AN INDIVIDUAL patient data meta-analysis has revealed that higher BMI significantly reduces the effectiveness of JAK inhibitors in rheumatoid arthritis, with obesity acting as a true modifier of treatment response rather than simply a marker of worse prognosis.
Obesity has been recognised as common among patients with rheumatoid arthritis and has been associated with poorer disease outcomes. Previous pooled analyses have suggested that JAK inhibitor efficacy is broadly maintained across standard body mass index categories, although these studies have not formally tested whether body mass index modifies treatment effect versus placebo.
Researchers conducted an individual patient data meta-analysis of phase 3 randomised trials of tofacitinib, baricitinib, upadacitinib, and filgotinib in adults with rheumatoid arthritis, identified via ClinicalTrials.gov and obtained through the Vivli data-sharing platform.
Body mass index was analysed as a continuous and categorical variable using one-stage mixed-effects models, validated using a two-stage meta-analysis. Primary outcomes were a 20% improvement based on American College of Rheumatology core set variables and Disease Activity Score based on 28 joints and C-reactive protein.
Sixteen trials contributed individual patient data from 11,883 participants (80.7% women; mean age 52.9 years), of whom 7,765 received tofacitinib, upadacitinib, or baricitinib; filgotinib trials were excluded due to insufficient variables. Median body mass index was 26.8 kg/m² (IQR 23.2 to 31.3), and 30.9% had class 1-3 obesity.
Higher body mass index was associated with reduced JAK inhibitor efficacy across all endpoints. Compared with healthy weight, the adjusted relative risk for a 20% improvement response was 0.94 (95% CI 0.91 to 0.98) for overweight, 0.92 (0.89 to 0.96) for class 1 obesity, 0.88 (0.81 to 0.96) for class 2 obesity, and 0.78 (0.71 to 0.85) for class 3 obesity.
For disease activity scores, adjusted mean differences versus healthy weight were 0.14 (95% CI 0.06 to 0.22) for overweight, rising to 0.54 (0.37 to 0.70) for class 3 obesity. No corresponding gradient was seen in the placebo group, and between-study heterogeneity was low to moderate.
These findings have shown that higher body mass index is associated with poorer response and reduced treatment benefit from JAK inhibitors, with obesity identified as a true effect modifier rather than merely a marker of prognosis.
The authors have suggested that weight management should be integrated into routine rheumatoid arthritis care alongside pharmacological treatment.
Reference
Bechman K et al. Impact of BMI on response to Janus kinase inhibitors in rheumatoid arthritis: an individual patient data meta-analysis of randomised controlled trials. The Lancet Rheumatology. 2026;DOI:10.1016/S2665-9913(26)00151-7.
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