scale.ResultsResults were collected for 132 cases from ten centers by December 2022. We examined 125 patients (58 males and 67 females) whose medical records were still available and whose final diagnosis was sJIA. The age of the study participants was 18.6 years at the time of the study, 4.3 years at onset, 8.8 years at first TCZ administration, 3.8 years from onset to the first TCZ administration, and 9.1 years from TCZ initiation (all median values). Of the 125 patients, 28 (22.4%) were in medication-free remission and were either under or completely followed-up. Of the 93 patients (74.4%) who continued therapy, 10 (10.8%) were moved to a subcutaneous version of TCZ, which is not yet licensed for the treatment of sJIA in Japan. Ten patients (10.8%) were switched to canakinumab (CAN) due to TCZ primary failure (5 patients), secondary failure (2 patients), side effects (1 patient developed anaphylaxis), or other reasons. Of the 124 patients, 44 (35.5%) changed from acute febrile sJIA to chronic arthritic sJIA, in which chronic arthritis was the primary pathology without systemic inflammation, and 17 of these patients still had active arthritis at the last observation. Corticosteroids were prescribed in 54 of 93 patients (58.1%). Except in one case of sudden death, the causes of death in the four cases that resulted in fatalities were macrophage activation syndrome, sJIA-related interstitial pneumonia, and disseminated aspergillosis. The most commonly observed complications were osteoporosis in 68 (54.4%), infection requiring hospitalization in 32 (25.6%), and hypertension in 25 (20%). The EQ-5D-5L score was 0.91 (mean). The final mean height of the patients whose information was available after the age of 18 years (n = 62) was 157.7 cm for males (mean 170.4 cm in Japanese) and 144.3 cm for females (mean 156.7 cm in Japanese), showing a significant short stature. The college/university enrollment rate was as high as 68.4% (Japanese statistical data: 58.9%), and all but five students were employed.ConclusionSeventy-four percent of the patients continued treatment with TCZ or CAN, and conversion to chronic arthritic sJIA was observed in 35.5%. Despite issues such as growth retardation, social adjustment and employment status were promising, suggesting a contribution of treatment.Reference[1]Yokota S, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomized, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008 Mar 22;371(9617):998-1006.Acknowledgements:NIL.Disclosure of InterestsTakako Miyamae Speakers bureau: TM has received speaker’s fee from AbbVie Japan GK, Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Novartis Japan, Pfizer Japan Inc. , Tomohiro Kawabe: None declared, Kenichi Nishimura Speakers bureau: Novaritis Pharma, Grant/research support from: Chugai Pharma, Seira Hattori Grant/research support from: Chugai Pharma, Tomoyuki Imagawa: None declared, Tomonori Ishii Speakers bureau: Paid as speaker, chugai, Shuichi Ito Paid instructor for: Novaritis Pharma, Chugai Pharma, Grant/research support from: Chugai Pharma, Naomi Iwata: None declared, Yasuyuki Kamata: None declared, Yuji Kamiyama Grant/research support from: Chugai Pharma, Mao Mizuta Speakers bureau: Novartis Pharma K.K., Masaaki Mori Speakers bureau: I have received lecture fees from MSD, Chugai, UCB Japan, Abbvie Japan, Japan Blood Products Organization, AYUMI, and Asahi-Kasei., Grant/research support from: I belong to the department that is financially supported by Chugai, UCB Japan, CSL Behring, Abbvie Japan, Japan Blood Products Organization, AYUMI, Nippon Kayaku, and Asahi-Kasei., Ayako Murase Grant/research support from: Chugai Pharma, Yasuo Nakagishi Speakers bureau: CHUGAI PHARMACEUTICAL CO.,LTD. Novartis Pharma K.K. AstraZeneca plc, Taiji Nakano Grant/research support from: Maruho Co., Ltd 500,000 yen, Torii Pharmaceutical Co., Ltd 300,000 yen, Shingo Nakayamada Speakers bureau: S Nakayamada has received consulting fees, lecture fees, and/or honoraria from Bristol-Myers, AstraZeneca, Pfizer, GlaxoSmithKline, AbbVie, Astellas, Asahi-kasei, Sanofi, Chugai, Eisai, Gilead Sciences, Boehringer Ingelheim., Grant/research support from: S. Nakayamada has received research grants from Mitsubishi-Tanabe, Tomo Nozawa Grant/research support from: Chugai Pharma, Takashi Ohya Grant/research support from: Chugai Pharma, Nami Okamoto Speakers bureau: N.O. has received honoraria or lecture fees from AbbVie Inc.; Amgen Inc.; Asahi Kasei Pharma Corporation; Astellas Pharma Inc.; AstraZeneca PLC; AYUMI Pharmaceutical Co., Ltd.; Bristol Myers Squibb; Chugai Pharmaceutical Co., Ltd.; Eisai Co., Ltd.; Eli Lilly Japan K.K.; GlaxoSmithKline PLC; Mitsubishi Tanabe Pharma Corporation; Novartis Pharma K.K.; Pfizer Inc.; and Teijin Pharma Limited;., Paid instructor for: N.O. has has received consulting fees from Daiichi Sankyo Company Limited; Eli Lilly Japan K.K.; and Swedish Orphan Biovitrum AB, Kojiro Sato Speakers bureau: Chugai Pharmaceutical Co., Ltd, One time, 100,000 yen, Grant/research support from: Chugai Pharmaceutical Co., Ltd, Four times, average 1,800,000 yen, Yuko Sugita: None declared, Shuji Takei Speakers bureau: Glaxo Smith Klein Pharmaceuticals Ltd, Novartis Pharma K.K., AbbVie, Mitsubishi Tanabe Pharma Corporation, Ayumimi Pharmaceutical Co, Bristol-Myers Squibb, Eli-Lilly,K.K., Asahi Kasei Medical Co., Sanofi, K.K., Grant/research support from: Chugai Pharcaceutical Co.Ltd., Eisai Co.Ltd., Yoshiya Tanaka Speakers bureau: Y. Tanaka has received speaking fees and/or honoraria from Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Y. Tanaka has received research grants from Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim., Minako Tomiita: None declared, Hiroaki Umebayashi Speakers bureau: Novartis, Yuichi Yamasaki: None declared, Norihiro Nishimoto Speakers bureau: I have been paid as a speaker for Chugai Pharmaceutical Co. Ltd.,the product company of tocilizumab., Paid instructor for: I have been a paid instructor for Chugai Pharmaceutical Co. Ltd.,the product company of tocilizumab., Consultant of: I have been work as a paid consultant for Chugai Pharmaceutical Co. Ltd.,the product company of tocilizumab., Grant/research support from: I have received financial grants from Chugai Pharmaceutical Co. Ltd.,the product company of tocilizumab., Shumpei Yokota: None declared.

BackgroundDeucravacitinib (DEUC) is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action distinct from Janus kinase (JAK) 1/2/3 inhibitors. DEUC mediates signalling of key cytokines in psoriatic arthritis (PsA) and psoriasis (PsO). DEUC was well tolerated and efficacious vs placebo (PBO) in a Phase 2 trial in patients (pts) with PsA,1 and vs PBO or apremilast in 2 Phase 3 PsO trials.2ObjectivesTo assess the effects of DEUC on multiple laboratory parameters through the first 16 weeks of treatment (PBO-controlled) in these trials.MethodsThe Phase 2 double-blind PsA trial randomised pts (n=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or 12 mg QD. The Phase 3 double-blind PsO trials, POETYK PSO-1 and POETYK PSO-2, randomised pts (n=666 and 1020, respectively) 1:2:1 to PBO, DEUC 6 mg QD, or apremilast 30 mg twice daily. Changes from baseline in haematologic (neutrophils, lymphocytes, platelets, haemoglobin) and chemistry (cholesterol, triglycerides, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and creatine phosphokinase [CPK]) parameters were evaluated. Shifts in Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) severity grade ≥3 of laboratory abnormalities were assessed.ResultsIn the PsA trial, 65% of pts were on concomitant conventional synthetic DMARDs (csDMARDs) and 54.7% of pts were on methotrexate. The vast majority of pts continued to have laboratory parameters within normal range throughout the 3 trials in PsO and PsA. No clinically meaningful changes from baseline were observed in laboratory parameters in pts treated with DEUC, PBO, or apremilast. Rates of CTCAE grade 3 and 4 were rare (≤1 pt) and similar across DEUC-, PBO-, and apremilast-treated pts for the following parameters: lymphocytes, neutrophils, platelets, haemoglobin, AST, ALT, and cholesterol (Table 1). Shifts to CTCAE grades ≥3 in triglycerides and CPK were infrequent and generally comparable across treatment arms.Table 1.Maximal shifts to Grades ≥3 in laboratory parameters, Weeks 0-16PsA Phase 2PsO Phase 3aCTCAE TermGradePlacebo (n=66)n (%)DEUC 6 mg QD (n=70)n (%)DEUC 12 mg QD (n=67)n (%)Placebo (n=419)n (%)DEUC 6 mg QD (n=842)n (%)Apremilast 30 mg BID (n=422)n (%)BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16Lymphocyte count decreased340000001 (1.4)00000001 (0.2)0001 (0.1)00000Neutrophil count decreased34000000000000001 (0.2)01 (0.1) 01 (0.1)00000Platelet count decreased34000000000000000000000000Anaemia340N/A0N/A0N/A0N/A0N/A0 N/A0N/A0N/A0N/A0 N/A0N/A1 (0.2) N/AAlanine aminotransferase increased34000 000000 0000 0000000000 0Aspartate aminotransferase increased34000000000 01 (1.6)0000 00 01 (0.1)0001 (0.2) 0CPK increased34001 (1.5) 0000 00001 (1.6)1 (0.2) 03 (0.7) 1 (0.2)1 (0.1) 05 (0.6) 6 (0.7)1 (0.2)02 (0.5) 1 (0.2)Cholesterol high3400000000000 00 00 00 00 00000Hypertriglyceridemia34000 01 (1.4) 1 (1.4)2 (2.9) 1 (1.4)1 (1.6) 04 (6.0) 02 (0.5) 1 (0.2)6 (1.5) 04 (0.5)1 (0.1)12 (1.5)2 (0.2)3 (0.7) 08 (2.0) 0aPOETYK PSO-1 and PSO-2 pooled data.BID, twice daily; BL, baseline; CPK, creatine phosphokinase; CTCAE, Common Terminology Criteria for Adverse Events; DEUC, deucravacitinib; N/A, not applicable because there is no haemoglobin value for CTCAE Grade 4 (life-threatening consequences; urgent intervention indicated); PsA, psoriatic arthritis; PsO, psoriasis; QD, once daily; Wk, week.ConclusionDEUC treatment did not result in clinically meaningful laboratory changes, abnormalities often seen with JAK 1/2/3 inhibition, through 16 weeks of treatment in a Phase 2 trial in PsA, despite two-thirds of pts being on concomitant csDMARDs, and in 2 large Phase 3 trials in PsO.References[1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press).[2]Armstrong A et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb.Disclosure of InterestsRoy M. Fleischmann Consultant of: Abbvie, Acea, Akros, Amgen, Bristol Myers Squibb, Celtrion, Eli Lilly & Co., Galvani, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi Aventis, Taiho, and UCB., Grant/research support from: AbbVie, Acea, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly & Co., Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Pfizer, Roche/Genentech, Samumed, Sanofi Aventis, and UCB, Diamant Thaçi Consultant of: Advisory board, principal investigator, and lecture fees: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS-Pharma, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche-Posay, Samsung, Sandoz-Hexal, Sanofi, and UCB., Melinda Gooderham Consultant of: Investigator, speaker, advisory board member or consultant for: AbbVie, Akros, Amgen, Anaptys Bio, Arcutis, Aslan, Bausch, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, SUN Pharma, and UCB., Bruce Strober Consultant of: Honoraria or consultation fees: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol Myers Squibb, Connect Biopharma, Dermavant, Equillium, Janssen, Leo Pharma, Eli Lilly, Maruho, Meiji Seika Pharma, Mindera, Novartis, Pfizer, GlaxoSmithKline, UCB Pharma, Sun Pharma, Ortho Dermatologics, Regeneron, Sanofi-Genzyme, and Ventyxbio; Speaker: AbbVie, Janssen, Lilly, and Sanofi-Genzyme; Scientific co-director (consulting fee): CorEvitas Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Eli Lilly/Dermira, and Novartis., Neil J Korman Consultant of: Advisory board, consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi-Genzyme, Sun Pharma, and UCB, Grant/research support from: Grant support/principal investigator: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and Xbiotech. Speaker: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi-Genzyme., Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Lehman Shareholder of: Employees and shareholders of Bristol Myers Squibb, Employee of: Employees and shareholders of Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Antoine Sreih Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Akimichi Morita Consultant of: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Grant/research support from: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Philip J Mease Consultant of: Consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB., Grant/research support from: Research grants: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB;

