JAK inhibitors worked less well as BMI rose, across nearly 12,000 patients

The edition in brief

This individual patient data meta-analysis obtained participant-level data through the Vivli platform for 16 phase 3 randomised trials of tofacitinib, baricitinib and upadacitinib in rheumatoid arthritis, covering 11,883 participants. Median BMI was 26.8 kg/m2 and 30.9% had class 1-3 obesity. Higher BMI was associated with reduced efficacy across every endpoint, in a clear stepwise pattern. Compared with healthy weight, adjusted relative risk for ACR20 response was 0.94 (95% CI 0.91-0.98) for overweight, 0.92 (0.89-0.96) for class 1 obesity, 0.88 (0.81-0.96) for class 2, and 0.78 (0.71-0.85) for class 3 obesity. DAS28-CRP showed the same gradient. Critically, no corresponding BMI gradient appeared in the placebo groups, which argues that this reflects reduced drug effect rather than obesity simply worsening disease measurement. Heterogeneity was low to moderate and risk of bias low. An international taskforce from three lupus expert groups has published consensus therapeutic strategies for 22 further rare manifestations of systemic lupus erythematosus, including diffuse pulmonary haemorrhage, lupus podocytopathy, catatonia, protein-losing enteropathy and interstitial cystitis, adding to 24 previously covered. Across five Nordic registries and 14,362 patients with psoriatic arthritis, 36% discontinued at least two biologic or targeted synthetic DMARDs, but only 2% met difficult-to-manage criteria and 1.2% treatment-refractory criteria.