Книги: "Target therapies"

1

Dzau, Victor J., and Gabor M. Rubanyi. The endothelium in clinical practice: Source and target of novel therapies. New York: M. Dekker, 1997.

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2

Albert, Jeffrey S., and Michael W. Wood. Targets and emerging therapies for schizophrenia. Hoboken (New Jersey), USA: John Wiley & Sons, 2012.

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3

Albert, Jeffrey S., and Michael W. Wood, eds. Targets and Emerging Therapies for Schizophrenia. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2012. http://dx.doi.org/10.1002/9781118309421.

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4

Los, Marek, and Spencer B. Gibson, eds. Apoptotic Pathways as Targets for Novel Therapies in Cancer and Other Diseases. New York: Springer-Verlag, 2005. http://dx.doi.org/10.1007/b102187.

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5

H, Herfarth, ed. Targets of treatment in chronic inflammatory bowel diseases: Proceedings of Falk Symposium 131 (part II of the Gastroenterology Week, Freiburg, Germany, October 6-8, 2002). Dordrecht: Kluwer Academic, 2003.

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6

Hillis, Argye E., and Jean-Claude Baron, eds. The Ischemic Penumbra: Still the Target for Stroke Therapies? Frontiers Media SA, 2015. http://dx.doi.org/10.3389/978-2-88919-635-7.

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7

Corporation, Market Intelligence Research, and Frost & Sullivan., eds. Autoimmune disease: Therapeutic markets : new therapies target causes, not symptoms. Mountain View, CA: Market Intelligence, 1992.

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8

Drouin-Ouellet, Janelle, and Roger A. Barker. Disease-Modifying Therapies in Neurodegenerative Disorders. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190233563.003.0016.

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The recent identification of the genetic basis of many neurodegenerative disorders (NDDs), coupled with a greater understanding of their pathophysiology, has enabled better therapeutic strategies to be identified and tried. This includes approaches that target critical specific nodes in the disease pathways, for example, agents that modulate levels of mutant huntingtin in Huntington’s disease. In addition to these highly specific targeted therapies, there is also a growing realization that more generic lifestyle therapies influencing whole brain health may also have merit in treating these conditions-such as diet and exercise. This chapter explores the different approaches and agents used to try to modify the course of a range of NDDs, and highlights their progress relative to the clinic and the patients suffering with these currently incurable conditions.

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9

Freeman, Charlene. Oral Medication and Insulin Therapies: A Practical Guide for Reaching Diabetes Target Goals. PESI HealthCare, 2003.

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10

Freeman, Charlene. Diabetes : A Practical Guide for Reaching Diabetes Target Goals: Oral Medication and Insulin Therapies. PESI, 2013.

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11

Masino, PHD, Susan A., ed. Ketogenic Diet and Metabolic Therapies. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190497996.001.0001.

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Ketogenic diets have been used to treat epilepsy for nearly a century. Alongside enduring clinical success with a ketogenic diet, metabolism’s critical role in health and in diseases in the central nervous system and throughout the body is increasingly appreciated. Furthermore, metabolism-based strategies have been proven equal or even superior to pharmacological treatments in specific cases and for specific diseases. Rather than causing unwanted off-target pharmacological side effects, addressing metabolic dysfunction can improve overall health simultaneously. Enduring interest in the ketogenic diet’s proven efficacy in stopping seizures and emerging efficacy in other disorders has fueled renewed efforts to determine key mechanisms and diverse applications of metabolic therapies. In parallel, multiple strategies are being developed to mobilize similar metabolic benefits without reliance on such a strict diet. Research interest in metabolic therapies has spread into laboratories and clinics of every discipline, and could yield entirely new classes of drugs and treatment regimens. This work is the first comprehensive scientific resource on the ketogenic diet, covering the latest research into the mechanisms, established and emerging applications, metabolic alternatives, and implications for health and disease. Experts in clinical and basic research share their research into mechanisms spanning from ion channels to epigenetics, their insights based on decades of experience with the ketogenic diet in epilepsy, and their evidence for emerging applications ranging from autism to Alzheimer’s disease to brain cancer.

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12

Mouyis, Maria, and David Isenberg. Biologic therapies in systemic lupus erythematosus. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198739180.003.0007.

