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Targeted therapies in 2022

JAK inhibitors: new indication and emerging safety data in 2022

Janus kinase inhibitors continue to show promise in a diverse range of indications, but administration of these drugs needs careful consideration of the benefits and risks. Among a plethora of publications in 2022, notable studies explored an important new indication and provided insights into safety concerns.

Key Advances

  • The oral selective tyrosine kinase 2 inhibitor deucravacitinib reduced systemic lupus erythematosus disease activity across multiple domains, with an acceptable safety profile, in the phase II PAISLEY trial1.

  • Cardiovascular and cancer risk was increased in patients treated with tofacitinib compared with a TNF inhibitor in the ORAL Surveillance study, which included patients with rheumatoid arthritis ≥50 years old and who had at least one cardiovascular risk factor2.

  • Overall results of a meta-analysis combining post-marketing data from international sources suggest that the risk of venous thromboembolism is increased in patients treated with baricitinib compared with those treated with a TNF inhibitor3.

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  1. Morand, E. et al. Deucravacitinib, a tyrosine kinase 2 inhibitor, in systemic lupus erythematosus: a phase 2, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. (2022).

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  2. Ytterberg, S. R. et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N. Engl. J. Med. 386, 316–326 (2022).

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  3. Salinas, C. et al. Evaluation of VTE, MACE, and serious infections among patients with RA treated with baricitinib compared to TNFi: a multi-database study of patients in routine care using disease registries and claims databases. Rheumatol. Ther. (2022).

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  4. Winthrop, K. L. & Cohen, S. B. Oral surveillance and JAK inhibitor safety: the theory of relativity. Nat. Rev. Rheumatol. 18, 301–304 (2022).

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  5. Paik, J. J. et al. Use of Janus kinase inhibitors in dermatomyositis: a systematic literature review. Clin. Exp. Rheumatol. (2022).

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  6. Watanabe, R. & Hashimoto, M. Perspectives of JAK inhibitors for large vessel vasculitis. Front Immunol. 13, 881705 (2022).

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  7. McGaugh, S., Kallis, P., De Benedetto, A. & Thomas, R. M. Janus kinase inhibitors for treatment of morphea and systemic sclerosis: A literature review. Dermatol Ther. 35, e15437 (2022).

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Correspondence to Peter Nash.

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Competing interests

The author declares that he has received grants for research and clinical trials and honoraria for advice and lectures from Abbvie, Amgen, BMS, Gilead/Galapagos, Janssen, Lilly, Novartis, Pfizer and Roche.

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Nash, P. JAK inhibitors: new indication and emerging safety data in 2022. Nat Rev Rheumatol 19, 72–73 (2023).

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