Background: Central nervous system (CNS) involvement by peripheral T cell lymphoma (PTCL) is a rare condition. Among primary CNS lymphomas, only 2% are secondary to PTCL, while the risk of CNS relapse in all cases of PTCL is estimated at 2% to 6%. Little is known about the presentation and outcomes of PTCL patients with CNS involvement given the rarity of this entity. In this study, we describe patient characteristics, histology, and clinical course of patients with CNS involvement by PTCL. Methods: The Mayo Clinic Lymphoma Database was used to identify PTCL patients with primary or secondary CNS involvement seen at our institution between 2000 and 2018. A total of 12 patients were identified and their medical records were reviewed for patient and disease characteristics, CNS-directed treatment modality, and outcomes. The Kaplan-Meier method was used for time-to-event analysis. Results: The median age at CNS diagnosis was 63 years (range 41 to 76) and 11 (93%) patients were male. The histological diagnoses were PTCL, NOS in 9 (75%) patients, enteropathy-associated T-cell lymphoma in 2 (17%) patients, and angioimmunoblastic T-cell lymphoma in 1 (8%) patient. Five patients presented with primary T-cell CNS lymphoma (all with a PTCL, NOS histology), while the remaining 7 (58%) patients also had systemic involvement. All patients presented with neurologic symptoms at the time of CNS involvement diagnosis including: focal motor deficits in 6 patients (unilateral upper extremity weakness, gait impairments, and hemiparesis), cognitive decline in 5 patients (memory impairments, reduced attention, and confusion), headache in 4 patients, and seizure in 3 patients. The CNS disease location included the brain parenchyma in 9 (75%) patients, leptomeninges in 1 (8%) patient, and lumbar plexus in 1 (8%) patient. One patient (8%) had positive CSF finding only without radiologic evidence of involvement. CSF analysis was performed in 11 patients. Elevated protein levels were noted in 3 (27%) patients, malignant cells in 2 (18%), and no clear abnormalities in the remaining 6 (55%) patients. Concomitant bone marrow involvement was seen in only 1 patient. Elevated LDH was seen in 2 patients. The a median LDH was 195 U/L (range 139 to 4,360) The most common CNS-directed therapies were: high-dose methotrexate (MTX)-based regimens in 8 (67%) patients, including high-dose MTX in combination with temozolomide (n=2), or cytarabine and thiotepa (n=2). Intrathecal MTX, temozolomide and dexamethasone, lenalidomide, high-dose steroids, and surgical resection were the treatment modality used for one patient each. At a median follow up of 18 months, eight (75%) out of 12 patients were not alive at the time of last follow up. The median overall survival (OS) from diagnosis was 16 months (95% CI: 2.8-173). The median progression free survival (PFS) from initiation of CNS-directed therapy was 9 months (95% CI: 1.6-33) (figure). Four patients had a PFS longer than 12 months. These 4 patients were treated with: temozolomide/dexamethasone, high-dose MTX, lenalidomide, and high-dose MTX followed by cytarabine/thiothepa. Conclusion: CNS involvement by T-cell lymphoma is a rare complication that carries a poor prognosis. Early onset of neurologic symptoms should trigger prompt investigation of CNS involvement. Despite the short OS and PFS, some patients may achieve a relatively longer disease free interval. Disclosures Bennani: Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board. Cerhan:Celgene: Research Funding; NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Nowakowski:Celgene: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Curis: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Genentech, Inc.: Research Funding; MorphoSys: Consultancy, Research Funding; NanoString: Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees. Ansell:Mayo Clinic Rochester: Employment; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding. Paludo:Celgene: Research Funding; Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding.

BackgroundTofacitinib, an oral Janus Kinase inhibitor, is indicated in the treatment of adult patients (pts) with active, moderate to severe rheumatoid arthritis (RA). At the present time we have no data concerning its efficacy in a French RA population in a real-life setting.ObjectivesDeFacTo, is an on-going observational study the principal goal of which is to identify factors predictive of Tofacitinib drug survival in RA patients in real life.MethodsThese are the results of interim descriptive analyses of effectiveness data after 1 year of follow up.ResultsOf the 313 pts enrolled in the study, 276 pts were included in the effectiveness analysis (POP1), 219 of whom were patients with a ≥1-year follow-up (POP2) including 122 patients who, as of 15 March 2021, were continuing to take Tofacitinib therapy. At inclusion, POP1 (n=276) was composed of 77.9% females of mean (± SD) age 59.7 ± 11.7 years, having a median disease duration of 9.1 years [Q1;Q3: 4.1; 19.2], TJC 7.5 ± 5.9 and SJC 5.3 ± 5.1; 115 patients presented with erosions, 206 had RF+ and 202 had ACPA+. The median CRP value was 7.4 [: 3.0; 20.0] mg/l, DAS28-4-CRP was 4.6 ±1.1, and the FACIT-Fatigue score was 28.3 ± 11.3. In all, 96.7% of the pts had received prior treatment with ≥1 csDMARDs, 65.2% with b/tsDMARDs (median = 2 [1; 4]). Tofacitinib was prescribed in combination with a csDMARD in 58.3% of cases. The baseline characteristics of the 122 patients still taking tofacitinib at 12 months were comparable to those of POP1. Results showed continued treatment with tofacitinib in 85.3% of pts with mean duration of treatment of 368 ± 197.1 days and reductions from baseline in the parameters of inflammatory markers, pain and the DAS28 activity scores; 20% of 122 pts were in DAS28-CRP remission (Table 1). Safety findings were similar to those reported previously in clinical studies1 2.Table 1.Baseline characteristics and effectiveness at 12 months Patient characteristicsVariables: mean ± SD or % ptsInclusion, n=219At 12 months, n=122*PtGA (VAS, mm)60.6 ± 20.829.8 ± 22.8Pain (VAS, mm)57.3 ± 24.830.1 ± 25.7CRP (mg/l)15.5 ± 21.97.9 ± 13.3DAS28-4-CRP4.6 ± 1.02.8 ± 1.1DAS28-4-ESR4.9 ± 1.13.3 ± 1.2EffectivenessInclusion. n=219At 12 months. n=219 ⱡLDA, % pts- DAS28-CRP ≤3.26.828.8- DAS28-ESR ≤3.24.621.5Remission, % pts- DAS28-CRP <2.63.720.1- DAS28-ESR <2.62.79.6ConclusionThese real-life interim results for Tofacitinib in RA patients provide information on its use in France: with prescriptions for single drug therapy in 41.7% of cases, the effectiveness of Tofacitinib is confirmed as comparable to that found in clinical studies1-3.References[1]Burmester G et al. Lancet. 2013;381:451-460[2]Fleischman R et al. Lancet 2017;390:457-68[3]Wollenhaupt et al. Arthritis Research & Therapy (2019) 21:89 https://doi.org/10.1186/s13075-019-1866-2AcknowledgementsTo all investigators involved in this study, and all patients included in this studyDisclosure of InterestsCécile Gaujoux-Viala Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Amgen; Boeringhe; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Andre BASCH Speakers bureau: Janssen, Novartis, Amgen, BMS, Abbvie, Lilly, Pfizer, MSD, UCB, Consultant of: Janssen, Novartis, Amgen, BMS, Abbvie, Lilly, Pfizer, MSD, UCB,, Slim Lassoued: None declared, Fabienne COURY-LUCAS Consultant of: AbbVie, Bristol-Myers Squibb, Janssen, Lilly, MSD, Novartis and Pfizer, Grant/research support from: AbbVie, Biogen, Roche Chugai, Pfizer, and UCB,, Meriem Kessouri Shareholder of: Pfizer, Employee of: Pfizer, Nadir Mammar Shareholder of: Pfizer, Employee of: Pfizer, Yves Brault Employee of: Pfizer, Thierry Lequerre Consultant of: Abbvie, BMS, Boeringher, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche – Chugai, Sanofi, UCB,, Carine Salliot Consultant of: Biogen, Lilly, Novartis, Roche Chugai, Pfizer

Background:Gastro-intestinal tract (GIT) symptoms is highly prevalent in patients with systemic sclerosis (SSc). The GIT-symptoms impact on the quality of life is significant, and available treatment alternatives are limited. Recently published articles show associations between gut microbiota changes and GIT-symptoms in SSc. We, therefore, performed a successful feasibility trial on faecal microbiota transplantation (FMT) in SSc patients using the single-donor bacterial culture “Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)”. Based on the promising results from the feasibility trial, we aim to evaluate the safety and efficacy of FMT by ACHIM in SSc patients. (NCT04300426)Objectives:To design a clinical trial that explores the safety and efficacy of FMT in SSc patients.Methods:The ReSScue trial is a phase II, placebo-controlled, randomised 20-week, multicentre trial. The trial comprises three parts. In the induction phase (A1) lasting from week 0 to week 12, participants are randomised 1:1 to repeat infusions of 30 ml ACHIM or placebo at week 0 and 2 by gastro-duodenoscopy. In the maintenance phase (A2), all study participants will receive 30 ml ACHIM at week 12 and are followed continued blinded until week 20.For longer-term data on intervention effects and safety, the participant will be followed for a maximum extended monitoring period of 16 weeks (part B).The primary endpoint is change from baseline to week 12 in UCLA GIT scores on bloating or diarrhoea, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are changes in UCLA GIT scores (bloating, diarrhoea and total) and safety measures.Results:We aim to enrol 70 SSc patients based on the power calculations for the primary endpoint “change in worst symptom from baseline to week 12”, with a considered drop out rate of 10%. This number of patients is expected to give a power of 80% of detecting a change in mean (p=0.05, two-sided) of -5.0 (or higher) if the relating standard deviation is 0.70 or lower. The patient screening started in September 2020, and we expect the study to be completed in May 2022.Conclusion:The ReSScue-study is to our knowledge the first FMT-study in SSc. This trial will assess the safety and efficacy of FMT in SSc patients with lower GI-symptoms, possibly leading to a novel treatment approach in SSc patients.Disclosure of Interests:Håvard Fretheim Grant/research support from: Received travel bursaries from Actelion, and remuneration from Bayer., Imon Barua: None declared, Vikas Sarna: None declared, Maylen N Carstens: None declared, Oliver Distler Speakers bureau: Below, Consultant of: Below, Grant/research support from: OD has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx, Baecon Discovery, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Italfarmaco, iQone, Kymera, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Dinesh Khanna Consultant of: Abbvie, Actelion/Janssen, Acceleron Pharma, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, GSK, Horizon Pharmaceuticals, Mitsubishi Tanabe Pharma, Pfizer, Roche, Sanofi, United Therapeutics. DK is chief medical officer of Eicos Sciences, Inc., Grant/research support from: Abbvie, Actelion/Janssen, Acceleron Pharma, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, GSK, Horizon Pharmaceuticals, Mitsubishi Tanabe Pharma, Pfizer, Roche, Sanofi, United Therapeutics. DK is chief medical officer of Eicos Sciences, Inc., Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus, Forbius, Boehringer Ingelheim, Øyvind Midtvedt Shareholder of: Son of owner of ACHIM., Henriette Didriksen Speakers bureau: Travel bursary - GSK, Alvilde Dhainaut: None declared, Anna-Kristine H Halse: None declared, Gunnstein Bakland: None declared, Inge Christoffer Olsen: None declared, Maiju E Pesonen: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Medscape, Merck Sharp & Dohme, Lilly and Roche., Grant/research support from: Actelion, ARXX, Bayer, Boehringer Ingelheim, Medscape, Merck Sharp & Dohme, Lilly and Roche.

Journal of Food Research wishes to acknowledge the following individuals for their assistance with peer review of manuscripts for this issue. Their help and contributions in maintaining the quality of the journal are greatly appreciated. Journal of Food Research is recruiting reviewers for the journal. If you are interested in becoming a reviewer, we welcome you to join us. Please contact us for the application form at: jfr@ccsenet.org Reviewers for Volume 9, Number 4 &nbsp; Adele Papetti, University of Pavia, Italy Ammar Eltayeb Ali Hassan, University of Troms&oslash;, Norway Ancuta Elena Prisacaru, Stefan cel Mare University of Suceava, Romania Asima Asi Begic-Akagic, Faculty of Agriculture and Food Sciences, Bosnian Bojana Filipcev, University of Novi Sad, Serbia Cheryl Rosita Rock, California State University, United States Eganathan Palanisami, Meta Procambial Biotech Private Limited, India Elke Rauscher-Gabernig, Austrian Agency for Health and Food Safety, Austria Jintana Wiboonsirikul, Phetchaburi Rajabhat University, Thailand Jose Maria Zubeldia, Spain Juan Jos&eacute; Villaverde, INIA -National Institute for Agricultural and Food Research and Technology, Spain Lenka Kourimska, Czech University of Life Sciences Prague, Czech Republic Leonardo Mart&iacute;n P&eacute;rez, Pontifical Catholic University of Argentina, Argentina Magdalena Polak-Berecka, University of Life Sciences in Lublin, Poland Marcel Bassil, University of Balamand, Lebanese University and Benta Pharma Industries, Lebanon Miguel Elias, University of &eacute;vora, Portugal Mohd Nazrul Hisham Daud, Malaysian Agricultural Research &amp; Development Institute, Malaysia Poorna CR Yalagala, University of Illinois at Chicago, USA Salam Zahra Saleh Ahmed, National Research Centre, Egypt Sushil Kumar Singh, South Dakota State University, Brookings, USA Teodora Emilia Coldea, Univ. of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, Romania Tzortzis Nomikos, Harokopio University, Greece

