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Systemic Treatment of Psoriasis with JAK Inhibitors: A Review.

Published on Feb 1, 2020in Dermatologic Therapy1.74
· DOI :10.1007/S13555-019-00347-W
Amanda Kvist-Hansen (UCPH: University of Copenhagen), Peter Riis Hansen49
Estimated H-index: 49
(UCPH: University of Copenhagen),
Lone Skov37
Estimated H-index: 37
(UCPH: University of Copenhagen)
Abstract
Psoriasis is a prevalent chronic inflammatory disease. The inflammatory response is driven by T cells and mediated by multiple cytokines such as tumor necrosis factor and the interleukins IL-17 and IL-23. Moderate-to-severe psoriasis is treated systemically, using either biologics or conventional treatments with small-molecule drugs. The newer biologics are very effective and well tolerated, but not all patients respond to treatment with biologics, so there is a need for new treatment options for psoriasis. Janus kinase (JAK) inhibitors are a new drug class that may be of use in this respect. These inhibitors are already on the market for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. They block the intracellular signal pathway mediated by JAK and signal transducer and activator of transcription (STAT) proteins, thereby inhibiting gene transcription of proinflammatory cytokines. JAK inhibitors are currently being tested as potential treatments for psoriasis. They have shown clinical efficacy as measured by the Psoriasis Area and Severity Index 75 response in both phase 2 and 3 trials, and appear to be well tolerated overall. This review provides an overview of the mechanisms underlying the actions of JAK inhibitors in psoriasis, together with the results of clinical trials testing their efficacies when used to treat the disease.
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References39
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#2Kristen M. BeckH-Index: 6
Last. Wilson LiaoH-Index: 29
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Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of psoriatic arthritis (PsA). It provides an alternative option for patients who have had an inadequate response and tolerance to other disease modifying antirheumatic drugs (DMARDs). It has demonstrated comparable efficacy to biologics, is effective in the management of treatment resistant disease, and is reported to improve enthesitis, dactylitis, and radiographic progression. Tofacitinib is also associated with an increa...
1 CitationsSource
#1L SawyerH-Index: 2
Last. Richard B. Warren (Salford Royal NHS Foundation Trust)H-Index: 32
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Introduction New generation biologics, including interleukin (IL)-17 and IL-23 inhibitors, have delivered higher rates of skin clearance than older treatments in head-to-head studies. However, studies comparing these new biologics directly to one another are limited. Objectives To compare the short-term efficacy of available (or imminently available) biologic and non-biologic systemic therapies for treating patients with moderate-to-severe plaque psoriasis. Methods A systematic review was undert...
4 CitationsSource
#1Kata Szilveszter (Semmelweis University)H-Index: 1
#2Tamás Németh (Semmelweis University)H-Index: 11
Last. Attila Mócsai (Semmelweis University)H-Index: 39
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Tyrosine kinases relay signals from diverse leukocyte antigen receptors, innate immune receptors and cytokine receptors, and therefore mediate the recruitment and activation of various leukocyte populations. Non-receptor tyrosine kinases of the Jak, Src, Syk and Btk families play major roles in various immune-mediated disorders, and small-molecule tyrosine kinase inhibitors are emerging novel therapeutics in a number of those diseases. Autoimmune and inflammatory skin diseases represent a broad ...
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#2Dibyabhaba Pradhan (ICMR: Indian Council of Medical Research)H-Index: 11
Last. Arun Kumar Jain (ICMR: Indian Council of Medical Research)H-Index: 8
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Abstract Psoriasis is an immune mediated inflammatory skin disease with complex etiology involving interplay between environmental and genetic risk factors as disease initiating event. Enhanced understanding on genetic risk factors, differentially expressed genes, deregulated proteins and pathway-targeted therapeutics have established multiple axis of psoriasis pathogenesis. So far, loci in 424 genes are reported to be associated with psoriasis alongside copy number variations and epigenetic alt...
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ABSTRACTIntroduction: Tyrosine kinase 2 (Tyk2) is a non-receptor tyrosine-protein kinase, an enzyme that in humans is encoded by the TYK2 gene. Tyk2, together with three other family subtypes, name...
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Abstract Background Tyrosine kinase 2 (TYK2) signaling pathways, which mediate cytokine signaling, are implicated in the pathophysiology of psoriasis. Selective inhibitors of TYK2 may be effective in treating psoriasis. Methods We conducted a phase 2, double-blind trial of a TYK2 inhibitor, BMS-986165, in adults with moderate-to-severe psoriasis, excluding patients with a previous lack of response to agents targeting cytokine signaling through the same tyrosine kinase pathway. Patients were rand...
25 CitationsSource
#1Alexander Egeberg (UCPH: University of Copenhagen)H-Index: 19
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Last. L. Skov (UCPH: University of Copenhagen)H-Index: 15
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Background Real-life data on newer biologic and biosimilar agents for moderate-to-severe psoriasis are lacking. Objectives To examine safety, efficacy, and time to discontinuation (drug survival) of biologics (adalimumab, etanercept, infliximab, secukinumab, and ustekinumab) and compare originators with biosimilars (i.e. Enbrel with Benepali, and Remicade with Remsima). Methods The DERMBIO registry contains data on all Danish patients with moderate-to-severe plaque psoriasis treated with biologi...
52 CitationsSource
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Shih and colleagues analyse comprehensive industry-wide data on drug development projects pursued during the past 20 years, classified according to the mechanism and indication for each project. Their findings indicate several points and trends that may be useful in understanding and improving the productivity of the pharmaceutical industry, including areas with substantial success or failure and the relative extent of novelty in completed and ongoing projects.
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