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This chapter looks at the various biologic or target therapies that have been trialled and tested in the last two decades. The treatment of systemic lupus erythematosus (SLE) has progressed over the last few years due to an increased understanding of its pathogenesis; beginning with rituximab, one of the first biologics to be used, the chapter covers therapies up to the present day. Each subsection highlights the relevant mechanism of action which has led to new treatment options: anti-CD20 and 22, anti-B cell activating factors, anti-interferon alpha and anti-T cell activation. A summarized table is available providing a concise summary of the latest biologic therapies in treating SLE. The role of biologic therapies as monotherapy is still being defined, and with time there will be further change in the treatments available and the approach to the treatment of SLE using biologic therapies.

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13

Rubanyi, Gabor. Endothelium in Clinical Practice: Source & Target of Novel Therapies (Fundamental and Clinical Cardiology Series , No 29). Informa Healthcare, 1997.

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14

Cummings, Jeffrey L., and Kate Zhong. Clinical Trials and Drug Development in Neurodegenerative Diseases. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190233563.003.0018.

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This chapter describes the common therapeutic targets, approaches to clinical trial design, biomarkers, and therapeutic interventions across neurodegenerative disorders (NDDs). Each unique NDD-Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), etc.-has a unique phenotype associated with the regional cell population most affected. Each disease, however, is associated with protein misfolding, oxidation, inflammation, apoptosis, and cell death. If vulnerable cell populations include transmitter source nuclei, transmitter deficits also emerge (e.g. cholinergic abnormalities in AD and dopaminergic deficits in PD). Biomarkers show regionally appropriate brain atrophy or process-related cerebrospinal deficits. Clinical trial designs share features for symptomatic interventions (e.g. cholinesterase inhibitors in AD and dopamine agents in PD) and disease-modifying therapies. Biomarkers play similar roles in trials for NDD, including demonstrating target engagement and supporting disease modification. No disease-modifying therapies have been approved for any NDDs; all programs face similar pharmacokinetic, pharmacodynamic, and regulatory challenges in therapeutic development.

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15

Patel, Mayur B., and Pratik P. Pandharipande. Analgesics in critical illness. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0043.

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Analgesia is a critical component of intensive care unit (ICU) care. Accordingly, understanding the mechanism, physiological consequences, and assessment of pain is important when caring for the ICU patient. Non-pharmacological approaches should be attempted before supplementing analgesia with pharmacological agents. Pharmacologically-based therapies are divided into regional and systemic therapies. Regional analgesic therapies target specific areas of the body while limiting the systemic effects of intravenous analgesics, but at the risk of invasiveness, local anaesthetic toxicity, and infection of in-dwelling catheters. Systemic analgesic therapy is comprised of two main categories—non-opioids and opioids. Typically, non-opioid analgesics are used as adjunctive therapies and consist of agents such as non-steroidal anti-inflammatory drugs, gabapentinoids, ketamine, or α‎2 agonists. Opioid analgesia in the ICU is commonly infusion-based using fentanyl, hydromorphone, morphine, or recently, remifentanil.

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16

Wenham, Claire Y. J., and Philip G. Conaghan. Osteoarthritis—management. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0140.

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Osteoarthritis (OA) is a common condition which often causes pain and functional limitation, significantly impacting on a person's quality of life. A comprehensive assessment of the impact of OA should be performed before selecting therapies and treatment goals. Current recommended therapies include a combination of pharmacological and non-pharmacological therapies, which should be considered for all people with OA, regardless of anatomical site of involvement. Non-pharmacological treatments include education, muscle strengthening and aerobic exercises, weight loss if appropriate, splints and devices, and aids. Pharmacological therapies include paracetamol, oral and topical non-steroidal anti-inflammatory drugs, topical capsaicin, intra-articular corticosteroid injections, and opioids. Many existing therapies have only a small analgesic effect size and, in the case of drug therapies, may be associated with important side effects, so an individual's symptoms and comorbidities must be taken into account when selecting therapies. For those who do not respond to these treatments, surgery such as a total joint arthroplasty may be required. There is a strong need for new analgesic treatments for OA. As it is becoming increasingly clear that the sources of pain in OA are complex and multifactorial, future treatments for OA will need to target both peripheral and central pain mechanisms.

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17

Albert, Jeffrey S., and Michael W. Wood. Targets and Emerging Therapies for Schizophrenia. Wiley & Sons, Incorporated, John, 2012.

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18

Albert, Jeffrey S., and Michael W. Wood. Targets and Emerging Therapies for Schizophrenia. Wiley & Sons, Incorporated, John, 2012.

