Obesity blunts the response to JAK inhibitors in rheumatoid arthritis

The edition in brief

The strongest finding today is that obesity is an effect modifier for JAK inhibitors in rheumatoid arthritis, not just a marker of worse disease. An individual-patient-data meta-analysis of 16 randomised trials and 11,883 patients on tofacitinib, upadacitinib or baricitinib found the chance of an ACR20 response falling as BMI rose: adjusted relative risk versus healthy weight was 0.94 for overweight, 0.92 for class 1 obesity, 0.88 for class 2, and 0.78 for class 3 obesity. DAS28-CRP showed the same gradient, and crucially there was no such gradient in the placebo groups, so this is about drug response rather than heavier patients simply doing worse. It is a reason to fold weight management into the treatment plan and to counsel expectations honestly. On non-drug management, a dose-response meta-analysis of 20 trials in knee osteoarthritis found moderate-intensity isotonic resistance training gave the best results, with pain reductions largest around 6,000 repetitions of accumulated volume and function peaking near 2,600 repetitions of moderate-intensity work; supervised centre-based programmes outperformed home ones, though certainty was low. A diagnostic meta-analysis of 32 studies found deep-learning models grade moderate-to-severe knee osteoarthritis well but remain unreliable for early (Kellgren-Lawrence grade 1) disease, where sensitivity was only 0.66 — not ready for routine screening. On the regulatory side, the sweep picked up another adalimumab biosimilar action (Yusimry, adalimumab-aqvh), relevant mainly to biologic cost and access.