BACKGROUND: Axi-cel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for treatment of relapsed/refractory (R/R) large B-cell lymphoma and is associated with high response rates and durable remissions. Recent data show that axi-cel is effective across various adverse prognostic features, namely cell of origin, disease bulkiness, and extranodal disease, among others. Hypoalbuminemia is a known adverse prognostic factor in lymphomas. It is unknown if axi-cel overcomes the adverse prognostic feature of hypoalbuminemia in R/R large B-cell or transformed follicular lymphoma. METHODS: We conducted a retrospective analysis of patients treated with axi-cel across three Mayo Clinic campuses (Rochester, Jacksonville, and Phoenix) from 06/01/2018 until 04/01/2019. The primary objective of this analysis was to assess the impact of hypoalbuminemia (defined at day 0, prior to infusion) on outcome after axi-cel therapy. RESULTS: A total of 50 (male=37, 74%) patients (pts), median age of 53 (26-67) years received axi-cel. The median number of prior lines of therapy was 3 (2-8) (Table 1). Two pts had no available serum albumin levels at time of axi-cel infusion. Seven (15%) of 48 pts had serum albumin levels lower than 3.5 g/dL (median= 3.3 g/dL (range 2.6-3.4)) and the median follow up of survivors was 7.6 (1.9-14.3) months. The best overall response rate (ORR) and complete remission (CR) rates in these pts were 57% and 57%, respectively. One (14%) patient had stable disease and 2 (29%) had disease progression. The median overall survival (OS) for pts with hypoalbuminemia was not reached. On the other hand, 41 (85%) pts had a normal serum albumin level (median=4.0 (range 3.5-5.1) g/dL) and the median follow up for survivors was 6.3 months. The best objective response rate (ORR) and complete remission (CR) rates in these pts were 82% and 44%, respectively. The median OS for pts with normal serum albumin was 14 (95%CI=6.3-29.6) months. There was no significant difference at 6-months and 1-year OS between pts with hypoalbuminemia vs. those with normal baseline serum albumin levels [6-month=100% vs. 79%(95%CI=64-93%); 1-year (100% vs. 54% (95%CI=26-82%), p=0.17] (Figure 1). All grades cytokine release syndrome (CRS) was diagnosed in all 7 pts with hypoalbuminemia (100%) and in 38 of 41 (92%) pts without hypoalbuminemia. There was no difference in the median duration of CRS between pts with or without hypoalbuminemia [6 (range 1-11) days vs 5 (range 1-19) days, p=0.89]. Neurotoxicity (all grades) was observed in 5 (71%) pts with hypoalbuminemia compared 26 (63%) with normal albumin levels. There was no statistically significant difference in median duration of neurotoxicity between pts with hypoalbuminemia and those with normal baseline albumin levels [9 (range 1-10) days vs. 3 (range 0-25) days, p= 0.72]. CONCLUSIONS: Hypoalbuminemia does not have a significant impact on the outcomes of axi-cel therapy, including the incidence of CRS or neurotoxicity. These results need to be validated in a large collaborative multicenter study. Further investigation is needed to assess the prognostic impact of severe hypoalbuminemia (<3g/dL) on axi-cel therapy. Disclosures Ansell: Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Affimed: Research Funding. Bennani:Seattle Genetics: Other: Advisory board; Kite Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board. Paludo:Verily Life Sciences: Research Funding; Celgene: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding. Tun:DTRM Biopharma: Research Funding; Mundi-pharma: Research Funding; BMS: Research Funding; Celgene: Research Funding; Curis: Research Funding; TG Therapeutics: Research Funding. Foran:Agios: Honoraria, Research Funding. Kharfan-Dabaja:Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy.

Abstract Background: Invasive fungal diseases (IFD) are on the rise due to the increasing numbers of immunosuppressed patients including those undergoing high-dose chemotherapy and hematopoietic stem-cell transplantation. Isavuconazole (ISA) is a novel, broad-spectrum antifungal triazole, available as a water-soluble prodrug in IV and oral formulations. IM is a life-threatening IFD with significant mortality and limited treatment options. Methods: The VITAL study was a Phase III, multicenter, open-label, single arm, trial conducted to evaluate efficacy and safety of ISA treatment in patients with rare IFD, including IM. Eligibility criteria and evaluated outcomes are outlined in clinicaltrials.gov, NCT00634049. Patients received IV or PO ISA 200 mg TID for 2 days followed by 200 mg/day. FungiScope™ – Global Emerging Fungal Infection Registry maintains a global web-based database on rare IFD, including IM. Entrance criteria are outlined in clinicaltrials.gov, NCT01731353. 21 patients from the VITAL study who received ISA for the primary treatment of proven/probable IM were matched (blinded to mortality status) to up-to 3 proven/probable patients with IM who received a formulation of amphotericin B entered in FungiScope™ based on 3 dichotomous risk factors: severe disease (i.e. CNS/disseminated), surgical debridement, and hematologic malignancy. All-cause mortality through day 42 was summarized. Results: 33 FungiScope™ matched controls were identified; 14 VITAL cases were matched to a single control each (n=14), 2 VITAL cases were matched to 2 controls each (n=4), and 5 VITAL cases were matched to 3 controls each (n=15). Demographics, treatments, matching criteria and mortality outcomes are shown in Table 1. The crude mortality rate (33.3%) through day 42 from the VITAL cases was similar to the mortality rate (39.4% crude; 41.3% weighted) from the matched controls of FungiScope™. Table 1 Parameter Isavuconazole VITAL Cases (n=21) FungiScopeTM Amphotericin B Matched Controls (n=33) Treatment, n (%) Isavuconazole Deoxycholate amphotericin B Liposomal amphotericin B Amphotericin B Lipid Complex 21 (100) 0 0 0 0 7 (21) 22 (67) 4 (12) Case year, range 2008–2013 2005–2013 Age, median (range) 51 (25–77) 57 (22–81) Male, n (%) 17 (81) 22 (67) Race, n (%) White Black/African American Asian 12 (57) 1 (5) 8 (38) 31 (94) 0 2 (6) Severe Disease,1 n (%) 12 (57) 13 (39) Surgical Debridement,2 n (%) 9 (43) 13 (39) Hematologic Malignancy, n (%) 11 (52) 18 (55) Crude Mortality, n (%) 7 (33.3) 13 (39.4) Weighted Mortality3 (%) Not Applicable 41.3 1 – CNS Involvement and/or Disseminated Disease 2 – Surgery performed +/– 7 days of the initiation of isavuconazole or amphotericin. 3 – Weights were applied according to the ratio of the number of controls matched to each VITAL case. Conclusions: Isavuconazole was as effective as amphotericin B formulations in the primary treatment of invasive mucormycosis based on this matched case comparison of mortality rates from the VITAL study and FungiScope™. Disclosures Vehreschild: MJGTV has served at the speakers' bureau of Pfizer, Merck, Gilead Sciences and Astellas Pharma, received research funding from 3M and Gilead Sciences and is a consultant to Berlin Chemie.: Consultancy, Research Funding, Speakers Bureau. Vehreschild:Astellas, Gilead, Infectopharm, MSD/Merck, Pfizer: Consultancy, Honoraria, Research Funding, Speakers Bureau. Marty:Astellas Pharma US, Merck, WHISCON: Honoraria, Research Funding. Perfect:Astellas, Pfizer, Merck, F26, Scynexis, Viarret: Consultancy, Research Funding. Ostrosky-Zeichner:Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Rahav:Astellas: Research Funding. Zeiher:Astellas Pharma Global Development: Employment. Lee:Astellas: Employment. Maher:Astellas: Employment. Lovell:Astellas Pharma Inc: Consultancy. Engelhardt:Basilea Pharmaceutica International Ltd: Employment. Cornely:Astellas: Consultancy, Honoraria, Research Funding, Speakers Bureau.

BackgroundTofacitinib, an oral JAK inhibitor, is indicated for the treatment of adult patients with moderate to severe active rheumatoid arthritis (RA) for which we have no real-life effectiveness data in a French RA population.ObjectivesTo describe tofacitinib effectiveness profile according to concomitant use of csDMARD in a French prospective observational study, DeFacTo.MethodsDeFacTo, is an ongoing observational study with the primary objective of identifying predictive factors of Tofacitinib maintenance in real-life RA patients. The results described here are based on a descriptive interim analysis of its effectiveness at 18 months.ResultsAmong 314 pts enrolled in the study, 301 (POP1) were included in this effectiveness analysis, including 274 (POP2) patients with follow-up ≥ 18 months on 03/15/2022 (date of analysis) with a median exposure duration of 538 [Q1; Q3: 381; 554] days. At baseline, among POP2: 168 (POP3) patients were treated with tofacitinib used concomitantly with at least one csDMARDs vs 106 (POP4) tofacitinib monotherapy. In POP3 vs POP4 respectively, 76.8% vs 84.9% were female, with a mean (± SD) age of 59.5 (10.8) vs 59.9 (12.1), median disease duration of 8.6 years [Q1;Q3: 3.2; 18.6] vs 11.1 [Q1;Q3: 5.3; 19.4)], 40.3% vs 52.4% patients had erosions, 80.5% vs 76.5% had FR+ and 77.7% vs 75.0% had ACPA+. Median CRP was 7.0 [Q1;Q3: 2.9; 18.0] vs 8.0 [Q1;Q3: 3.0; 18.1], and mean DAS28-4 CRP was 4.4 ±1.1 vs 4.7 ±1.0, in POP3 and POP4 respectively. Result showed a decrease in inflammatory markers, pain, and DAS28-CRP activity scores in both groups. At 18 months of follow-up, 24.4% and 24.5% of the pts achieved DAS28-CRP remission in POP 3 and POP 4 respectively (Table 1). Note that missing data and treatment discontinuation were considered as failures which resulted in an underestimation of LDA and remission at 18 months.Table 1.Characteristics at inclusion and effectiveness at 18 monthsBaseline, n=274At 18 month, n=274Difference from baseline to M18Variables in LS mean ± SE or % of ptsPatients with at least one concomitant csDMARD treatment (N=168)Patients without concomitant csDMARD treatment (N=106)Patients with at least one concomitant csDMARD treatment (N=168)Patients without concomitant csDMARD treatment (N=106)Patients with at least one concomitant csDMARD treatment (N=168)Patients without concomitant csDMARD treatment (N=106)PtGA*57.78 ± 1.6761.43 ± 2.0929.68 ± 2.9735.40 ± 3.38-28.10± 3.15-26.03± 3.87CRP* (mg/l)15.25± 1.8813.67± 1.455.16± 0.974.87± 0.82-10.09 ± 2.00-8.80 ± 1.52DAS28-4 CRP*4.38 ±0.094.68 ±0.102.49 ± 0.142.85 ± 0.13-1.88 ± 0.15-1.83 ± 0.16ACR-EULAR boolean criteriaⴕ3.00.912.514.29.513.3LDAⴕ, % pts- DAS28 CRP ≤3,2- DAS28 VS ≤3,211.97.13.82.835.723.237.725.523.816.133.922.7Remissionⴕ, % pts- DAS28 CRP <2,6- DAS28 VS <2,65.43.62.81.924.416.124.512.319.012.521.710.4* Missing data handled with mixed models for repeated measures ⱡ Missing data and treatment discontinuations considered failures (122 patients with missing data, 39 treatment discontinuations).ConclusionThis intermediate analysis from real-life study showed that tofacitinib in RA patients is effective with or without csDMARD.AcknowledgementsThis study was sponsored by Pfizer.Disclosure of InterestsCécile Gaujoux-Viala Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Consultant of: AbbVie; Amgen; Bristol-Myers Squibb; Celgene; Eli Lilly; Galapagos; Gilead Sciences, Inc.; Janssen; Medac; Merck-Serono; Mylan; Nordic Pharma; Novartis; Pfizer; Roche; Sandoz; Sanofi; and UCB, Andre BASCH Consultant of: Janssen, Novartis, Amgen, BMS, Abbvie, Lilly, Pfizer, MSD, UCB, Slim Lassoued: None declared, Fabienne COURY-LUCAS Consultant of: AbbVie, Bristol-Myers Squibb, Janssen, Lilly, MSD, Novartis and Pfizer, Grant/research support from: AbbVie, Biogen, Roche Chugai, Pfizer, and UCB, Meriem Kessouri Shareholder of: Pfizer, Employee of: Pfizer, Amine Saighi Shareholder of: Pfizer, Employee of: Pfizer, Yves Brault Shareholder of: Pfizer, Employee of: Pfizer, Pierre-Alexandre Squara Shareholder of: Pfizer, Employee of: Pfizer, Thierry Lequerre Consultant of: Abbvie, BMS, Boeringher, Lilly, Medac, MSD, Nordic Pharma, Novartis, Pfizer, Roche – Chugai, Sanofi, UCB, Carine Salliot Consultant of: Biogen, Lilly, Novartis, Roche Chugai, Pfizer.