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19

Albert, Jeffrey S., and Michael W. Wood. Targets and Emerging Therapies for Schizophrenia. Wiley & Sons, Limited, John, 2012.

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20

Albert, Jeffrey S., and Michael W. Wood. Targets and Emerging Therapies for Schizophrenia. Wiley & Sons, Incorporated, John, 2012.

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21

Albert, Jeffrey S., and Michael W. Wood. Targets and Emerging Therapies for Schizophrenia. Wiley & Sons, Incorporated, John, 2012.

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22

Dryden, Matthew. Near-patient testing, infection biomarkers, and rapid diagnostics. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198758792.003.0017.

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Treating patients with targeted antimicrobial therapy is the gold standard of care. However, empiric antimicrobial guidelines are in operation for many patients in primary or secondary care with infection. These guidelines are based on previous surveillance data and/or national recommendations, but the decision to start treatment and the choice of antimicrobial is a best-guess approach, based on clinical judgement. Microbiology laboratory results help guide and target therapies, but in general they take about 1 to 2 days to be available due to the processes involved in culturing organisms. Improvement in speed of diagnosis is the focus of research, particularly around molecular diagnostics. Near-patient testing and the use of biomarkers has been discussed as a way to tackle this issue. This chapter also considers the alternatives and future strategies that could be deployed to improve the targeted therapy of antimicrobials.

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23

Walters, Jenna L. Complex Regional Pain Syndrome. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190217518.003.0025.

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Complex regional pain syndrome (CRPS) is a neuropathic pain condition classified as type 1 and type 2. The two classifications are distinguished by the presence of documented nerve injury in CRPS type 2. The symptoms of CRPS, including cold, blue, and painful extremities, are believed to occur from vasoconstriction caused by sympathetic dysfunction. Treatment in CRPS focuses on targeting neuropathic and sympathetically maintained pain. Traditional antineuropathic pain medications include membrane stabilizers and serotonin and norepinephrine reuptake inhibitors. Corticosteroids and nonsteroidals target the inflammatory process present in the initial stages of CRPS. Bone resorption has been treated with calcium-modulating drugs. Interventional therapies include sympathetic blockade of the affected extremity, spinal cord stimulation, and intrathecal drug delivery. All these therapies have been implemented in an effort to facilitate functional restoration of the affected limb. Physical and occupational therapies have demonstrated some of the most significant improvements in pain, mobility, and function.

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24

Klingenberg, Roland, and Ulf Müller-Ladner. Mechanisms of inflammation. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198784906.003.0270.

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This chapter provides a brief summary of the immune pathogenesis of atherosclerosis, highlighting shared features with inflammatory pathways in rheumatoid arthritis (RA) described in detail in Chapter 25.4. RA constitutes a prototype autoimmune disease primarily affecting the joints but also the heart and vessels associated with increased cardiovascular mortality. Recent years have produced a wealth of novel insights into the diversity of immune cell types which either propagate or dampen inflammation in atherogenesis. Expansion of this inherent anti-inflammatory component carried by regulatory T cells may constitute a new therapeutic target to harness the progression of atherosclerotic cardiovascular disease. Among the various inflammatory mediators involved in RA pathology, cytokines (tumour necrosis factor-α‎ and interleukin-6) have gained major interest as therapeutic targets with approved therapies available. In light of the many common features in the pathogenesis of RA and atherosclerosis, these biologics are currently being evaluated in cardiovascular patients. The recently published CANTOS trial showed that IL-1 inhibition reduced adverse cardiovascular events in patients with coronary artery disease demonstrating that inflammation is a genuine therapeutic target. The near future will provide more information whether inflammation is a bona fide cardiovascular risk factor based on completion of several clinical trials using anti-inflammatory approaches in patients with both cardiovascular disease and rheumatoid arthritis.

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25

Grunwald, Peter. Pharmaceutical Biocatalysis: Important Enzymes, Novel Targets, and Therapies. Jenny Stanford Publishing, 2020.

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26

Grunwald, Peter. Pharmaceutical Biocatalysis: Important Enzymes, Novel Targets, and Therapies. Jenny Stanford Publishing, 2020.

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27

Pharmaceutical Biocatalysis: Important Enzymes, Novel Targets, and Therapies. Jenny Stanford Publishing, 2020.

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28

Grunwald, Peter. Pharmaceutical Biocatalysis: Important Enzymes, Novel Targets, and Therapies. Jenny Stanford Publishing, 2020.

