#5-46E. Attenuated Response: How Obesity Acts as a True Effect Modifier of JAK Inhibitors in Rheumatoid Arthritis (Lancet Rheumatol, 2026)

Does body weight compromise the clinical efficacy of Janus kinase inhibitors in our rheumatoid arthritis patients? This comprehensive meta-analysis of individual patient data from 16 phase 3 randomized controlled trials, comprising 11,883 participants, investigated how body mass index (BMI) influences response to JAK inhibitors. The study revealed a clear, graded reduction in clinical response (including ACR20 and DAS28-CRP outcomes) with increasing BMI. Crucially, obesity acts as a true, drug-specific effect modifier rather than a general prognostic factor, as no corresponding BMI-related trend was observed in the placebo cohort. However, a key limitation is the restriction to phase 3 clinical trials, which may limit generalisability to real-world populations, alongside the lack of longitudinal data on weight changes since BMI was only recorded at baseline. For clinicians, these findings suggest that escalating JAK inhibitor doses—which raises safety concerns—is not a viable solution; instead, integrating structured weight management into routine rheumatological care is essential to optimize therapeutic outcomes in patients with higher BMI.

Citation: Bechman, K., Russell, M. D., Biddle, K., Gibson, M., Brown, J., Rutherford, A. I., Nikiphorou, E., Perucha, E., Cope, A. P., Norton, S., and Galloway, J. Impact of BMI on response to Janus kinase inhibitors in rheumatoid arthritis: an individual patient data metaanalysis of randomised controlled trials. The Lancet Rheumatology. 2026. DOI: 10.1016/S2665-9913(26)00151-7

URL: https://doi.org/10.1016/S2665-9913(26)00151-7

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