Obesity blunts the response to JAK inhibitors in rheumatoid arthritis

The edition in brief

Today's rheumatology desk leads on weight. An individual patient data meta-analysis of 11,883 people across 16 phase 3 JAK inhibitor trials found response falling as BMI rose, with adjusted relative risk for ACR20 dropping to 0.78 at class 3 obesity. No such gradient appeared in the placebo arms, which is what makes this a drug effect rather than a general observation that heavier patients do worse. It is a reason to treat weight as part of the treatment plan, not a separate conversation. A dose-response meta-analysis of resistance training for knee osteoarthritis found the benefit is not linear: pain relief peaked around 6,000 repetitions, function around 2,600 at moderate intensity, and strength around 1,600. Certainty was low to very low, so these are directions rather than prescriptions, but they argue against the assumption that more is always better. Two biomarker papers point the same way. DNA methylation of the TNFA gene predicted methotrexate-induced remission in early rheumatoid arthritis and added to a model built on clinical data alone, but did nothing in psoriatic arthritis. High baseline interleukin-10 predicted better response to abatacept plus methotrexate and less bone erosion. On the regulatory side, the FDA cleared a supplemental application for YUSIMRY, an adalimumab biosimilar. It changes no indication, but biosimilar supply is what decides whether an Indian patient starts a biologic at all.