Journal articles on the topic 'Jan Lauwers'

Background:Induced arthritis (IA) is a rare immune related adverse event occurring in 0.5 to 2% of patients exposed to Immune (irAEs) Checkpoint Inhibitors (CPI). In some patients, this condition may be severe and long lasting even after CPI cessation. Cross-reactivity between tumor- and self-antigens was considered in the etiology of several cases of irAEs but disease mechanisms in IA remain elusive.We systematically collect synovial tissue of patients with IA (Ethical Committee B403201942386).Objectives:Here, we report the histopathological findings from ultrasound guided (USG) synovial biopsies from the 3 first patients of our cohort. The immune cell infiltration in CPI IA patients is compared to the histopathological findings in rheumatoid arthritis.Methods:Patients were referred through their oncologist after the onset of an arthritis in the context of a CPI therapy. The diagnostic of arthritis was confirmed by a rheumatologist and by ultrasound assessment. USG biopsies were performed before initiation of specific therapies.Pathological and immunohistochemical analyses include semi quantitative scoring of the following: synovial hyperplasia, fibrinoid necrosis, chorion cellular infiltrate, vascular hyperplasia, CD3-, CD20-, CD68- and CD138-positive cells.All patients gave written informed consent.Results:Three patients went through the USG biopsy procedure: 2 males and 1 female. No adverse events were recorded.All patients had metastatic neoplasms and time-to-arthritis was on average 6.7 months after CPI initiation. The USG biopsies were performed from 1 week after the onset of the IA to 16 months. The target joints displayed strong synovial thickening on ultrasound. Histological and immunohistochemistry studies showed light to moderate synovial hyperplasia and inflammatory cell infiltration of the sublining by macrophages and T cells, but no or little B cells (Table 1).Table 1.Clinical Characteristics and histopathological analyses on synovial biopsies.Patient 1Patient 2Patient 3CanceruterusbladderlungsBiopsied jointfirst metatarsophalangial jointwristkneeTime-to-synovial biopsy1 week2 months16 monthsGrey scale on ultrasound3/33/33/3Hematoxylin-eosin staining:synovial hyperplasiafibrinoid necrosischorion cellular infiltratevascular hyperplasia++++0+++++++00/+++Immunochemistry staining:CD3CD20CD68CD138++++000/+++0/+++000/+Conclusion:USG synovial biopsies have been safely performed and the histopathological analysis have confirmed the synovitis with mainly a macrophage infiltrate (myeloid pattern). IA synovitis is characterized by synovial hyperplasia and macrophage and T cell infiltration of the sublining. Increased collaboration between oncologists and rheumatologists is needed to create opportunities for referral of patients between the two specialties and optimize treatment. Further analyses (such as global or single-cell RNA sequencing) are needed to learn more about IA physiopathology.References:[1]Humby F, Lewis M, Ramamoorthi N & al. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Ann Rheum Dis. 2019 Jun;78(6):761-772. doi: 10.1136/annrheumdis-2018-214539.[2]Postow MA, Sidlow R, Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018 Jan 11;378(2):158-168. doi: 10.1056/NEJMra1703481. PMID: 29320654.Disclosure of Interests:Meric de Bellefon Laurent: None declared, Aspeslagh Sandrone: None declared, Di Romana Silvana: None declared, Cornelis Frank: None declared, Poncin Renaud: None declared, Christine Galant: None declared, Bernard Lauwerys Employee of: Bernard Lauwerys is currently employed at UCB Biopharma, Patrick Durez: None declared