Background: Treatment strategies for patients (pts) with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) continue to evolve as brentuximab vedotin (BV) and immune checkpoint inhibitors are utilized in pre-transplant salvage regimens. These new approaches are based on promising results of non-randomized trials, but it is not clear how they perform outside of clinical studies. We aimed to investigate selection patterns, toxicities, and outcomes of salvage regimens prior stem cell transplant (SCT) used currently in the United States for pts with RR cHL in the non-trial setting. Methods: We conducted a multisite, retrospective study of pts with RR cHL who were treated with a first salvage regimen (salvage 1) with intent to proceed to SCT within the past 5 years. Only pts who were treated outside of a clinical trial with salvage 1 were included. Responses were based on treating physician assessment using Revised Response Criteria for Malignant Lymphoma (Cheson et al, JCO 2014). Kaplan Meier survival curves were generated using STATA 15.0 software. Results: We identified 160 pts with diagnosis of RR cHL from 6 U.S. centers who received salvage 1 in the non-trial setting between January 2013 and January 2018. The pts' characteristics are described in Table 1. Both primary refractory pts (41%) and those with relapsed disease (59%) were included. The most common salvage 1 regimen for RR cHL was ifosfamide, carboplatin, etoposide (ICE) in 68% followed by BV monotherapy (14%) and BV+bendamustine (9%). Only 1 pt (1%) received immune checkpoint inhibitor. There were no statistically significant factors that would increase likelihood of receiving BV-containing salvage 1 including primary refractory status, age, and advanced stage. In the cohort of 59 pts who required more than one line of salvage therapy, the most common second salvage regimen (salvage 2) was BV monotherapy (42%), followed by various BV-containing combinations (22%), and ICE (19%). Only 14% of pts received 3 or more lines of salvage therapy prior to SCT. Out of 107 pts who received ICE as salvage 1, 33% were administered second salvage while out of 35 pts who received BV-containing regimen as salvage 1, 53% required salvage 2 (X2=4.7, p=0.03). Of 148 pts who ultimately underwent SCT, 52% were exposed to BV and 12% to an immune checkpoint inhibitor as part of any salvage regimen at some point prior to SCT. Response assessment to salvage 1 were available for 154 pts; 47% pts achieved complete response (CR), 30% partial response (PR), and 19% had progressive disease (PD). The responses to specific salvage 1 regimens are summarized in Table 2. For those pts undergoing salvage 2, 48% achieved CR, 19% PR and 30% had PD. Radiation was administered to 11% of pts at any point of salvage treatment prior SCT. In terms of toxicities, there were no deaths attributed to complications from any of the salvage therapies. When compared to ICE, pts undergoing BV or BV+bendamustine as salvage 1 had lower risk of neutropenic fever (0% vs 7%) and GI toxicities (10% vs 18%), but had higher risk of experiencing peripheral neuropathy (5% vs 15%). Out of 148 pts who ultimately underwent SCT, the majority had autologous (96%) and 6 (4%) pts had allogeneic SCT. The majority (73%) of patients were in CR immediately prior SCT. Four pts (3%) died due to SCT-related toxicities. BV maintenance was used in 35% of pts. Exposure to BV during salvage 1 prior SCT did not affect the likelihood of receiving BV maintenance. While there was no statistically significant difference in progression free survival (PFS) between chemotherapy only and BV-containing salvage 1, there was a trend toward improved PFS with BV-containing salvage 1 as shown in Figure 1. The 2-year PFS for chemotherapy only salvage 1 was 71% (95% CI: 60-79%) vs. 80% (95% CI: 60-91%) for BV-containing salvage treatments. Conclusion: Growing number of salvage regimens are used in RR cHL. In the current practice outside of clinical trials, 23% of RR cHL pts received BV during salvage 1. In total, 37% received more than one salvage treatment and 52% received BV as part of salvage therapy prior SCT. It is unlikely that a prospective randomized trial will be conducted to compare various salvage treatment options. However, further analysis of sub-populations who may benefit from a particular regimen or optimal treatment sequences may lead to more effective and less toxic treatment strategies for pts with RR cHL. Disclosures Svoboda: Seattle Genetics: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy; Celgene: Research Funding; Kyowa: Consultancy; Kite: Consultancy. Andreadis:Genentech: Equity Ownership, Other: Spouse is Employee; Novartis: Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Gilead: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy. Feldman:Portola Pharma: Research Funding; Eisai: Research Funding; Kyowa Hakko Kirin: Research Funding; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Roche: Research Funding; Viracta: Research Funding; Trillium: Research Funding; Pfizer: Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Corvus: Research Funding; Roche: Research Funding; Cell Medica: Research Funding; Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau. Khan:Back Bay Life Science Advisors: Honoraria; ASCO/Conquer Cancer Foundation sponsored by Gilead Sciences: Research Funding. Moskowitz:ADC Therapeutics: Consultancy; Cell Medica: Consultancy; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Merck: Research Funding; Merck: Research Funding; ADC Therapeutics: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Merck: Research Funding; Merck: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy; Incyte: Research Funding; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Merck: Research Funding; Incyte: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Incyte: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Incyte: Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; Incyte: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Portell:Roche/Genentech: Research Funding; Xencor: Research Funding; TG Therapeutics: Research Funding; Acerta/AstraZeneca: Research Funding; Kite: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Bayer: Consultancy; Amgen: Consultancy; Genentech: Consultancy, Research Funding; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; Infinity: Research Funding. Dwivedy Nasta:Merck: Consultancy, Other: data safety monitorin; 47 (Forty Seven): Research Funding; Roche: Research Funding; Rafael: Research Funding; Debiopharm: Research Funding; Aileron: Research Funding; ATARA: Research Funding; Pharmacyclics: Research Funding; Celgene: Honoraria; Millenium/takeda: Research Funding. Landsburg:Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Takeda: Research Funding; Triphase: Research Funding; Triphase: Research Funding. Barta:Mundipharma: Honoraria; Seattle Genetics: Honoraria, Research Funding; Takeda: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Mundipharma: Honoraria; Bayer: Consultancy, Research Funding; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Chong:Tessa: Consultancy; Merck: Research Funding; Novartis: Consultancy. Schuster:Acerta: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Nordic Nanovector: Consultancy, Honoraria; Genentech: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Loxo Oncology: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Patents & Royalties: Combination CAR-T and PD-1 Inhibitors, Research Funding. OffLabel Disclosure: Brentaximab vedotin containing salvage in Hodgkin lymphoma

Introduction: Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of aggressive non-Hodgkin lymphomas, with suboptimal outcomes with conventional chemotherapy. Autologous hematopoietic stem cell transplant (AHCT) is a therapeutic strategy for patients in first remission. However, progression-free survival (PFS) after AHCT is only 36-45% (d'Amore et al JCO 2012, Reimer et al JCO 2009), signifying an unmet therapeutic need for improving outcomes post-transplant. Maintenance therapy after AHCT may improve PFS. Romidepsin is a histone deacetylase (HDAC) inhibitor that is FDA approved for the treatment of relapsed/refractory T-cell lymphoma, and is a potential option for maintenance therapy. We present the results of the first multicenter study to evaluate the PFS of patients receiving maintenance therapy after upfront AHCT in PTCL patients. Methods: This was a phase 2, open-label, multicenter, investigator-initiated study in adult patients with PTCL (Table 1). 25 patients transplanted in first complete response or first partial response (CR1 or PR1) (Cohort 1) were evaluable for the primary endpoint of 2-year PFS. We enrolled another cohort (n=8) with high-risk histologies in CR/PR1 (n= 1), or transplanted in CR/PR2 or later (n=7) (Cohort 2). Patients underwent AHCT with carmustine, etoposide, cytarabine and melphalan (BEAM) conditioning. Maintenance romidepsin 14 mg/m2 was initiated between days 42-80 post AHCT, and administered every other week through 6 months, every 3 weeks through 1 year and every 4 weeks from 1 year through 2 years post AHCT. The Kaplan-Meier method was used to estimate PFS. Desired 2-year PFS was 70%. Results: Table 1 lists patient and disease characteristics. In Cohort 1, median follow up was 13.8 months (3.5 - 54.1 mon). Estimated 2-year PFS was 49% (30 - 80, 95% CI) (Figure 1). Median PFS was 20.0 months (12.0- NA, 95% CI). In Cohort 2, median follow up was 23.2 months (range, 9.1 - 35.7 months). Median PFS was 13.9 months (5.6 - NA, 95% CI). Estimated 2-year PFS was 47% (21 - 100, 95% CI). Angioimmunoblastic T-cell lymphoma (AITL) patients represented the largest subgroup within the study. 2-year PFS of these patients in Cohort 1 was 44% (20-96, 95% CI). In Cohort 1, 16 patients are off therapy (9 for disease progression, 2 for toxicity, 2 for patient choice and 3 completed therapy). Across cohorts, 5 patients required dose reduction. 6 patients experienced ≥ grade 3 toxicity (neutropenia=4, anemia=2, thrombocytopenia=2 and lymphopenia=2). 8 serious adverse events (SAEs) occurred in 6 patients after romidepsin treatment (epistaxis, fever, febrile neutropenia, hypotension, fatigue, myalgia, generalized muscle weakness, dyspnea, and CMV retinitis). Grade 2 toxicities included dysgeusia (5), neutropenia (3), anorexia (2), atrial fibrillation (1), hematuria (1), nausea (1), and fatigue (1). Grade 1 toxicities included dysgeusia (7), fatigue (4), nausea (4), anorexia (2), constipation (2), diarrhea (1), neutropenia (1), thrombocytopenia (1), and vomiting (1). Conclusions: Maintenance romidepsin was overall well-tolerated without significant additional grade 3-4 toxicity. At first assessment, the estimated median 2-year PFS in Cohort 1 of 49% does not indicate PFS improvement with romidepsin maintenance. Enrollment is complete and 9 patients in Cohort 1 are still on treatment. Final PFS will be updated. Disclosures Khan: ASCO/Conquer Cancer Foundation sponsored by Gilead Sciences: Research Funding; Back Bay Life Science Advisors: Honoraria. Shustov:Seattle Genetics, Inc.: Research Funding. Shadman:Sound Biologics: Consultancy; Sunesis: Research Funding; ADC Therapeutics: Consultancy; BeiGene: Research Funding; Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy; Celgene: Research Funding; TG Therapeutic: Research Funding; Gilead: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Acerta Pharma: Research Funding; Astra Zeneca: Consultancy; Atara Biotherapeutics: Consultancy; Mustang Bio: Research Funding. Cassaday:Kite/Gilead: Research Funding; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Other: Spouse's disclosure: employment, stock and other ownership interests; Incyte: Research Funding. Ruan:AstraZeneca: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie company: Research Funding; Juno: Consultancy; Kite: Consultancy. Moskowitz:Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Incyte: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Incyte: Research Funding; ADC Therapeutics: Consultancy; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Incyte: Research Funding; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Incyte: Research Funding; Merck: Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Cell Medica: Consultancy; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Incyte: Research Funding; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Merck: Research Funding; Cell Medica: Consultancy; Merck: Research Funding; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Incyte: Research Funding; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Cell Medica: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Cell Medica: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding. Zelenetz:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Noy:Medscape: Honoraria; Janssen: Consultancy; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding. Straus:Hope Funds for Cancer Research: Membership on an entity's Board of Directors or advisory committees; Elsevier (PracticeUpdate): Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Kumar:Seattle Genetics: Research Funding. Sauter:Celgene: Consultancy; Novartis: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy; Kite/Gilead: Consultancy; Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; GSK: Consultancy. Shah:Amgen: Research Funding; Janssen: Research Funding. Matasar:Genentech, Inc.: Consultancy, Honoraria, Other: Travel, accommodation, expenses , Research Funding; Bayer: Consultancy, Honoraria, Other; Roche: Consultancy, Honoraria, Other: Travel, accommodation, expenses , Research Funding; Merck: Consultancy, Equity Ownership; Juno Therapeutics: Consultancy; Teva: Consultancy; Rocket Medical: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel, accomodation, expenses, Research Funding; Daiichi Sankyo: Consultancy; GlaxoSmithKline: Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Bayer: Other: Travel, accommodation, expenses. Van Besien:Miltenyi Biotec: Research Funding. Giralt:Sanofi: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy. Horwitz:Mundipharma: Consultancy; Astex: Consultancy; Trillium: Research Funding; Kyowa Hakko Kirin: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Portola: Consultancy; Aileron: Research Funding; Miragen: Consultancy; Celgene: Consultancy, Research Funding; Kura: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Portola: Consultancy; ADCT Therapeutics: Research Funding; Innate Pharma: Consultancy; Affimed: Consultancy; Aileron: Research Funding; Seattle Genetics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Infinity/Verastem: Consultancy, Research Funding; ADCT Therapeutics: Research Funding; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astex: Consultancy; Innate Pharma: Consultancy; Kyowa Hakko Kirin: Consultancy; Seattle Genetics: Consultancy, Research Funding; Mundipharma: Consultancy; Affimed: Consultancy; Forty-Seven: Research Funding; Portola: Consultancy; Trillium: Research Funding; Affimed: Consultancy; Miragen: Consultancy; Astex: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Miragen: Consultancy; Astex: Consultancy; Infinity/Verastem: Consultancy, Research Funding; Mundipharma: Consultancy; Celgene: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Kura: Consultancy; Corvus Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Forty-Seven: Research Funding; Portola: Consultancy; Mundipharma: Consultancy; Aileron: Research Funding; Kura: Consultancy; Celgene: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Infinity/Verastem: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Kura: Consultancy; Innate Pharma: Consultancy; Aileron: Research Funding; Kyowa Hakko Kirin: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Miragen: Consultancy; Affimed: Consultancy; ADCT Therapeutics: Research Funding; Trillium: Research Funding; Kyowa Hakko Kirin: Consultancy; Forty-Seven: Research Funding; Forty-Seven: Research Funding; Trillium: Research Funding; Innate Pharma: Consultancy; ADCT Therapeutics: Research Funding. OffLabel Disclosure: Romidepsin has been FDA approved for the treatment of relapsed/refractory cutaneous T-cell lymphoma and has accelerated approval for treatment of relapsed/refractory peripheral T cell lymphoma. We are studying its use as maintenance therapy after autologous stem cell transplant.

