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Review
. 2021 Feb;51(1):278-284.
doi: 10.1016/j.semarthrit.2020.10.008. Epub 2020 Dec 18.

The Jak/STAT pathway: A focus on pain in rheumatoid arthritis

Lee S Simon  1 , Peter C Taylor  2 , Ernest H Choy  3 , Anthony Sebba  4 , Amanda Quebe  5 , Kelly L Knopp  5 , Frank Porreca  6
Affiliations
Free article
Review

The Jak/STAT pathway: A focus on pain in rheumatoid arthritis

Lee S Simon et al. Semin Arthritis Rheum. 2021 Feb.
Free article

Abstract

Pain is a manifestation of rheumatoid arthritis (RA) that is mediated by inflammatory and non-inflammatory mechanisms and negatively affects quality of life. Recent findings from a Phase 3 clinical trial showed that patients with RA who were treated with a Janus kinase 1 (Jak1) and Janus kinase 2 (Jak2) inhibitor achieved significantly greater improvements in pain than those treated with a tumor necrosis factor blocker; both treatments resulted in similar changes in standard clinical measures and markers of inflammation. These findings suggest that Jak1 and Jak2 inhibition may relieve pain in RA caused by inflammatory and non-inflammatory mechanisms and are consistent with the overarching involvement of the Jak-signal transducer and activator of transcription (Jak/STAT) pathway in mediating the action, expression, and regulation of a multitude of pro- and anti-inflammatory cytokines. In this review, we provide an overview of pain in RA, the underlying importance of cytokines regulated directly or indirectly by the Jak/STAT pathway, and therapeutic targeting of the Jak/STAT pathway in RA. As highlighted herein, multiple cytokines directly or indirectly regulated by the Jak/STAT pathway play important roles in mediating various mechanisms underlying pain in RA. Having a better understanding of these mechanisms may help clinicians make treatment decisions that optimize the control of inflammation and pain.

Keywords: Cytokines; Inflammation; Janus kinases; Pain; Rheumatoid arthritis; STAT.

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Conflict of interest statement

Declaration of Competing Interest L. S. Simon has been a consultant for AbbVie, Amgen, Antares Pharma, Asahi Kasei Pharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, EMD Serono, Gilead Sciences, GlaxoSmithKline, Horizon, Kiniksa, Medac, Novartis, Pfizer, Regeneron, Rigel Pharmaceuticals, Roche, Sandoz, and Sanofi; and is a founder of OsteoAnalgesia; E. H. Choy has been a consultant, has received grant/research support, and/or has been a speaker for: Amgen, Biogen, Biocancer, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Eli Lilly and Company, Hospira, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, R-Pharm, Sanofi-Aventis, and UCB Pharma; A. Sebba has been a consultant and/or speaker for: Amgen, Eli Lilly and Company, Genentech, Gilead Sciences, Novartis, Sanofi, and Regeneron; A. Quebe and K. L. Knopp are employees and shareholders of: Eli Lilly and Company. P. C. Taylor has been a consultant and/or has received grant/research support from: AbbVie, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Fresenius Medical Care, Galapagos NV, Gilead Sciences, GlaxoSmithKline, Janssen, Novartis, Nordic Pharma, Pfizer, Sanofi-Aventis, and UCB Pharma; F. Porreca has served as a consultant or received research funding from Amgen, Acadia Pharmaceuticals, Allergan, BlackThorn Therapeutics, Eli Lilly and Company, Hoba Therapeutics, Ipsen, Nektar, Proximagen, SiteOne Therapeutics, Teva, and Voyager Therapeutics; and is a founder of Catalina Pharma.

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