Background:The Tool for Administrative Reimbursement Drug Information Sharing (TARDIS) is an electronic platform combining data collection from all Belgian patients with Rheumatoid Arthritis (RA) on advanced therapy, together with a drug reimbursement request. Therapy choice after initial 2 classical synthetic DMARD failure is left to the treating rheumatologist in Belgium.Objectives:To investigate first-line therapy choices for tumor necrosis factor inhibitor (TNFi) biologic (b) DMARDs, non-TNFi bDMARDs or targeted synthetic (ts) DMARDs via patient characteristics and initial treatment response in the TARDIS-RA registry.Methods:All Belgian rheumatologist inserted patient data online when prescribing a b/tsDMARD. When data was entered for the first time, previous and current use of DMARD therapies was registered. Every next bDMARD or tsDMARD initiation, prolongation and discontinuation was registered electronically. First prolongation is 6 months for bDMARDs and 12 weeks for tsDMARDs, and yearly thereafter. Patients were selected for this analysis if they started a TNFi, non-TNFi or tsDMARD therapy between Jan 2018 and Jan 2019. Rituximab was excluded. Baseline characteristics of bionaive patients per therapy were compared with Mann-Whitney U or Chi2tests were appropriate. Regression analyses, adjusted for age, DAS28 baseline and disease duration, evaluated DAS28 change, remission (DAS28<2.6) and low disease activity (LDA, DAS28<3.2) between b/tsDMARDs at first TARDIS follow-up.Results:In 2018, 1263 bionaive RA patients were included. Table 1 describes this population. Time until 1stfollow-up differed between groups with 183 (181-184) days for bDMARD versus 84 (84-84) days for tsDMARD patients. Lineair regression showed an effect of therapy type on DAS28 change in bionaive patients (p=0.017). Logistic regression showed no difference per therapy for remission (p=0.090) nor low disease activity (p=0.123). Proportions of therapy prolongations at 1stfollow up visit did not differ per therapy type.Table 1.Baseline characteristics and treatment response of first-line TNFi, Non-TNFi or tsDMARDsTNFiNon-TNFitsDMARDp-valueNumber patients696 (57%)293 (25%)215 (18%)Age (years)55, (45-64)58, (51-68)58, (49-66)<0.001Disease duration (years)3, (1-7)3, (1-9)5, (2-13)<0.001DAS28 Baseline4.8, (4.3-5.5)5.1, (4.4-5.7)4.7, (4.2-5.4)0.010DAS28 Change2.2 (1.0-3.0)2.2 (1.1-3.2)1.9 (0.9-2.7)0.014Remission296 (50%)123 (49%)78 (42%)0.143LDA377 (64%)153 (61%)105 (56%)0.196Prolongation therapy492 (82%)219 (87%)161 (86%)0.158Number given are median, (IQR) or number (proportion). TNFi = tumour necrosis factor inhibitor, ts= targeted synthetic, DAS = disease activity score, DAS28 change = DAS28 at 1st follow up visit minus DAS28 at baseline, remission = DAS28<2.6), LDA = low disease activity = DAS28<3.2), Prolongation = therapy was continued at 1st follow-up visit. Mann-Whitney U or Chi square tests were used where appropriate.Conclusion:Initial therapy choices are partially driven by patient profile, although other factors such as patient preferences could not be verified. DAS28 change for tsDMARDs seemed less important versus bDMARDs, but can possibly be attributed to the preset evaluation moment being sooner for tsDMARDs versus bDMARDs aside of patient profile differences in age and disease duration. In contrast, proportion of remission, low disease activity and therapy prolongation did not differ by therapy.Disclosure of Interests:Diederik De Cock: None declared, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Dirk Elewaut: None declared, Bernard Lauwerys: None declared, Rene Westhovens Grant/research support from: Celltrion Inc, Galapagos, Gilead, Consultant of: Celltrion Inc, Galapagos, Gilead, Speakers bureau: Celltrion Inc, Galapagos, Gilead, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies