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29

Tennankore, Karthik K., and Christopher T. Chan. Choices and considerations for in-centre versus home-based renal replacement therapy. Edited by David J. Goldsmith. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0144.

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There has been a renewed global interest in expanding home dialysis (both peritoneal dialysis (PD) and home haemodialysis (HHD)), but the majority of patients are maintained on in-centre haemodialysis (HD). While the importance of in-centre haemodialysis cannot be overlooked, home dialysis has many advantages. If so, why are so few patients maintained on home dialysis therapies? From the perspective of the patient, both inadequate modality education and self-perceived barriers limit selection of home dialysis. Physicians are less likely to consider elderly frail patients as candidates for home therapies. In addition, inadequate training and poor reimbursement for home dialysis are important physician barriers. From the facility perspective, the limited availability of personnel and physical resources to maintain a home unit are important barriers. However, while there are many obstacles to home dialysis, they can be overcome. Improved patient education, home support for elderly dialysis patients, and financial incentives may be effective measures. In addition, at the facility level, an emphasis needs to be placed on infrastructure development. Overall, while the appropriate balance of in-centre versus home-based renal replacement therapy has not been determined, maximizing the number of patients on home therapies is a reasonable target.

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30

Cassidy, Jim, Donald Bissett, Roy A. J. Spence OBE, Miranda Payne, and Gareth Morris-Stiff. Surgical oncology. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199689842.003.0003.

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Cancer is a disease of the genes. In the last two decades new technologies have allowed us to interrogate the genome more efficiently and faster. This has led to new therapies and improved understanding of cancers. It is clear the few cancers are caused by just one gene defect and in these rare cases the defective gene or its product is a target for therapeutic intervention. The bigger challenge now is to use this paradigm against multi-genic cancers which are far more common and more complex in their genetic makeup.

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31

Shils, Jay L., Sepehr Sani, Ryan Kochanski, Mena Kerolus, and Jeffrey E. Arle. Recording Techniques Related to Deep Brain Stimulation for Movement Disorders and Responsive Stimulation for Epilepsy. Edited by Donald L. Schomer and Fernando H. Lopes da Silva. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190228484.003.0038.

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Neuromodulation therapies are now common treatments for a variety of medically refractory disorders, including movement disorders and epilepsy. While surgical techniques for each disorder vary, electricity is used by both for relieving symptoms. During stereotactic placement of the stimulating electrode, either deep brain stimulation electrodes or cortical strip electrodes, intraoperative neurophysiology is used to localize the target structure. This physiology includes single-unit recordings, neurostimulation evoked response evaluation, and intracranial electroencephalography (EEG) to ensure the electrode leads are in the optimal location. Because the functional target for the responsive neurostimulator is more easily visualized on preoperative magnetic resonance imaging, intraoperative physiology is used more as a confirmatory tool, in contrast to the more functional localization-based use during electrode placement for movement disorders. This chapter discusses surgical placement of the electrodes for each procedure and the physiological guidance methodology used to place the leads in the optimal location.

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32

Coghlan, J. Gerry, and Benjamin E. Schreiber. Cardiovascular system. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0019.

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Rheumatology, as a specialty that encounters many multisystem diseases, requires knowledge of many of the more exotic cardiovascular conditions including large- and small-vessel vasculitis, pulmonary hypertension, and myopericarditis. In addition, many rheumatology patients will suffer from cardiovascular pathology due to its common nature and association with an older population, since many previously lethal conditions are now associated with better survival. This requires a detailed knowledge of the drug—drug interactions that arise and the off-target consequences of rheumatological therapies that may aggravate atheroma and hypertension. The rheumatologist therefore needs a broad knowledge of cardiovascular diseases.

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33

Coghlan, J. Gerry, and Benjamin E. Schreiber. Cardiovascular system. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199642489.003.0019_update_002.

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Rheumatology, as a specialty that encounters many multisystem diseases, requires knowledge of many of the more exotic cardiovascular conditions including large- and small-vessel vasculitis, pulmonary hypertension, and myopericarditis. In addition, many rheumatology patients will suffer from cardiovascular pathology due to its common nature and association with an older population, since many previously lethal conditions are now associated with better survival. This requires a detailed knowledge of the drug—drug interactions that arise and the off-target consequences of rheumatological therapies that may aggravate atheroma and hypertension. The rheumatologist therefore needs a broad knowledge of cardiovascular diseases.

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34

Gan, Li. Cellular Mechanisms of Dementia. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0054.

