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Review
. 2021 May 5;60(Suppl 2):ii24-ii30.
doi: 10.1093/rheumatology/keaa895.

The safety of JAK-1 inhibitors

Benjamin Clarke  1 , Mark Yates  1 , Maryam Adas  1 , Katie Bechman  1 , James Galloway  1
Affiliations
Review

The safety of JAK-1 inhibitors

Benjamin Clarke et al. Rheumatology (Oxford). .

Abstract

As efficacy and safety data emerge, differences between JAK inhibitor subclasses are appearing. JAK1 selective drugs, upadacitinib and filgotinib, have broadly come with the same overarching safety recommendations as other immunosuppressive drugs for RA: caution is needed regarding infection risk; monitoring for laboratory abnormalities, including lipids and muscle enzymes, is indicated. A distinguishing feature of JAK inhibitors is a risk for zoster reactivation. Numerically, overall rates of serious infection are similar among JAK inhibitor classes. There are currently no signals for diverticular perforation. VTE incidence rates were similar across comparator groups for the JAK1 selective agents. These observations are not yet conclusive evidence for different safety profiles between JAK1 selective agents and other JAK inhibitors. Differences in study population, design, and concomitant steroid use are examples of potential confounders. It is too early to draw conclusions on long-term outcomes such as malignancy and cardiovascular risk. Post-marketing pharmacovigilance studies will be essential.

Keywords: JAK inhibitor; pharmacovigilance; rheumatoid arthritis; safety; trials; zoster.

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Figures

<sc>Fig</sc>. 1
Fig. 1
JAK transmembrane receptor signalling pathways
See this image and copyright information in PMC

References

    1. Burmester GR, Kremer JM, Van den Bosch F. et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (SELECT-NEXT): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2018;391:2503–12. - PubMed
    1. Fleischmann RM, Genovese MC, Enejosa JV. et al. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis 2019;78:1454–62. - PMC - PubMed
    1. Genovese MC, Fleischmann R, Combe B. et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet 2018;391:2513–24. - PubMed
    1. Smolen JS, Pangan AL, Emery P. et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. The Lancet 2019;393:2303–11. - PubMed
    1. Vollenhoven R, Takeuchi T, Pangan AL. et al. Efficacy and safety of upadacitinib monotherapy in methotrexate-naive patients with moderately to severely active rheumatoid arthritis (SELECT-EARLY): a randomized, double-blind, active-comparator, multi-center, multi-country trial. Arthritis Rheumatol 2020;72:1607–20. - PMC - PubMed

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