Background:Modes of action of DMARDs (disease-modifying antirheumatic drugs) in rheumatoid arthritis (RA) are not completely understood at the level of the synovium. Studying treatment-induced modifications in RA synovial tissue can provide unique insights into the pathways modulated downstream of different DMARDs.Objectives:Our goal was to assess histological and transcriptomic effects of Abatacept (ABA) on RA synovium, and to compare them with previously published data obtained by our group using the same study design on other DMARDs: Tocilizumab (TCZ), Rituximab (RTX), Methotrexate (MTX) and Adalimumab (ADA).Methods:Synovial tissue was obtained using ultrasound-guided biopsy from affected joints before (W0) and 16 weeks (W16) after treatment with subcutaneous Abatacept 125mg per week on a MTX background. Paraffin-sections were stained for CD3, CD20 and CD68 and scored by a pathologist for T cell, B cell and macrophage infiltration. Transcriptional profiling was performed using GeneChip Human Genome U133 Plus 2.0 arrays (Affymetrix), and analyzed on Genespring GX (Agilent). Pathway analyses were performed on Genespring GX, Metascape (https://metascape.org/) and EnrichR (https://maayanlab.cloud/Enrichr/). Protein-Protein Interaction (PPI) networks were generated on STRING (https://string-db.org/).Results:14 RA patients were included (female: 9, ACPA/RF positive: 8, erosive disease: 12, median disease duration in years (± SD): 11.7 (± 8.1), median DAS28CRP (± SD): 4.78 (± 1.11)). Median DAS28CRP significantly decreased between W0 and W16, as did US GS score. Evaluation of histological slides (n=11 pairs of samples) showed no significant effect of Abatacept on T cell, B cell or macrophage infiltration. Gene expression analysis (n=10 pairs of samples) identified 304 transcripts differentially expressed (129 downregulated, 175 upregulated) between W0 and W16 (FC≥1.5 and p<0.05, paired Mann-Whitney). Downregulated genes were significantly enriched for immune processes and included several key T cell regulatory genes (IL2RA, CD28, IL7, IL7R), strongly overlapping with data from previous studies on TCZ (n= 12 pairs), RTX (n=12 pairs), MTX (n=8 pairs) and ADA (n=8 pairs). Thus, each treatment shares 31 to 48% of its downregulated genes with the others, with genes downregulated by at least three involved in key RA-associated pathways such as leukocyte activation, NF-kappa B signaling, TNF signaling and JAK-STAT signaling. Given their seemingly overlapping effects, data were pooled across these studies, markedly improving power thanks to their paired-design. This revealed that genes downregulated by DMARDs (n=573, Benjamini-Hochberg corrected p-value<0.05, paired Mann-Whitney) were significantly enriched for both T cell and myeloid leukocyte activation pathways. Interestingly, DMARDs seem to have a coordinate effect on the two pathways (correlation of mean Log2FC: r=0.8558, p<0.0001), with a stronger impact (Log2FCW16-W0) in good responders to therapy (n=17) as compared to moderate (n=20) and to non-responders (n=13) (p<0.0001, Mann-Whitney). Finally, Transcription Factor enrichment and PPI network analyses point to a central role for molecules including JAK/STATs as mediators of all studied therapies.Conclusion:We provide evidence that the effects of five DMARDs on RA synovium culminate in the same pathways (namely, T cell and myeloid leukocyte activation). This confirms previous studies suggesting the existence of common mediators downstream of DMARDs, independent of their primary targets, and suggests attractive new therapeutic targets.Acknowledgements:This work was funded in part by unrestricted grants from Cap48 (RTBF) and Bristol-Myers Squibb. Clément Triaille is funded by the Fonds National de la Recherche Scientifique (FNRS, Communauté française de Belgique) and Fondation Saint-Luc (Cliniques Universitaires Saint-Luc).Disclosure of Interests:Clément Triaille: None declared, Tilman Gaelle: None declared, Tatiana Sokolova: None declared, Laurent Meric de Bellefon: None declared, Christine Galant: None declared, Patrick Durez Grant/research support from: unrestricted research grant from Bristol-Myers Squibb, Bernard Lauwerys Employee of: currently employed at UCB Biopharma, Nisha Limaye: None declared

Topic of the essay is the so called "Identity Politics", which is currently discussed with regard to theatre and the visual arts at numerous places: Who is allowed to represent whom on stage and in the arts in general? And how to deal with the alterity of the other on stage? Activists accuse white artists to appropriate black suffering and to instrumentalise it in order to sell their works. (Hannah Black vs. Dana Schutz) Theatre directors are critizised for their unreflected use of blackface on stage. (Bühnenwatch vs. Didi Hallervorden, Sebastian Baumgarten) Performance groups which bring people of colour or disabled performers on stage are accused of exploitation or paternalism. (Monster Truck, Jerome Bel) Amongst the topics of the discussion there was one of the most important ones how the traditional white European theatre deals structurally with minorities being underrepresented on stage because of their skin colour, their disability or their sexual orientation. Against the backdrop of these debates I would like to argue in my lecture that theatre’s contribution to the debate on identity and diversity lies in its questioning of the very logic of identity as such. Departing from Jan Lauwers‘ production Blind poet and perhaps some other examples I will try to show that this production shows to what extent any positing of identity is based on the construction of a phantasm. Identity is the result of the drawing of a border which establishes a binary opposition between the foreign other outside of us and our self opposed to it. Theatre questions these borders by confronting us with the foreign other within ourselves, with an originary de-position of the origins our identitys are based on.

Topic of the essay is the so called "Identity Politics", which is currently discussed with regard to theatre and the visual arts at numerous places: Who is allowed to represent whom on stage and in the arts in general? And how to deal with the alterity of the other on stage? Activists accuse white artists to appropriate black suffering and to instrumentalise it in order to sell their works. (Hannah Black vs. Dana Schutz) Theatre directors are critizised for their unreflected use of blackface on stage. (Bühnenwatch vs. Didi Hallervorden, Sebastian Baumgarten) Performance groups which bring people of colour or disabled performers on stage are accused of exploitation or paternalism. (Monster Truck, Jerome Bel) Amongst the topics of the discussion there was one of the most important ones how the traditional white European theatre deals structurally with minorities being underrepresented on stage because of their skin colour, their disability or their sexual orientation. Against the backdrop of these debates I would like to argue in my lecture that theatre’s contribution to the debate on identity and diversity lies in its questioning of the very logic of identity as such. Departing from Jan Lauwers‘ production Blind poet and perhaps some other examples I will try to show that this production shows to what extent any positing of identity is based on the construction of a phantasm. Identity is the result of the drawing of a border which establishes a binary opposition between the foreign other outside of us and our self opposed to it. Theatre questions these borders by confronting us with the foreign other within ourselves, with an originary de-position of the origins our identitys are based on.