Background: Myelofibrosis (MF) is characterized by bone marrow fibrosis (BMF) and ineffective extramedullary hematopoiesis resulting in splenomegaly and debilitating symptoms. An activating Janus kinase 2 (JAK2) mutation (V617F) has been frequently observed in MF. Ruxolitinib (a JAK1/JAK2 inhibitor) reduces splenomegaly and improves constitutional symptoms, but appears to offer a modest reduction of BMF. Patients with MF who are intolerant to JAK inhibitors or their components, or for whom JAK inhibitors have failed, have limited treatment options. The Proviral Integration site of Moloney murine leukemia virus (PIM) serine/threonine kinases are overexpressed in hematological malignancies. Because PIM kinase expression is regulated by JAK2 signaling, PIM kinase inhibition is a potential therapeutic target for JAK2 mutant-driven malignancies, such as MF. TP-3654, an investigational agent, has been shown to reduce proliferation and increase apoptosis in murine and human hematopoietic cells expressing the JAK2V617F mutation. TP-3654 alone reduced leukocytosis and spleen size in an in vivo murine model of JAK2V617F-induced MF, as well as an apparent reduction of BMF. A phase 1 study is being conducted to evaluate TP-3654 monotherapy in patients with MF. Study Design and Methods: This phase 1, multicenter, dose-escalation, open-label study is evaluating TP-3654 monotherapy in patients with MF who previously failed a JAK inhibitor or who are ineligible to receive ruxolitinib or fedratinib (NCT04176198). Primary objectives are to determine the incidence of dose-limiting toxicities (DLT) at escalated doses of TP-3654 and treatment emergent adverse events. Secondary objectives are to determine QT interval changes, establish the pharmacokinetic profile, and assess preliminary disease activity. Exploratory objectives are pharmacodynamic markers in peripheral blood and bone marrow biopsy samples. Eligible patients have a primary or secondary MF (post-polycythemia vera-MF/post-essential thrombocythemia-MF) based on the World Health Organization diagnostic criteria and intermediate-2 or high-risk primary or secondary MF based on the Dynamic International Prognostic Scoring System; previously failed, or are ineligible to receive, treatment with a JAK inhibitor; grade ≥2 MF, as confirmed by BM biopsy ≤12 weeks prior to screening; have a platelet count &gt;50x109/L, absolute neutrophil count ≥1x109/L, hemoglobin level ≥8 g/L, peripheral blood blast counts &lt;10%, Eastern Cooperative Oncology Group performance status ≤2, life expectancy ≥3 months, and adequate renal and hepatic function; have spleen length ≥5 cm by palpation or spleen volume ≥450 cm3 by computerized tomography/magnetic resonance imaging, and show ≥2 measurable symptoms per the MF Symptom Assessment Form, version 4.0. Patients must not have received prior systemic antineoplastic therapy or any experimental therapy within 14 days or 5 half-lives before TP-3654; had major surgery ≤2 weeks before first study dose; have had splenic irradiation ≤6 months prior to screening; have acute myeloid leukemia or myelodysplastic syndrome; or had prior stem cell transplantation (SCT) or be eligible for allogeneic bone marrow or SCT. Enrollment of approximately 50 patients is planned. Patients will receive oral TP-3654. Dose-escalation will be performed using a Bayesian logistic regression model with escalation with overdose control. Adverse events occurring during the first cycle will be considered in the determination of the maximum tolerated dose (MTD). Dose escalation will continue until identification of the MTD or a suitable recommended phase 2 dose. This study is currently recruiting patients. Disclosures Lebedinsky: Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment. Anthony:Exact Sciences: Consultancy; Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment. Mohi:Tolero Pharmaceuticals Inc.: Research Funding. Yang:Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment. Mei:Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment. Braendle:Sumitomo Dainippon Pharma Oncology, Inc.: Current Employment.

Introduction: With the expanding use of CAR-T cell therapy, which is associated with serious adverse effects (AEs), there is a need to characterize the patient's experience over time to guide patient/provider education, and help optimize symptom management. This study reports on longitudinal evaluation of patient-reported quality of life (QOL) and symptom burden of CAR-T cell therapy compared with established forms of cellular therapy i.e autologous stem cell transplant (autoSCT) and allogeneic SCT (alloSCT). Methods: Patients with hematologic malignancies were prospectively recruited in three cohorts: CAR-T, autoSCT and alloSCT. The primary endpoint was change in QOL from baseline, using the FACT-G questionnaire. Secondary endpoints were patient-reported AEs (PRO-AEs) using 7 items from the PRO-CTCAE and assessment of cognition/memory using the NeuroQOLv2 questionnaire. PRO-CTCAE data was graded using a composite score (combining frequency, severity, and interference) and rates, using a method adjusting for pre-existing baseline symptoms, were compared using Fisher's exact test. We also evaluated the time profile of PRO-AEs using the Toxicity over Time (ToxT) approach, a longitudinal approach to AE analysis (Thanarajasingam Lancet Onc 2016). Patients completed questionnaires at baseline, week 2 and monthly thereafter. Results: From 07/2018 to 06/2019, 93 patients were recruited (CAR-T: 20; autoSCT: 37; alloSCT: 36). At data cut-off, week 2 and months 1, 2 and 3 data were available in 74, 62, 46 and 35 patients, respectively. There was no difference in patient age across the 3 groups (median age 63, range 23-77; p=0.26). Baseline QOL by FACT-G total score (mean=83.4, SD=14.7; p=0.77), side effect bother by FACT-G GP5 (66/93 [71%] a little bit or less; p=0.72), activities and function (70/93 [75%] fairly normal activities or no limitations; p=0.68) and cognition by NeuroQOL t-score (mean=52.2, SD=8.13; p=0.39) were similar across 3 groups at baseline. The CAR-T group experienced significantly less worsening in QOL (FACT-G) than both autoSCT and alloSCT groups (Fig. 1a). Worsening in overall QOL nadired at week 2, after which QOL gradually returned to baseline in all groups. When comparing changes from baseline in overall QOL, statistically significant differences between groups were evident at week 2 (CAR-T vs autoSCT p&lt;0.001; vs alloSCT p&lt;0.001), month 1 (CAR-T vs autoSCT p=0.02; vs alloSCT p=0.003), month 2 (CAR-T vs autoSCT p=0.02; vs alloSCT p=0.001) and month 3 (CAR-T vs autoSCT p=NS; vs alloSCT p=0.03). Results for physical (Fig. 1b) and functional well-being (WB) were similar, with significantly less QOL worsening at week 2 in CAR-T vs autoSCT and alloSCT groups. The most common PRO-AEs (Table 1) in the CAR-T group were decreased appetite (59%), diarrhea (53%) and fatigue (44%). There was no statistically significant difference in the PRO-AEs between CAR-T and autoSCT groups. However, patients undergoing alloSCT had significantly higher proportion of PRO-AEs vs the CAR-T group, except for neuropathy and sad feelings. AutoSCT and alloSCT groups had significant worsening of FACT-G side effect bother (GP5) at week 2, which was significantly different from that of the CAR-T group, following which the side effect bother gradually returned to baseline. (Fig. 1c) This was the first application of ToxT to PRO-CTCAE data (graphs not shown). Bar charts of maximum grade frequency and stream plots of mean grade over time demonstrate that mouth sores, fatigue, diarrhea and decreased appetite peak at week 2 and improve by month 3, and are of lesser severity in the CAR-T vs autoSCT and alloSCT groups. The trajectory of maximum grade across all PRO-AEs was similar by group as overall side effect burden by FACT-G GP5. Heatmap visualization demonstrated significant intra-patient variability and allowed inspection of data completeness. No difference in cognition and memory was observed across the three groups over the first three months. (Fig. 1d) Conclusion: This study is the first to our knowledge to provide comprehensive PRO data comparing QOL, patient-reported AEs and cognition in CAR-T cell therapy vs. auto- and alloSCT, and the first application of ToxT to PRO-CTCAE data. Short-term QOL, including physical and functional WB domains was better in the CAR-T group vs. SCT groups. These data can serve as a guide for patient education and symptom management in CAR-T cell therapy. Co-senior authors: SKK & ACD Disclosures Paludo: Celgene: Research Funding; Celgene: Research Funding; Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding. Gertz:Johnson and Johnson: Speakers Bureau; Celgene: Consultancy; Appellis: Consultancy; Amyloidosis Foundation: Research Funding; DAVA oncology: Speakers Bureau; Physicians Education Resource: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Medscape: Consultancy, Speakers Bureau; Prothena Biosciences Inc: Consultancy; Teva: Speakers Bureau; Research to Practice: Consultancy; Annexon: Consultancy; Alnylam: Consultancy; International Waldenstrom Foundation: Research Funding; Ionis/Akcea: Consultancy; Spectrum: Consultancy, Research Funding; i3Health: Other: Development of educational programs and materials; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Springer Publishing: Patents & Royalties. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Ansell:Trillium: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding. Bennani:Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Kite Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

BackgroundUpadacitinib (UPA) improved symptoms in patients (pts) with psoriatic arthritis (PsA) with prior inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (nbDMARD-IR) through week (wk) 104 or 2 years of treatment in SELECT-PsA 1[1].ObjectivesTo evaluate efficacy and safety of UPA vs adalimumab (ADA) through wk 152 or 3 years from the ongoing long-term open-label extension of SELECT-PsA 1.MethodsPts were randomized to receive UPA 15 mg (UPA15) or UPA 30 mg (UPA30) once daily, ADA 40 mg (ADA) every other wk, or placebo (PBO). At wk 24, PBO pts switched to UPA15 or UPA30. Following approval of UPA15, the protocol was amended so pts on UPA30 switched to UPA15 (earliest at wk 104). Efficacy was assessed through wk 152, and safety through June 13, 2022.ResultsOf 1704 pts randomized, 911 completed 152 wks of treatment. The proportions of pts achieving.≥20%/50%/70% improvement in American College of Rheumatology criteria (ACR20/50/70), minimal disease activity (MDA), and ≥75%/90%/100% improvement in Psoriasis Area and Severity Index at wk 152 were generally consistent with those at wk 1041. UPA had greater ACR20/50/70 and MDA responses vs ADA, and a greater mean change from baseline (BL) in Health Assessment Questionnaire-Disability Index, pt’s assessment of pain, and Bath Ankylosing Spondylitis Disease Activity Index vs ADA. Change from BL in modified total Sharp/van der Heijde score were similar between UPA30 and ADA, and numerically higher with UPA15(Table 1). The overall UPA safety profile remained unchanged (Figure 1)[1,2]. UPA had numerically higher rates of serious infection (SI), herpes zoster (HZ), anemia, lymphopenia, creatine phosphokinase (CPK) elevation, and non-melanoma skin cancer (NMSC) vs ADA. Increases for SI, HZ, anemia, and CPK elevation with UPA were dose dependent. Rates of major adverse cardiovascular events, venous thromboembolism, and malignancy excluding NMSC were low and generally similar across groups. The most common cause of death was COVID-19.ConclusionEfficacy of UPA in nbDMARD-IR pts with PsA was maintained through 3 years of treatment. No new safety signals were identified.References[1]McInnes IB, et al. Rheumatol Ther 2022;1–18 [Epub ahead of print].[2]McInnes IB, et al. RMD Open 2021;7(3):e001838.Table 1.Efficacy endpoints at wk 152UPA15 (n=429)UPA30a(n=423)ADA (n=429)Proportion of pts (%)NRIAONRIAONRIAOACR20/50/7064.6/52.0/35.9*89.8/71.6/48.263.1/54.1*/35.787.9/74.4/47.861.1/46.6/28.786.2/65.2/39.8Minimal diseaseactivity37.555.143.5*60.335.950.2PASI75/90/100b50.5/42.5/32.269.2/58.5/43.458.1/46.7/37.678.6/63.5/50.954.0/40.8/30.379.6/59.9/44.6Resolution of enthesitis by Leeds EnthesitisIndexc50.475.248.973.846.077.0Resolution of dactylitis by Leeds DactylitisIndexd65.495.266.197.965.497.1Change from BLeMMRMAOMMRMAOMMRMAOHealth Assessment Questionnaire-Disability Index-0.51-0.55-0.53*-0.58-0.45-0.49Pt’s assessment of pain (numericrating scale)-3.3*-3.5-3.3*-3.6-2.8-3.0Bath Ankylosing Spondylitis Disease ActivityIndexf-3.09-3.27-3.16-3.54-2.81-2.71Modified totalSharp/van derHeijde score0.210.190.050.040.090.09aFollowing a protocol amendment, all pts on UPA30 switched to UPA15 (earliest switch at wk 104); data are presented by originally randomized group.bPts with psoriasis affecting ≥3% of body surface area at BL.cPts with LEI >0 at BL; resolution LEI=0.dPts with LDI >0 at BL; resolution LDI=0.eData shown as MMRM (least squares mean) and AO (mean).fPts with psoriatic spondylitis at BL. n value ranges: UPA15 (99–429), UPA30 (95–423), ADA (89–429). Nominal *p<0.05 UPA vs ADA.ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; ADA, adalimumab; AO, as observed; BL, baseline; MMRM, mixed effect model repeated measurement; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; pt, patient; UPA15/30, upadacitinib 15/30 mg once daily; wk, weekAcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, and the review and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of InterestsIain McInnes Grant/research support from: AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Eli Lilly, Evelo, Causeway Therapeutics, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Employee of: AbbVie and may hold stock or options, Marina Magrey Consultant of: BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, BMS, and UCB Pharma, Joseph F. Merola Consultant of: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Celgene, Dermavant, Eli Lilly, EMD Sorono, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, and UCB Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Grant/research support from: AbbVie, Adiga Life Sciences, Amgen, Bristol Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB; and has received honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, and UCB Pharma, Yihan Li Employee of: AbbVie and may hold stock or options, Yanxi Liu Employee of: AbbVie and may hold stock or options, Jianzhong Liu Employee of: AbbVie and may hold stock or options, Ralph Lippe Employee of: AbbVie and may hold stock or options, Peter Wung Employee of: AbbVie and may hold stock or options.

