Design: Individual patient data meta-analysis of 16 phase 3 randomised trials
Population: 11,883 adults with RA in tofacitinib, baricitinib and upadacitinib trials
Primary outcome: ACR20 and DAS28-CRP at primary timepoint
Effect: ACR20 RR 0.94 (overweight) to 0.78 (0.71-0.85, class 3 obesity) vs healthy weight

This individual patient data meta-analysis used 16 phase 3 trials of tofacitinib, baricitinib and upadacitinib, with 11,883 participants; 30.9% had obesity.

Compared with healthy weight, the relative risk of ACR20 response was 0.94 for overweight, 0.92 for class 1 obesity, 0.88 for class 2 and 0.78 for class 3 (95% CI 0.71-0.85). DAS28-CRP was worse by 0.14 to 0.54 across the same categories. No BMI gradient was seen on placebo. Heterogeneity was low to moderate.

The absence of a gradient on placebo suggests obesity modifies the drug effect itself rather than simply marking harder-to-treat disease. The effect is modest in overweight patients but meaningful in severe obesity.

Weight management belongs in RA care alongside drug choice, particularly before judging a JAK inhibitor to have failed in a patient with severe obesity.

Record BMI when starting an advanced therapy.
Offer weight management support to patients with obesity and active RA.
Factor severe obesity into expectations of JAK inhibitor response.
Remember that obesity also raises cardiovascular and thrombotic risk relevant to JAK inhibitors.

Why it matters

It shows obesity reduces the drug's effect, not just the patient's baseline, which changes how treatment failure should be interpreted.

The statistics, in plain English

A relative risk of 0.78 means patients with class 3 obesity were about 22% less likely to achieve ACR20 than those at healthy weight. The finding that placebo response did not vary with BMI is what makes this an effect modification rather than confounding.