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Neurodegenerative dementias, including Alzheimer’s disease (AD), Parkinson’s disease (PD) and Frontotemporal dementia (FTD), pose enormous challenges for our aging society. Genetic and mechanistic studies have revealed common molecular and cellular pathways, including imbalanced proteostasis and aberrant innate immune responses. Key pathogens in AD, PD, and FTD accumulate and spread from one brain region to another, resulting in network dysfunction and cognitive decline. These diseases are multifactorial, caused by interactions among multiple genetic, epigenetic, and environmental factors and pathways. Combination therapies that target multiple pathways may also be needed to stop or delay the dementing conditions in neurodegenerative dementias.

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35

Foo, Joanne, Benazir Saleem, and Philip G. Conaghan. Analgesics. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0078.

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Pain is one of the commonest presenting symptoms of musculoskeletal disorders and may be one the hardest to treat successfully. The available analgesic options provide different modes of action and their ranks continue to expand with new agents, some with multiple target action. This chapter reviews currently available analgesics (paracetamol and opioids) used for managing musculoskeletal pain and the agents used for neuropathic pain, including their mechanism of action, pharmacokinetics and side effects. The role of neuroleptic agents is reviewed, and a brief outline of some newer therapies for the treatment of pain such as tapentadol, and a potential therapy, anti-nerve growth factor monoclonal antibodies.

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36

Targeted Therapies in Oncology. CRC Press, 2013.

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37

Giaccone, Giuseppe, and Jean-Charles Soria. Targeted Therapies in Oncology. Taylor & Francis Group, 2019.

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38

Giaccone, Giuseppe, and Jean-Charles Soria. Targeted Therapies in Oncology. Taylor & Francis Group, 2013.

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39

Giaccone, Giuseppe, and Jean-Charles Soria. Targeted Therapies in Oncology. Taylor & Francis Group, 2013.

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40

Giaccone, Giuseppe, and Jean-Charles Soria. Targeted Therapies in Oncology. Taylor & Francis Group, 2007.

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41

Ritchie, Elspeth Cameron, Perry R. Chumley, Meg Daley Olmert, Rick A. Yount, Matthew St Laurent, and Christina Rumayor. Canines as Assistive Therapy for Treatment of PTSD. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190205959.003.0008.

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Canine-assisted therapies are being used increasingly both by veterans and the civilian community for mental and emotional support. During the past decade, a growing body of scientific research has provided evidence that human–animal interactions can improve social competence and reduce physiological, psychological, and behavioral effects of stress and social isolation. One meta-analysis that evaluated 49 published studies of animal-assisted therapy (AAT), used mainly to target mental health concerns, concluded that AAT is effective for medical well-being, for behavioral outcomes in adults, and for improving the therapy participation of children with autism and related disorders. The study also found that AAT was as effective as other interventions examined in comparison.

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42

Holmqvist, Rolf. Client and Therapist Reports. Edited by Sara Maltzman. Oxford University Press, 2016. http://dx.doi.org/10.1093/oxfordhb/9780199739134.013.36.

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Testing efficacy and effectiveness of psychological treatment requires valid and reliable methods for describing change. There are three main issues in rating outcome: First, from what perspective should the ratings be made (client, therapist, society)? Second, what level should the measurement target (concrete behavior or thought, syndrome, or global change)? Third, should outcome be described nomothetically (with standardized instruments) or ideographically? Despite many proposals over the years, there is still no consensus about instruments that make comparisons between studies comparable. Some scales have, however, become standard for specific disorders. Comparisons of ratings by clients and therapists show moderate agreement about presenting problems, perception of the process (e.g., alliance), and outcome. One reason for imperfect agreement may be different formulations and instruments for each participant. Another reason could be that clients and therapists have different perspectives on how to describe problems and therapy activities conceptually. It may be important to distinguish between clients’ and therapists’perceptionsof agreement, for instance about activities in therapy and goals, andactualagreement on specific behaviors and targets. Although agreement may be important, recent theories and studies have emphasized that a mutual therapeutic endeavor can be characterized as an ongoing negotiation between client and therapist. The negotiation in itself may be a potent therapeutic tool. Therapists are encouraged to follow the development of clients’ ratings of both symptoms and alliance continuously during treatment in order to modify the treatment in accordance with the current level of symptoms as well as the clients’ perspective on the therapeutic collaboration.

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43

Targeted Therapies In Breast Cancer. Clinical Publishing Services, 2012.