INTRODUCTION: Historically chemoimmunotherapy has been the standard of care in the treatment of first-line (1L) chronic lymphocytic leukemia (CLL). More recently several effective oral targeted agents, such as ibrutinib-based regimens, have provided effective chemotherapy-free treatment options in CLL. However, these therapies require continuous treatment until disease progression. Recently FDA approved (May 2019), venetoclax plus obinutuzumab (VenG) is a highly effective chemotherapy-free therapy that is used over a 12-month fixed treatment duration (Fischer et al, N Eng J Med 2019). The objective of this study is to estimate the cost-effectiveness of VenG in the treatment of 1L CLL from a US-payer perspective. METHODS: A three-state partitioned-survival model was used to extrapolate progression-free survival and overall survival over a lifetime horizon (20 years). Cost-effectiveness was estimated by comparing a 12-month fixed duration of VenG versus (vs.) chlorambucil-obinutuzumab (ClbG) based on the CLL14 clinical trial (NCT02242942). Other comparators included treat-to-progression therapies, such as ibrutinib (IBR), IBR + rituximab (IR), and IBR + G (IG), and a 6-month course of bendamustine + rituximab (BR). Using a network meta-analysis, the relative efficacy of VenG and ClbG vs. other selected comparators was estimated. Health state utilities and adverse event (AE) disutilities were derived from a systematic literature review and published health-technology assessment reports. To generate total quality-adjusted life years (QALYs), these health state utilities and AE disutilities were applied to the relative efficacy data. US-specific costs included those for CLL treatment, routine care and monitoring, AEs, disease progression (including subsequent treatment), and end-of-life care. Cost-effectiveness results are presented in terms of incremental cost per QALY. A new treatment that is both lower in total cost and more efficacious (in QALYs) vs. identified comparator treatments is described as being "dominant". Uncertainty in the model was tested through deterministic, probabilistic, and scenario analyses. RESULTS: The benefits in the cost-effectiveness model (CEM) were measured in terms of total discounted QALYs which were 6.47 for VenG, 6.12 for ClbG, 6.11 for IBR, 6.08 for IR, 6.41 for IG, and 5.98 for BR. The total discounted costs incurred by VenG and ClbG were $322,613 and $847,571, respectively. IBR-based treat-to-progression regimens incurred total discounted costs of $1,485,368 for IBR, $1,447,010 for IR, and $1,988,706 for IG. BR incurred total discounted costs of $808,756. Compared to these regimens, VenG is less costly (incremental cost ranges between: -$1,666,093 to -$486,143). The incremental discounted QALYs of VenG was: 0.36 vs. GC, 0.49 vs. BR, 0.37 vs. IBR, 0.06 vs. IG, and 0.39 vs. IR. Thus, VenG with a 12-month fixed duration, has lower total costs and is more efficacious ("dominant") over all comparators in the CEM. The probabilistic sensitivity analysis results were in line with the deterministic results. Sensitivity analysis indicated the post-progression survival utility was the most influential parameter on the model outcomes. As the CLL14 trial data matures, these cost-effectiveness estimates may change and additional scenarios for post-progression survival for VenG will be explored. Updated results will be presented. CONCLUSIONS: VenG is projected to be cost-effective vs. ClbG within accepted US cost-effectiveness thresholds. Compared with BR and IBR-based treat-to-progression regimens (IBR, IR, and IG), a 12-month fixed-duration treatment option with VenG seems cost saving and more efficacious based on the CEM. Taken together, VenG appears to be a cost-effective standard therapy for 1L CLL patients. Disclosures Davids: AbbVie, Acerta Pharma, Adaptive, Biotechnologies, Astra-Zeneca, Genentech, Gilead Sciences, Janssen, Pharmacyclics, TG therapeutics: Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; AbbVie, Astra-Zeneca, Genentech, Janssen, MEI, Pharmacyclics, Syros Pharmaceuticals, Verastem: Consultancy; Acerta Pharma, Ascentage Pharma, Genentech, MEI pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, Verastem: Research Funding. Ravelo:Genentech: Employment, Equity Ownership. Shapouri:Roche: Equity Ownership; Genentech, Inc.: Employment. Manzoor:AbbVie: Employment, Other: and may hold stock or stock options. Sail:AbbVie: Employment, Other: and may hold stock or stock options. Van de Wetering:AbbVie: Consultancy. Hallek:Roche, Gilead Sciences, Inc., Mundipharma, Janssen, Celgene, Pharmacyclics, AbbVie: Honoraria, Research Funding, Speakers Bureau.

Patients with atopic dermatitis not on systemic therapy have high rates of severe, uncontrolled disease and considerable impact on quality of life Eric Simpson1, Christian Fenske2, Alvin Li3, Zach Dawson2, Yolanda Muñoz Maldonado3, Kaylee Ho3, Kayla Callahan3, Linda Stein Gold4, Seemal Desai5, Alexandra Golant6, Douglas DiRuggiero7, Jonathan I Silverberg8 1Oregon Health & Science University, Portland, Oregon, USA; 2Eli Lilly and Company, Indianapolis, USA; 3CorEvitas LLC, Waltham, Massachusetts, USA; 4Henry Ford Health System, Michigan, USA; 5Innovative Dermatology, PA, Texas, USA; 5The University of Texas Southwestern Medical, Dallas, Texas, USA; 6Icahn School of Medicine at Mount Sinai, New York, USA; 7Skin Cancer and Cosmetic Dermatology Center, Rome, Georgia, USA; 8George Washington University School of Medicine and Health Sciences, Washington, DC, USA Background: Decision to initiate a new systemic therapy (ST) among patients with atopic dermatitis (AD) is complex. This cross-sectional study explored overall disease burden, sociodemographic and clinical characteristics, and disease activity among patients with moderate-to-severe AD. Methods: Adult patients with AD who had a vIGA-ADTM score ≥3 and Eczema Area Severity Index (EASI) score ≥12 at enrollment were identified from the prospective, longitudinal CorEvitas AD Registry between 07/21/2020 and 12/31/2022. Included patients were newly prescribed an eligible ST (ST group) or not prescribed an eligible ST (non-ST group) at enrollment. Patients on ST before enrollment were excluded. Sociodemographic characteristics, disease features, severity measures (vIGA-ADTM [0–4]; body surface area (BSA) [0–100%]; EASI [0–72]), and patient-reported outcomes (PROs) were assessed. PROs included Dermatology Life Quality Index (DLQI) [0-30], Itch/Pruritus Numeric Rating Scale [0-10], Patient-Oriented Eczema Measure (POEM) [0-26], and AD Control Tool (ADCT) [<7 controlled, >7 not controlled]. Differences in means or proportions of characteristics among ST and non-ST groups were summarized using effect sizes (ES). Results: The study included 673 (mean age=50.7 years, 55.6% female) patients who were newly prescribed ST and 229 (47.8 years, 51.3%) who were not prescribed ST. The overall distribution of race (Whites 70.4% vs. 60.5%, Asians 8.6% vs. 17.5%, Black 13.7% vs. 8.3%, Other 7.3% vs. 13.6%; ES=0.17) and geographic region (West 8.5% vs. 28.4%, South 32.1% vs. 15.7%; ES=0.27) had small differences between the ST and non-ST groups. More patients (n=402 [59.7%]) in the ST group had severe AD (vIGA-ADTM=4), whereas moderate AD (vIGA-ADTM=3) was more common (n=137 [59.8%]) in the non-ST group. Higher disease severity was reported in the ST group versus non-ST group: BSA (mean [SD]: 41.6% [17.1] vs. 31.5% [16.0]; ES=0.61) and EASI (24.3 [10.1] vs. 19.8 [8.6]; ES=0.47). Mean [SD] PRO measures were also higher in the ST group compared to non-ST group: DLQI (11.7 [7.5] vs. 10.4 [7.9]; ES=0.17), mean peak pruritus in the past 24 hours (6.8 [2.9] vs. 6.1 [3.1]; ES=0.25), POEM (17.8 [7.1] vs. 16.6 [7.5]; ES=0.17), and ADCT (14.4 [6.1] vs. 13.0 [6.7]; ES=0.21). Conclusion: Patients not initiating ST have high rates of severe, uncontrolled AD, and considerable burden from their disease, indicating potential delayed or undertreatment. Understanding the factors that influence the decision to escalate therapy in systemic-eligible patients is important for improving care of AD. Disclosures Eric Simpson: Dr. Simpson reports personal fees from Advances in Cosmetic Medical Derm Hawaii LLC, AbbVie, Amgen, AOBiome LLC, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharma, Boehringer-Ingelheim USA, Inc., Boston Consulting Group, Bristol Myers Squibb – BMS, Collective Acumen LLC (CA), CorEvitas, Dermira, Eli Lilly, Evelo Biosciences, Evidera, ExcerptaMedica, FIDE, Forte Bio RX, Galderma, GlaxoSmithKline, Incyte, Janssen, Johnson & Johnson, Kyowa Kirin Pharmaceutical Development, Leo Pharma, Medscape LLC, Merck, MauiDerm, MLG Operating, MJH holding, Pfizer, Physicians World LLC, PRImE, Regeneron, Revolutionizing Atopic Dermatitis Inc., Roivant, Sanofi-Genzyme, Trevi therapeutics, Valeant, Vindico Medical education, WebMD. Dr. Simpson reports grants (or serves as Principal investigator role) from AbbVie, Acrotech Biopharma Inc., Amgen, Arcutis, Aslan, Castle Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Kirin, National Jewish Health, Leo, Pfizer, Regeneron, Sanofi, and Target RWE. These potential conflicts of interest have been reviewed and managed by OHSU. Christian Fenske: Employment and stockholder, Eli Lilly and Company. Alvin Li: Employee of CorEvitas, LLC and stockholder, Eli Lilly and Company. Zach Dawson: Employment and stockholder, Eli Lilly and Company. Yolanda Muñoz Maldonado: Employee of CorEvitas, LLC. Kaylee Ho: Employee of CorEvitas, LLC. Kayla Callahan: Employee of CorEvitas, LLC and stockholder, Eli Lilly and Company. Linda Stein Gold: Investigator, advisor and/or speaker for Lilly, BMS, UCB, Pfizer, Sanofi, Regeneron, Dermavant, Arcutis, Sun, Incyte, Leo, Aslan. Seemal Desai: Dr. Desai is currently performing paid consulting services. He has previously been an advisor for Lilly and also performed consulting and/or clinical for multiple organizations. Alexandra Golant: Dr. Golant has received consulting or speaker fees from: Regeneron, Sanofi, AbbVie, Incyte, Dermavant, Lilly, Leo Pharma, Arcutis, Janssen, Amgen, Pfizer. Douglas DiRuggiero: Industry speaker bureau and advisory boards: AbbVie, Amgen, Arcutis, BMS, Incyte, Janssen, Lilly, Novartis, Sanofi/Regeneron, UCB. Jonathan I. Silverberg: Jonathan Silverberg has received honoraria as a consultant and/or advisory board member for AbbVie, AOBiome, Arcutis, Alamar, Amgen, Arena, Asana, Aslan, BioMX, Biosion, Bodewell, Boehringer-Ingelheim, Cara, Castle Biosciences, Celgene, Connect Biopharma, Dermavant, Dermira, Dermtech, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Kiniksa, Leo Pharma, Menlo, Novartis, Optum, Pfizer, RAPT, Regeneron, Sanofi-Genzyme, Shaperon, Union; speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme; institution received grants from Galderma, Pfizer.

Background:Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects 1% of the world’s population. Several key biological functions are dysregulated in RA, manifesting clinically as pain, fatigue, and synovitis, with articular destruction, organ-based comorbidities, and functional decline. Defining immune dysregulation in the peripheral blood of patients (pts) with RA will help inform future work to assess the extent to which immune homeostasis can be therapeutically achieved for these pts.Objectives:To identify baseline molecular characteristics of the peripheral immune system, at the level of individual immune cell subsets, in pts with RA recruited to clinical trials of the oral, selective Janus kinase 1 (JAK1) inhibitor, filgotinib.Methods:Peripheral blood mononuclear cells (PBMC) were collected from 324 pts with moderate to severely active RA, who had an inadequate response to methotrexate ([MTX], FINCH-1;NCT02889796; n=109) or who were MTX naïve (FINCH-3;NCT02886728; n=215). PBMC were also collected from 50 demographically matched healthy volunteers (HV). The Immune Profiler platform was used to sort PBMC into 24 immune cell subsets, then quantify their gene expression and chromatin accessibility using RNA-seq and the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), respectively. Differentially expressed genes (DEGs) and differentially accessible regions (DARs) were identified among immune cell subsets from pts with RA versus HV. Gene set signature scores of Molecular Signatures Database hallmark pathways were calculated using single sample gene set enrichment analysis (ssGSEA) to examine differences in pathway activity between groups.Results:A total of 14,500 sequencing datasets were generated from the pt and HV immune cell subsets. Among these, over 26,000 DEGs and 220,000 DARs were identified in RA versus HV (false discovery rate <0.05) across the 24 immune cell subsets. DEGs were identified in all immune cell subsets tested and were most pronounced in natural killer (NK) subsets; most DARs were detected in myeloid and NK subsets. ssGSEA revealed differential pathway signaling in RA versus HV across multiple functions at the immune cell subset level. Myeloid subsets from pts with RA often showed elevated pathway activities versus HV whereas B, T and NK subsets showed a general decrease. In particular, monocyte populations from pts with RA versus HV had elevated pathway activities involved in inflammatory response and interleukin-6/Janus kinase/signal transducer and activator of transcription 3 signaling. The B, T and NK subsets showed a general decrease in tumor necrosis factor-α signaling; conversely, monocyte subsets showed an increase. Prior MTX exposure did not have a notable impact on the detected molecular profile.Conclusion:Differences in gene expression, hallmark pathway activity, and chromatin accessibility were identified in RA versus HV at the immune cell subset level. Significant contributions to differences in chromatin accessibility identified in the myeloid and NK cell populations suggest that there are more active regulatory sequences in these cell types that are associated with RA. Further investigations based on these findings may increase understanding of the immune regulatory paradigm in the context of RA.Acknowledgments:This study was funded by Gilead Sciences, Inc. Editorial support was provided by Fishawack Communications Inc and funded by Gilead Sciences, Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Jinfeng Liu Shareholder of: Gilead Sciences Inc., Roche, Employee of: Gilead Sciences Inc., Luting Zhuo Employee of: Gilead Sciences Inc., Yuan Tian Employee of: Gilead Sciences Inc., Thomas Snyder Employee of: Verily Life Sciences, Charlie Kim Employee of: Verily Life Sciences, Pouya Kheradpour Employee of: Verily Life Sciences, Kat Drake Employee of: Verily Life Sciences, Sam Kim Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc., Rachael E. Hawtin Shareholder of: Gilead Sciences Inc., Employee of: Gilead Sciences Inc.

