Obesity

An individual patient data meta-analysis of 16 phase 3 trials and 11,883 patients shows JAK inhibitor response falls in a graded way as BMI rises — roughly 18 fewer ACR20 responders per 100 treated at class 3 obesity. Crucially, no such gradient appears in the placebo arms, and within-trial interaction analyses confirm obesity modifies the treatment effect rather than simply marking worse disease.

A 2026 clinical-pharmacology perspective arguing that biologic treatment failure in obesity is partly a pharmacokinetic problem: weight-driven clearance leaves many patients on fixed-dose subcutaneous biologics systematically underdosed, and dosing strategy should be matched to the weight–clearance relationship.