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44

Cho, C. H. Therapeutic Targets for Inflammation and Cancer: Novel Therapies for Digestive Diseases. World Scientific Publishing Co Pte Ltd, 2017.

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45

Noble, James M. Navigating Life with Dementia. Oxford University PressNew York, 2022. http://dx.doi.org/10.1093/oso/9780190495688.001.0001.

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Abstract This book begins by establishing a shared understanding of key terms used when describing dementia and explaining how dementia differs from the normal changes of aging. It then discusses the process of establishing a diagnosis, explains how the brain works in the process, and takes a deep dive into each of the most common types of dementia. The book also explores treatments, including standard medical therapies for the symptoms of dementia, evolving treatments that target the biology of disease to potentially slow the course, and complementary strategies to support the patient and caregiver/care partner, as well as the option of participating in research. It features patient stories to help in understanding how problems may emerge in daily life. Ultimately, the book serves a dual purpose: to help in day-to-day challenges and in understanding what lies ahead.

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46

Khanna, Puja. Treatment of acute gout. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199668847.003.0045.

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Acute gout is a common inflammatory arthritis in the adult population. Epidemiological evidence suggests that the prevalence of gout is steadily on the rise due to longevity, coexisting comorbidities, and iatrogenic causes contributing to hyperuricaemia. Acute gout usually presents as a self-limiting flare of synovitis that occurs due to deposition of monosodium urate crystals. The frequency of flares generally increases over time in patients who continue to have hyperuricaemia and their risk factors for acute gout attacks have not been adequately addressed. Effective treatment of acute gouty arthritis is primary focused on pain which is the primary symptom but must target both the pain and underlying inflammation. Acute gout is frequently treated with non-steroidal anti-inflammatory agents, colchicine, and corticosteroids. This chapter reviews the available therapies for management of acute gout and ones that have shown promising results.

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47

Los, Marek, and Spencer B. Gibson. Apoptotic Pathways As Targets for Novel Therapies in Cancer and Other Diseases. Springer London, Limited, 2006.

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48

(Editor), Marek Los, and Spencer B. Gibson (Editor), eds. Apoptotic Pathways as Targets for Novel Therapies in Cancer and Other Diseases. Springer, 2005.

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49

Los, Marek, and Spencer B. Gibson. Apoptotic Pathways As Targets for Novel Therapies in Cancer and Other Diseases. Springer, 2014.

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Mease, Philip. Biologic treatments for psoriatic arthritis apart from TNF inhibition. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198737582.003.0030.

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Анотація:

Psoriatic arthritis (PsA) is an immunologically mediated inflammatory disease characterized by arthritis, enthesitis, dactylitis, spondylitis, and psoriasis. Prior to the introduction of targeted biologic medications, such as TNF inhibitors, the ability to control disease activity was limited, with only modest effects noted with traditional oral medications such as methotrexate and sulfasalazine. The introduction of TNF inhibitors substantially changed the outlook of PsA patients, yielding significant response in all relevant clinical domains and demonstrating the ability to inhibit progressive structural damage of joints. However, not all patients responded to these agents and many patients displayed initial response which waned over time, partly due to immunogenicity (development of antibodies which blocked full therapeutic effect of the biologic protein), or because of tolerability and side effect issues. Thus, it has been important to develop new medicines which target other key cytokines and immunologic pathways. Several medicines with a different mechanism of action have been approved or are in development for the treatment of PsA. Ustekinumab inhibits both IL12 and IL23 and thus is felt to work in both the TH1 and TH7 pathways of inflammation. The oral medicine apremilast inhibits phosphodiesterase 4, thus modulating the cyclic AMP pathway in immunologic cells, yielding an anti-inflammatory effect. Both of these medicines have been approved for the treatment of PsA as well as psoriasis. An emerging group of therapies, the IL17 inhibitors, has demonstrated significant effectiveness in psoriasis and PsA and one of these, Secukinumab, has been approved for psoriasis, PsA, and AS. Other medicines in development include the co-stimulatory blockade agent, abatacept, oral Janus Kinase (JAK) inhibitors, and an emerging group of therapies which inhibit IL23. As modulators of immune cell function, these agents have the potential to increase risk for infection, as well as other side effects. These must be discussed with the patient and considered when determining overall risk benefit analysis regarding their use. The emergence of medicines with a different mechanism of action than TNF inhibition has broadened and strengthened our ability to effectively treat PsA.

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