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Review
. 2024 Feb;20(2):101-115.
doi: 10.1038/s41584-023-01062-9. Epub 2024 Jan 12.

Efficacy and safety of JAK inhibitors in rheumatoid arthritis: update for the practising clinician

Zoltán Szekanecz  1 , Maya H Buch  2   3 , Christina Charles-Schoeman  4 , James Galloway  5 , George A Karpouzas  4 , Lars Erik Kristensen  6 , Steven R Ytterberg  7 , Attila Hamar  8 , Roy Fleischmann  9
Affiliations
Review

Efficacy and safety of JAK inhibitors in rheumatoid arthritis: update for the practising clinician

Zoltán Szekanecz et al. Nat Rev Rheumatol. 2024 Feb.

Erratum in

Abstract

Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, upadacitinib and filgotinib, are increasingly used in the treatment of rheumatoid arthritis (RA). There has been debate about their safety, particularly following the issuance of guidance by regulatory agencies advising caution in their use in certain patients. The registrational clinical trials and registry data of JAK inhibitors did not identify a difference in the risk of major adverse cardiovascular events (MACEs), venous thromboembolism, malignancies or infections (other than herpes zoster) with a JAK inhibitor versus a biologic DMARD. In the ORAL Surveillance trial, which enrolled patients >50 years of age with ≥1 cardiovascular risk factor, tofacitinib was statistically inferior to TNF inhibitors for the occurrence of MACEs and malignancy. Further post hoc analysis of the data revealed that an age of ≥65 years, a high baseline cardiovascular risk, a history of smoking, sustained inflammation, disease activity and suboptimal treatment of cardiovascular comorbidities all increase the risk of these outcomes. The guidance issued by regulatory agencies should be carefully considered to ensure appropriate and safe treatment of patients with RA without undertreatment of patients who might benefit from JAK inhibitor, as well as biologic, treatment. As always, the risks associated with the use of these agents, treatment goals, costs and patient preferences should be discussed with the patient.

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References

    1. Smolen, J. S. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann. Rheum. Dis. 82, 3–18 (2023). - PubMed - DOI
    1. Fraenkel, L. et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 73, 1108–1123 (2021). - PubMed - DOI
    1. Smolen, J. S. et al. Rheumatoid arthritis. Nat. Rev. Dis. Primers 4, 18001 (2018). - PubMed - DOI
    1. O’Shea, J. J. Targeting the Jak/STAT pathway for immunosuppression. Ann. Rheum. Dis. 63, ii67–ii71 (2004). - PubMed - PMC
    1. Fleischmann, R. Novel small-molecular therapeutics for rheumatoid arthritis. Curr. Opin. Rheumatol. 24, 335–341 (2012). - PubMed - DOI

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