Introduction: Bruton Tyrosine Kinase inhibitors (BTKis) have transformed the treatment of patients with chronic lymphocytic leukemia (CLL) and other B-cell malignancies by inducing durable responses, improving quality of life and prolonging overall survival. Prolonged use of BTKi in the real-world setting is limited by toxicity and acquired resistance. Discontinuation rates for BTKis may be as high as 40% in relapsed/refractory CLL, with BTK C481-mediated resistance evident in many progressing patients. Alternative therapies such as venetoclax are associated with on-target (BCL2) acquired resistance. We hypothesized that a selective, non-covalent BTKi would benefit patients with B-cell malignancies in the setting of acquired resistance and/ or unacceptable toxicities following an irreversible BTKi. LOXO-305 is a next-generation, highly selective, oral, non-covalent BTKi that inhibits wild-type and C481-mutated BTK preclinically. Here, we report results from a first-in-human, proof-of-concept phase 1 trial in patients with B-cell malignancies. Methods: This multicenter phase 1/2 trial (NCT 03740529) enrolled patients with advanced B-cell malignancies who had failed or were intolerant to &gt; 2 prior therapies. LOXO-305 was dosed orally in 28-day cycles, using a standard 3+3 dose-escalation design with a primary endpoint of MTD/RP2D identification. Results: As of 26 July 2019, 13 patients (9 CLL and 4 MCL) were enrolled to 3 dose levels: 25mg (n=5), 50mg (n=5) and 100mg (n=3) QD. Median age was 65 (range 51-79) years and the median number of prior therapies was 3 (range 2-6). 12 patients (8 CLL, 4 MCL) received prior chemotherapy + anti-CD20 antibody; 2 MCL patients underwent prior autologous stem cell transplantation; 5 CLL patients received prior umbralisib; 10 patients (7 CLL, 3 MCL) received prior ibrutinib (5 intolerant, 5 relapsed), including 1 who had also received venetoclax. 6 CLL patients displayed high-risk genetic features, including unmutated IGHV (4), complex karyotype (4) and del17p (3). Molecular characterization was available in 7 patients (6 CLL, 1 MCL) and revealed: BTK C481S mutations (in 2 CLL patients post-ibrutinib), a BCL2 G101V mutation (in a CLL patient post-venetoclax), and a TP53 mutation (in an MCL patient post-ibrutinib). At doses ≥50 mg QD, LOXO-305 exposure exceeded the calculated IC90 for wild-type and C481S mutated BTK. No DLTs were reported and all TEAEs are grade 1-2. Clinical activity was noted within the first cycle of therapy and at the first dose level of 25mg QD. The first eight patients were evaluable for initial response and 7 tumor responses (87.5%) were observed (by disease-defined criteria): 5/5 CLL patients (1 PR and 4 PR-L including one with BTK C481S mutation after ibrutinib and one with BCL2 G101V mutation after venetoclax) and 2/3 MCL patients (2 PR and 1 PD with a preexisting TP53 mutation). 2 additional CLL patients were awaiting initial radiologic assessment but had already demonstrated treatment-induced lymphocytosis. 12/13 patients remain on therapy, the longest 5+ months. Conclusion: Phase 1 data with LOXO-305 demonstrate a favorable safety profile and provide proof-of-concept evidence of efficacy in heavily pretreated CLL and MCL patients, including patients with acquired resistance to available BTKis and venetoclax. Disclosures Mato: DTRM Biopharma: Research Funding; Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Gilead: Research Funding; Acerta: Consultancy; Janssen: Consultancy; TG Therapeutics: Consultancy, Other: DSMB member , Research Funding; Celgene: Consultancy; Sunesis: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; LOXO: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Research Funding. Flinn:F. Hoffmann-La Roche Ltd: Research Funding; Acerta Pharma, Agios, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Genentech, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Janssen, Karyopharm Therapeutics, Kite Pharma, Novartis, Pharmacyclics, Portola Pharmaceuticals: Research Funding; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; AbbVie, Seattle Genetics, TG Therapeutics, Verastem: Consultancy. Pagel:AstraZeneca: Consultancy; Gilead Sciences: Consultancy; Pharmacyclics: Consultancy. Brown:Teva: Honoraria; Janssen: Honoraria; Sunesis: Consultancy; Juno/Celgene: Consultancy; Gilead: Consultancy, Research Funding; Dynamo Therapeutics: Consultancy; Genentech/Roche: Consultancy; Pharmacyclics: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Loxo: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Sun Pharmaceuticals: Research Funding; Verastem: Consultancy, Research Funding; TG Therapeutics: Consultancy; Octapharma: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; Catapult Therapeutics: Consultancy; Acerta Pharma: Consultancy; Invectys: Other: Data safety monitoring board; Morphosys: Other: Data safety monitoring board; AbbVie: Consultancy. Cheah:Roche, Janssen, MSD, Gilead, Loxo Oncology, Acerta, BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene, Roche, Abbvie: Research Funding; Roche: Other: Travel expenses. Coombs:Medscape: Honoraria; Covance: Consultancy; Cowen & Co.: Consultancy; H3 Biomedicine: Honoraria; Dedham Group: Consultancy; Loxo: Honoraria; Abbvie: Consultancy; Octopharma: Honoraria; Pharmacyclics: Honoraria. Rothenberg:LOXO Oncology Inc.: Employment. Tsai:Eli Lilly and Company: Employment. Ku:Eli Lilly and Company: Employment. Wang:BioInvent: Consultancy, Research Funding; VelosBio: Research Funding; Loxo Oncology: Research Funding; Guidepoint Global: Consultancy; Kite Pharma: Consultancy, Research Funding; Pharmacyclics: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Acerta Pharma: Consultancy, Research Funding; MoreHealth: Consultancy, Equity Ownership; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; Juno Therapeutics: Research Funding; Dava Oncology: Honoraria; Aviara: Research Funding.

BackgroundIn SELECT-PsA 1, patients (pts) with psoriatic arthritis (PsA) and an inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug showed improvement in the signs and symptoms of PsA with upadacitinib 15 mg (UPA15) or 30 mg (UPA30), an oral Janus kinase (JAK) inhibitor, through week (wk) 56.1ObjectivesTo evaluate the efficacy and safety of UPA and UPA vs adalimumab (ADA) at wk 104 from the ongoing long-term extension of SELECT-PsA 1.MethodsPts received UPA15, UPA30, ADA 40 mg, or placebo (PBO) for 24 wks, at which point, PBO pts switched to UPA15 or UPA30. Efficacy endpoints were analyzed using non-responder imputation (NRI) and as observed (AO) (binary endpoints) or mixed-effect model repeated measures and AO (continuous endpoints), with nominal P-values shown, for continuous UPA and ADA treatment groups. Treatment-emergent adverse events were summarized for pts who received ≥1 dose of study drug using a visit-based cut-off at wk 104.Results1704 pts received ≥1 dose of study drug. At wk 104, 25.4% of patients had discontinued study drug. The proportions of pts who achieved ACR20/50/70, MDA, PASI75/90/100, and resolution of enthesitis or dactylitis showed consistent responses, or further improvements, from wk 561 to wk 104 (Table 1). ACR20/50/70 and MDA responses, as well as mean change from baseline (BL) in HAQ-DI, patient’s assessment of pain, BASDAI, and ASDAS, were greater with UPA vs ADA. Mean change from BL in modified total Sharp/van der Heijde Score (mTSS) was generally similar across groups and comparable to wk 56.1 The safety profile of UPA was generally comparable to ADA (Figure 1) and consistent with wk 561 data. Rates of serious infection, herpes zoster, lymphopenia, and elevated CPK remained numerically higher with UPA30 vs UPA15; rates in both UPA groups were higher vs ADA. Rates of malignancies, MACE, or VTE were similar across groups, and consistent with wk 561 data. Two deaths were reported with UPA15, 1 with UPA30, and 1 with ADA.Table 1.Efficacy Endpoints at Week 104EndpointUPA15(n=429)UPA30(n=423)ADA(n=429)Proportion of Pts (%)aNRIAONRIAONRIAOACR2069.087.969.587.963.485.1ACR5053.667.459.3*74.147.162.3ACR7038.0*47.443.5*54.429.439.1Minimal Disease Activity (MDA)42.054.845.9*56.837.850.3PASI75b57.973.462.478.658.876.5PASI90b46.759.053.366.548.863.3PASI100b34.143.442.451.434.144.0Resolution of enthesitis by LEIc53.375.552.272.049.173.9Resolution of dactylitis by LDId69.994.571.796.272.495.2Change from BLeMMRMAOMMRMAOMMRMAOHealth Assessment Questionnaire - Disability Index (HAQ-DI)-0.55*-0.57-0.55*-0.59-0.45-0.47Patient’s assessment of pain (numeric rating scale)-3.3-3.5-3.4*-3.6-3.0-3.2Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)f-3.0-3.2-3.3-3.6-2.7-2.6Ankylosing Spondylitis Disease Activity Score (ASDAS)f-1.6-1.8-1.9*-2.1-1.5-1.6Modified total Sharp/van der Heijde Score (mTSS)0.030.010.010.000.110.11ACR20/50/70, ≥20%/50%/70% improvement in American College of Rheumatology criteria; ADA, adalimumab; AO, as observed; BL, baseline; LDI, Leeds Dactylitis Index; LEI, Leeds Enthesitis Index; MMRM, mixed effect model repeated measurement; NRI, non-responder imputation; PASI75/90/100, ≥75%/90%/100% improvement in Psoriasis Area and Severity Index; pts, patients; UPA, upadacitinib.aData shown as NRI and AO for binary endpoints.bFor pts with psoriasis affecting ≥3% of body surface area at BL.cFor pts with LEI >0 at BL; resolution LEI=0.dFor pts with LDI >0 at BL; resolution LDI=0.eData shown as MMRM (LS mean) and AO (mean) for continuous endpoints.fFor pts with psoriatic spondylitis at BL.Nominal *P<0.05, UPA15 or UPA30 vs ADA for NRI and MMRM; AO descriptive only.ConclusionIn PsA pts, efficacy responses were similar or greater with UPA15 or UPA30 vs ADA at wk 104, and inhibition of radiographic progression was maintained. No new safety signals were identified with long-term exposure to UPA up to 2 years.References[1]McInnes I, et al. RMD Open, 2021; 7(3):e001838.AcknowledgementsAbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial (NCT03104400). AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Monica R.P. Elmore, PhD of AbbVie.Disclosure of InterestsIain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sanofi Regeneron, and UCB Pharma, Koji Kato Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Marina Magrey Consultant of: UCB, Novartis, Eli Lilly, Pfizer, and Janssen, Grant/research support from: Amgen, AbbVie, and UCB Pharma, Joseph F. Merola Consultant of: Merck, Bristol-Myers Squibb, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres, and Leo Pharma, Mitsumasa Kishimoto Consultant of: AbbVie, Amgen-Astellas BioPharma, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Celgene, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Kyowa Kirin, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, Teijin Pharma, and UCB Pharma, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, Consultant of: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli-Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi Genzyme, Takeda, UCB, Grant/research support from: AbbVie, Adiga Life-Sciences, Amgen, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Eli-Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, UCB, Liang Chen Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Yuanyuan Duan Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Jianzhong Liu Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Ralph Lippe Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie, Peter Wung Shareholder of: Employee of AbbVie and may hold stock or options, Employee of: Employee of AbbVie

Skills in biomedical ethics are limited in the African health care systems. This significantly affects the bioethics discourse in the medical practice. The main reason for the paucity in knowledge and skills in bioethics is minimal or no training at all imparted to healthcare professionals. Where there is training, it is not well-structured like other courses in the training institutions. This report summarizes the status of bioethics training and outlines the implementation, processes, outcome and future outlook of a bioethics teaching project for masters in medicine residents (students) in a tertiary referral hospital in Africa. This project was part of postgraduate studies in biomedical ethics by a practicing physician. It entailed teaching bioethics to first year master’s in medicine residents (students). The teachings occurred in the author’s affiliated institution monthly for six-months. The topics covered were: general introduction to bioethics, ethical issues at end-of-life (EoL), informed consent, basics of research ethics, plagiarism and doctor-pharma interaction. These topics were selected due to their relevance to the residents in their practice and because they needed to undertake research studies to graduate from the masters training program. In addition, these basic bioethics training provided the residents with the foundation to develop knowledge geared towards improving skills in analyzing diverse areas in the contemporary bioethics’ environment such as end-of-life care (EoLC), human research ethics, doctor-pharmaceutical relationships while looking at them within the context of political, cultural, socio-economic, and environmental determinants.

