#3-01E. Efficacy vs. Safety: The Cumulative Evidence on JAK Inhibitors in RA (Semin Arthritis Rheum, 2025)

In the management of rheumatoid arthritis, balancing the rapid relief of oral therapies against potential long-term risks remains a critical clinical challenge. This systematic review and cumulative meta-analysis of 46 randomized controlled trials evaluates the trajectory of evidence regarding Janus kinase (JAK) inhibitors compared to placebo and active comparators. The study confirms that JAK inhibitors consistently demonstrate superior efficacy in improving DAS28 scores and physical function from the earliest trials. However, the core finding highlights a significant temporal lag in safety data: increased risks of major adverse cardiovascular events (MACE) and serious adverse events versus bDMARDs only reached statistical significance with the addition of recent, large-scale post-marketing data like the ORAL Surveillance trial. Critically, physicians should recognize that earlier trials were insufficiently powered with too short a follow-up to detect these rare outcomes, limiting early risk identification. For clinical practice, this underscores the necessity of weighing the advantage of fast-acting symptom control against cardiovascular risks, necessitating careful, individualized patient selection and ongoing pharmacovigilance.Citation: O’Neill, S.M. et al. The efficacy and safety of Janus kinase inhibitors in adults with rheumatoid arthritis: a systematic review and cumulative meta-analysis. Seminars in Arthritis and Rheumatism. 2025.

DOI: 10.1016/j.semarthrit.2025.152885

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