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Thromboembolism with Janus Kinase (JAK) Inhibitors for Rheumatoid Arthritis: How Real is the Risk?

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Abstract

Two different Janus kinase (JAK) inhibitors—baricitinib and tofacitinib—are effective and licensed in active rheumatoid arthritis (RA). There have been recent concerns about potential thromboembolic risks with these drugs. Concerns about baricitinib focus on clinical trial findings. Using all publically available data, we estimate thromboembolic risks are approximately five events per 1000 patient years with 4 mg baricitinib daily. Concerns about tofacitinib have been raised by analyses of the Federal Drug Administration Adverse Event Reporting System (FAERs). These show some evidence of increased risks of pulmonary thrombosis, though not pulmonary embolism or venous thrombosis. Observational studies suggest in the general population and non-RA controls there are one to four thromboembolic events per 1000 patient years. In RA, thromboembolic risks increase to three to seven per 1000 patient years. The impact of biologics and disease-modifying anti-rheumatic drugs (DMARDs) on disease risk appears minimal, and the number of thromboembolic events is between four and eight per 1000 patient years. In the short term, full details of thromboembolic events in trials of JAK inhibitors need to be published. As the numbers of thromboembolic events will be small and patients enrolled in trials are not representative of all RA patients who may receive JAK inhibitors, this information is unlikely to provide definitive answers. Consequently, in the longer term, large observational studies are needed to accurately quantify thromboembolic risks attributable to JAK inhibitors and other drugs used to treat RA, and differentiate these from risks attributable to RA itself and its comorbidities.

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Authors and Affiliations

  1. Research Institute for Primary Care & Health Sciences, Primary Care Sciences, Keele University, Keele, Staffordshire, UK

    Ian C. Scott & Samantha L. Hider

  2. Haywood Academic Rheumatology Centre, Haywood Hospital, High Lane, Burslem, Staffordshire, UK

    Ian C. Scott & Samantha L. Hider

  3. Academic Rheumatology, King’s College Hospital, London, UK

    David L. Scott

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Correspondence to David L. Scott.

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Conflict of interest

Dr. Ian Scott is the statistician on a retrospective study entitled “Factors Associated with Disability in Rheumatoid Arthritis (RA) Patients with Persistent Medium Disease Activity (MDAS)”. This study is being conducted by Guy’s and St Thomas’ NHS Trust and sponsored by Eli Lilly. Dr. Scott will be receiving funding for this work from Guy’s and St Thomas’ NHS Trust in the future. He has no other potential conflicts of interest directly relevant to this study. Dr. Samantha Hider has no conflicts of interest that are directly relevant to the content of this study. Professor David L. Scott has received fees for consulting and giving educational lectures from Eli Lilly and Co. of less than £5000 in the last 5 years, but none since 2015. He has no other potential conflicts of interest directly relevant to this study.

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Scott, I.C., Hider, S.L. & Scott, D.L. Thromboembolism with Janus Kinase (JAK) Inhibitors for Rheumatoid Arthritis: How Real is the Risk?. Drug Saf 41, 645–653 (2018). https://doi.org/10.1007/s40264-018-0651-5

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