Introduction: CPX-351 (Vyxeos®; daunorubicin and cytarabine liposome for injection), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, has been approved by the US FDA and the EMA for the treatment of adults with newly diagnosed, therapy-related AML or AML with myelodysplasia-related changes. The primary analysis of the pivotal phase 3 study (NCT01696084) that formed the basis for these approvals evaluated patients aged 60 to 75 years with newly diagnosed high-risk/secondary AML and found that, with a median follow-up of 20.7 months, CPX-351 significantly improved median overall survival (OS) versus conventional 7+3, with a comparable safety profile. Final 5-year follow-up results recently reported demonstrated that the OS benefit was maintained. To evaluate both quality and quantity of life, we conducted a Q-TWiST analysis of the phase 3 study to compare survival between patients receiving CPX-351 versus 7+3. Methods: Q-TWiST is used to evaluate outcomes in oncology trials by measuring how much of the survival improvement time is spent with toxicities, how much after disease progression or relapse, and how much is valuable time (ie, Time Without Symptoms of Disease and Toxicity [TWiST]). For this analysis, the OS for each patient from the 5-year follow-up analysis was partitioned into 3 health states: TOX (time before response plus any additional time with a grade 3 or 4 toxicity), TWiST (time without relapse or grade 3 or 4 toxicity), and REL (time after relapse). Q-TWiST gain was assessed as the mean time spent in each state weighted by its respective quality of life, represented by health utility (U; scale of 0.0 [indicates death] to 1.0 [indicates "perfect" health]). Q-TWiST gain was calculated as follows: Q-TWiST = (UTWiST × TWiST) + (UTOX × TOX) + (UREL × REL). The base case scenario used the intent-to-treat population, any grade 3 or 4 toxicities, TOX and REL utility weights of 0.5, and a TWiST utility weight of 1.0. Sensitivity analyses were performed for all treated patients (CPX-351: n = 153; 7+3: n = 151) and the intent-to-treat population, any and treatment-related grade 3 or 4 toxicities, and TOX and REL utility weights of 0, 0.5, and 1.0. A variation of the base case scenario was also performed for the subset of patients who achieved complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CR+CRi; CPX-351: n = 73; 7+3: n = 52). When comparing across populations or studies, reporting relative Q-TWiST gains is an effective measure for evaluating clinical benefit (ie, Q-TWiST gains compared to a control; Solem CT, et al. Expert Rev Pharm Out 2018). A relative Q-TWiST gain of 15% or greater is considered a clinically important difference (CID) in oncology studies (Revicki DA, et al. Qual Life Res 2006). The relative Q-TWiST gain was calculated using the following equation: Q-TWiST difference ÷ mean OS of control arm × 100. Results: In total, 309 patients were randomized to CPX-351 (n = 153) or 7+3 (n = 156). In the base case scenario, the means difference (95% CI) for CPX-351 versus 7+3 was 183 days (60, 306) for the TWiST state, 7 days (−63, 78) for the TOX state, and 22 days (5, 38) for the REL states. The resulting means difference (95% CI) for Q-TWiST gain was 197 days (76, 319) for CPX-351 versus 7+3, and the relative Q-TWiST gain was 53.6%. Among patients who achieved CR or CRi, the means difference (95% CI) for Q-TWiST gain was 248 days (−1, 496) for CPX-351 versus 7+3, and the relative Q-TWiST gain was 39.8%. Both relative Q-TWiST gains were considerably above the standard CID of 15% for oncology. Across the various sensitivity analyses, the relative Q-TWiST gains for CPX-351 versus 7+3 varied from 48.0% to 57.6%, remaining all well above the standard CID threshold (Table). Conclusions: Results of this post hoc analysis suggest the survival benefit with CPX-351 for patients with high-risk/secondary AML are mostly from valuable time (TWiST), thus supporting the clinical benefit for patients. The relative Q-TWiST gains were well above what is considered CID (15%) in the cancer literature and were maintained across various sensitivity analyses, supporting the robustness of the benefit. In the absence of direct measures of quality of life, these results can be used together with the antileukemia effect when considering treatment options for this patient population. Disclosures Cortes: Daiichi Sankyo: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Sun Pharma: Research Funding; Pfizer: Consultancy, Research Funding; BioPath Holdings: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Telios: Research Funding; Astellas: Research Funding; Amphivena Therapeutics: Research Funding; Arog: Research Funding; BiolineRx: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Merus: Research Funding; Immunogen: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Lin:Aptevo: Research Funding; Abbvie: Research Funding; Gilead Sciences: Research Funding; Genetech-Roche: Research Funding; Incyte: Research Funding; Celyad: Research Funding; Celgene: Research Funding; Jazz: Research Funding; Mateon Therapeutics: Research Funding; Ono Pharmaceutical: Research Funding; Bio-Path Holdings: Research Funding; Astellas Pharma: Research Funding; Prescient Therapeutics: Research Funding; Pfizer: Research Funding; Trovagene: Research Funding; Tolero Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding. Uy:Daiichi Sankyo: Consultancy; Pfizer: Consultancy; Agios: Consultancy; Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Astellas Pharma: Honoraria. Ryan:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Faderl:Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Lancet:Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy.

Mounting evidence indicates that worldwide, innovation systems are increasing unsustainable. Equally, concerns about inequities in the science and innovation process, and in access to its benefits, continue. Against a backdrop of growing health, economic and scientific challenges global stakeholders are urgently seeking to spur innovation and maximize the just distribution of benefits for all. Open Science collaboration (OS) – comprising a variety of approaches to increase open, public, and rapid mobilization of scientific knowledge – is seen to be one of the most promising ways forward. Yet, many decision-makers hesitate to construct policy to support the adoption and implementation of OS without access to substantive, clear and reliable evidence. In October 2017, international thought-leaders gathered at an Open Science Leadership Forum in the Washington DC offices of the Bill and Melinda Gates Foundation to share their views on what successful Open Science looks like. Delegates from developed and developing nations, national governments, science agencies and funding bodies, philanthropy, researchers, patient organizations and the biotechnology, pharma and artificial intelligence (AI) industries discussed the outcomes that would rally them to invest in OS, as well as wider issues of policy and implementation. This first of two reports, summarizes delegates' views on what they believe OS will deliver in terms of research, innovation and social impact in the life sciences. Through open and collaborative process over the next months, we will translate these success outcomes into a toolkit of quantitative and qualitative indicators to assess when, where and how open science collaborations best advance research, innovation and social benefit. Ultimately, this work aims to develop and openly share tools to allow stakeholders to evaluate and re-invent their innovation ecosystems, to maximize value for the global public and patients, and address long-standing questions about the mechanics of innovation.

Mounting evidence indicates that worldwide, innovation systems are increasing unsustainable. Equally, concerns about inequities in the science and innovation process, and in access to its benefits, continue. Against a backdrop of growing health, economic and scientific challenges global stakeholders are urgently seeking to spur innovation and maximize the just distribution of benefits for all. Open Science collaboration (OS) – comprising a variety of approaches to increase open, public, and rapid mobilization of scientific knowledge – is seen to be one of the most promising ways forward. Yet, many decision-makers hesitate to construct policy to support the adoption and implementation of OS without access to substantive, clear and reliable evidence. In October 2017, international thought-leaders gathered at an Open Science Leadership Forum in the Washington DC offices of the Bill and Melinda Gates Foundation to share their views on what successful Open Science looks like. Delegates from developed and developing nations, national governments, science agencies and funding bodies, philanthropy, researchers, patient organizations and the biotechnology, pharma and artificial intelligence (AI) industries discussed the outcomes that would rally them to invest in OS, as well as wider issues of policy and implementation. This first of two reports, summarizes delegates' views on what they believe OS will deliver in terms of research, innovation and social impact in the life sciences. Through open and collaborative process over the next months, we will translate these success outcomes into a toolkit of quantitative and qualitative indicators to assess when, where and how open science collaborations best advance research, innovation and social benefit. Ultimately, this work aims to develop and openly share tools to allow stakeholders to evaluate and re-invent their innovation ecosystems, to maximize value for the global public and patients, and address long-standing questions about the mechanics of innovation.

Background:The recent prospectively validated definition of the lupus low disease activity state (LLDAS) allows characterisation of patients not achieving a treatment goal, providing impetus for an analysis of unmet needs in SLE using formal definitions. Other recently described definitions of high disease burden include disease activity over time, high disease activity status (HDAS) episodes, and the combination of high disease activity, serological activity and glucocorticoid (GC) use (HDAS+SA+GC).Objectives:To determine the prevalence of formal categories of unmet need, and the association of these with adverse outcomes, in SLE.Methods:Data from a 13-country longitudinal SLE cohort (ACR/SLICC criteria) were collected between 2013 and 19 using standard templates. Unmet need was defined as (i) patients never attaining LLDAS defined as in Golder et al., 2019 [1], (ii) having persistently active disease (time adjusted mean SLEDAI-2K (AMS) > 4), (iii) ever exhibiting high disease activity status (HDAS; SLEDAI-2K ≥10[2]), or (iv) ever exhibiting all of SLEDAI≥10, serological activity, and glucocorticoid use (HDAS+SA+GC)[3]. Health-related quality of life (HRQoL) was assessed using SF36 (v2) surveys and damage accrual using SLE Damage Index (SDI).Results:3,384 SLE patients were followed for 30,313 visits over median [IQR] 2.4 [0.4, 4.3] years. 53% of all visits were not in LLDAS; 813 patients (24%) never achieved LLDAS during observation. Median AMS was 3.0 [1.4, 4.9] and 34% of patients had AMS > 4 throughout the study. 25% of patients had at least one episode of HDAS, representing 8% of visits. 702 patients (21%) had at least one episode of HDAS+SA+GC, representing 8% of visits. Each of never-LLDAS, AMS>4, ever-HDAS, and ever-HDAS+SA+GC were associated with significantly greater number of physician visits, higher mean glucocorticoid dose, lower HRQoL and higher mortality. 31%, 58% and 83% of never-LLDAS, AMS>4, and ever-HDAS patients respectively were also HDAS+SA+GC on at least one occasion.Conclusion:Data from a multinational longitudinal SLE cohort indicate that unmet need, defined by LLDAS-never, AMS>4, HDAS, or HDAS+SA+GC, is prevalent in SLE, and that these definitions are associated with poor outcomes.References:[1]Golder, V., et al., Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology, 2019. 1(2): p. e95-e102.[2]Koelmeyer, R., et al., High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus. Lupus Sci Med, 2020. 7(1).[3]van Vollenhoven, R.F., et al., Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Annals of the Rheumatic Diseases, 2012. 71(8): p. 1343-1349.Acknowledgements:The APLC acknowledges all the Data Collectors and Patients for their valuable contributions to research.Disclosure of Interests:Rangi Kandane-Rathnayake: None declared, Worawit Louthrenoo: None declared, Alberta Hoi Consultant of: Abbvie and GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Vera Golder: None declared, Yi-Hsing Chen Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Consultant of: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead, Grant/research support from: Pfizer, Norvatis, BMS, Abbevie, Johnson & Johnson, Roche, Sanofi, Guigai, Roche, Boehringer Ingelheim, UCB, MSD, Astra-Zeneca, Astellas, Gilead, Shue Fen Luo: None declared, Yeong-Jian Jan Wu Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, Aisha Lateef: None declared, Jiacai Cho: None declared, Laniyati Hamijoyo Speakers bureau: Pfizer, Novartis, Abbot, Chak Sing Lau Shareholder of: Pfizer, Sanofi, and Janssen, Sandra Navarra Speakers bureau: Pfizer, Johnson & Johnson, Novartis, Astellas, Grant/research support from: Astellas, Johnson & Johnson, Leonid Zamora: None declared, Zhanguo Li Speakers bureau: Eli, Lilly, Novartis, GSK, AbbVie, Paid instructor for: Pfizer, Roche, Johnson., Consultant of: Lilly, Pfizer, Grant/research support from: Pfizer, Yuan An: None declared, Sargunan Sockalingam Speakers bureau: Pfizer, Roche, Novartis, Grant/research support from: Roche and Novartis, Yasuhiro Katsumata Speakers bureau: Chugai Pharmaceutical Co., Ltd., Glaxo-Smithkline K.K., and Sanofi K.K., masayoshi harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang Speakers bureau: Norvatis, GSK, Pfizer, Jun Kikuchi: None declared, Tsutomu Takeuchi Speakers bureau: AbbVie AYUMI Pharmaceutical Corp. Bristol-Myers Squibb Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan, Gilead Sciences, Inc. Mitsubishi-Tanabe Pharma Corp. Pfizer Japan Inc. Sanofi K.K., Consultant of: Astellas Pharma, Inc. Chugai Pharmaceutical Co, Ltd. Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Grant/research support from: AbbVie, Asahikasei Pharma Corp. Chugai Pharmaceutical Co, Ltd. Mitsubishi-Tanabe Pharma Corp. Sanofi K.K., BMDB Basnayake: None declared, Fiona Goldblatt: None declared, Madelynn Chan Speakers bureau: AbbVie, Novartis, Consultant of: Pfizer, Eli-Lilly, Kristine Ng Speakers bureau: Abbvie, Novartis, Janssen, Sang-Cheol Bae: None declared, Shereen Oon: None declared, Sean O’Neill Consultant of: GSK, Kathryn Gibson Speakers bureau: UCB, Consultant of: Novartis, Janssen, Grant/research support from: Novartis, Sunil Kumar: None declared, Nicola Tugnet: None declared, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, Grant/research support from: Abbvie, Mitsubishi-Tanabe, Chugai, Asahi-Kasei, Eisai, Takeda, Daiichi-Sankyo, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Eric F. Morand Speakers bureau: AstraZeneca, Paid instructor for: Eli Lilly, Consultant of: AstraZeneca, Amgen, Biogen, BristolMyersSquibb, Eli Lilly, EMD Serono, Genentech, Janssen, Grant/research support from: AstraZeneca, BristolMyersSquibb, Eli Lilly, EMD Serono, Janssen.