This was an individual-patient-data meta-analysis pooling 16 randomised trials and 11,883 patients from the tofacitinib, upadacitinib and baricitinib programmes — the strongest design for this question, because it re-analyses each patient rather than trial averages.
Higher BMI was associated with a stepwise fall in the chance of an ACR20 response. Compared with healthy weight, the adjusted relative risk 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 worsened along the same gradient. Importantly, no such gradient appeared in the placebo groups, so this reflects reduced drug benefit, not just heavier patients faring worse.
In practice this argues for making weight management part of the treatment plan rather than an afterthought, and for setting expectations honestly with a patient who has class 2–3 obesity starting a JAK inhibitor. It is an association from trial populations, not a reason to withhold an effective drug, but it should inform the conversation.
- ACR20 response fell as BMI rose: RR 0.78 in class 3 obesity versus healthy weight
- Same gradient on DAS28-CRP; absent in placebo groups, so it is drug-specific
- Fold weight management into the RA treatment plan, not alongside it as an afterthought
- Set realistic expectations before starting a JAK inhibitor at high BMI
The statistics, in plain English
A relative risk of 0.78 for ACR20 in class 3 obesity means these patients were about 22% less likely to reach that response than healthy-weight patients on the same drug; the interval (0.71–0.85) stays below 1.0, so the reduction is statistically clear. The step-by-step fall across weight categories, and its absence under placebo, is what makes obesity look like a true effect modifier rather than a confounder.
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