Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors

Gladman, Dafna D.; Rigby, William F.C.; Azevedo, Valderílio Feijó; Behrens, Frank; Blanco, Ricardo; Kaszuba, Andrzej; Kudlacz, Elizabeth M.; Wang, Cunshan; Menon, Sujatha; Hendrikx, Thijs; Kanik, Keith S.

doi:10.1056/nejmoa1615977

Cited by 437 publications

(509 citation statements)

References 32 publications

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“…Psoriatic arthritis is an autoimmune disease that affects both joints and the skin. Tofacitinib was found to be superior to placebo in patients with psoriatic arthritis who had previously had an inadequate response to conventional disease modifying agents and TNF inhibitors . Tofacitinib is now approved for this indication (Table ).…”

Section: A Brief Survey Of Approved and Late Phase Jakinibsmentioning

confidence: 99%

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Gadina

Johnson

Schwartz

et al. 2018

Journal of Leukocyte Biology

128

100

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In this era, it is axiomatic that cytokines have critical roles in cellular development and differentiation, immune homeostasis, and host defense. Equally, dysregulation of cytokines is known to contribute to diverse inflammatory and immune-mediated disorders. In fact, the past 20 years have witnessed the rapid translation of basic discoveries in cytokine biology to multiple successful biological agents (mAbs and recombinant fusion proteins) that target cytokines. These targeted therapies have not only fundamentally changed the face of multiple immune-mediated diseases but have also unequivocally established the role of specific cytokines in human disease; cytokine biologists have many times over provided remarkable basic advances with direct clinical benefit. Numerous cytokines rely on the JAK-STAT pathway for signaling, and new, safe, and effective small molecule inhibitors have been developed for a range of disorders. In this review, we will briefly summarize basic discoveries in cytokine signaling and briefly comment on some major unresolved issues. We will review clinical data pertaining to the first generation of JAK inhibitors and their clinical indications, discuss additional opportunities for targeting this pathway, and lay out some of the challenges that lie ahead.

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Section: A Brief Survey Of Approved and Late Phase Jakinibsmentioning

confidence: 99%

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Gadina

Johnson

Schwartz

et al. 2018

Journal of Leukocyte Biology

128

100

View full text Add to dashboard Cite

show abstract

“…In our current process, the consensus was to use three swollen and three tender joints as the threshold disease activity measure. This is in line with several other funding guidelines such as the National Institute for Health and Care Excellence (NICE), the British Society for Rheumatology (BSR) and the British Health Professionals in Rheumatology (BHPR) and the French Society for Rheumatology, as well as most clinical trials of biologic therapy in PsA . Baseline swollen and tender joint count, as well as patient and physician global assessment on a Likert scale of 1‐5, should be documented prior to initiation of biologic therapy to enable subsequent response evaluation.…”

Section: Resultsmentioning

confidence: 59%

“…By contrast, there is growing evidence for bDMARDs, with several RCTs demonstrating improved clinical and radiological outcomes in patients naïve to csDMARD as well as in those with failure of csDMARD or tumor necrosis factor inhibitors (TNFi) . However, the high cost prohibits the widespread use of these drugs.…”

Section: Introductionmentioning

confidence: 99%

“…At the time of the literature review for the previous consensus (up to 2013), TNFi were the only licensed bDMARDs for use in PsA. Since then, treatment options have widened with the availability of interleukin‐17 inhibitor (IL17i) secukinumab, IL‐12/23 inhibitor (IL12/23i) ustekinumab, the oral Janus kinase inhibitor tofacitinib and the phosphodiesterase‐4 inhibitor (PDE4i) apremilast …”

Section: Introductionmentioning

confidence: 99%

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Singapore chapter of rheumatologists' updated consensus statement on the eligibility for government subsidization of biologic and targeted therapy for the treatment of psoriatic arthritis

et al. 2019

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Aim There have been major advances in biologic treatment options for psoriatic arthritis (PsA) since the publication of the 2015 consensus recommendations by the Chapter of Rheumatologists, College of Physicians, Academy of Medicine, Singapore, for government‐assisted funding, thus warranting a revision of this guideline. Methods Recent trials and nine published guidelines on the use of biologic therapy for PsA were reviewed. Based on the synthesized evidence, a task force panel (TFP), consisting of 10 practicing rheumatologists in Singapore, rated the statements pertaining to the use of biologic therapy, using a modified Delphi approach. Consensus was obtained if >70% agreed on a statement. Results The TFP agreed on 10 recommendations pertaining to the initiation, choice and continuation of biologic therapy. A biologic is indicated in patients with PsA: (a) with at least three swollen and tender joints, digits or entheses; and (b) who have failed at least two conventional synthetic disease‐modifying anti‐rheumatic drug (csDMARD) strategies for a minimum of 3 months each. Any approved drug class including tumor necrosis factor inhibitors, interleukin‐17 inhibitors (IL‐17i), IL‐12/23i or targeted synthetic DMARDs may be considered as first‐line treatment, and continued only if a response is achieved by 6 months. Conclusion These recommendations developed through a formal consensus method may be useful to guide funding considerations for appropriate and equitable use of biologic therapy for eligible patients with PsA.

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“…A report showed that tofacitinib may lead to the inhibition of the functional effects of IL‐23 on memory T‐cells and suppresses the expression of IL‐23 receptor during the stimulation of lymphocytes . Different studies have reported the effect of tofacitinib on enthesitis in PsA . Although this may not be primary or exclusively driven by affecting IL‐23 secretion, yet we believe that JAKi are unique in their mechanism of action by affecting the production of several cytokine and, in this case, also IL‐23.…”

Section: Pathogenic Role Of Il‐23 In Enthesitis From Clinical Datamentioning

confidence: 82%

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

Bridgewood

Sharif

Sherlock

et al. 2020

Immunological Reviews

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The inflammatory disorders collectively termed the seronegative spondyloarthropathies (SpA) include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, the arthritis associated with inflammatory bowel disease including Crohn's disease and ulcerative colitis, the arthritis related to anterior uveitis, and finally, somewhat controversially Behcet's disease. All of these diseases are associated with SNPs in the IL‐23R or the interleukin‐23 (IL‐23) cytokine itself and related downstream signaling JAK pathway genes and the interleukin‐17 (IL‐17) pathway. In rheumatoid arthritis, the target of the immune response is the synovium but the SpA disorders target the tendon, ligament, and joint capsule skeletal anchorage points that are termed entheses. The discovery that IL‐23R–expressing cells were ensconced in healthy murine enthesis, and other extraskeletal anchorage points including the aortic root and the ciliary body of the eye and that systemic overexpression of IL‐23 resulted in a severe experimental SpA, confirmed a fundamentally different immunobiology to rheumatoid arthritis. Recently, IL‐23R–expressing myeloid cells and various innate and adaptive T cells that produce IL‐17 family cytokines have also been described in the human enthesis. Blockade of IL‐23 pathway with either anti‐p40 or anti‐p19 subunits has resulted in some spectacular therapeutic successes in psoriasis and PsA including improvement in enthesitis in the peripheral skeleton but has failed to demonstrate efficacy in AS that is largely a spinal polyenthesitis. Herein, we discuss the known biology of IL‐23 at the human enthesis and highlight the remarkable emerging story of this unique skeletal tissue.

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Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors

Cited by 437 publications

References 32 publications

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs

Singapore chapter of rheumatologists' updated consensus statement on the eligibility for government subsidization of biologic and targeted therapy for the treatment of psoriatic arthritis

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

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