BMI Affects JAK Inhibitor Responses in Rheumatoid Arthritis

Jack Cush, MD

Sep 03, 2026 5:14 pm

A meta-analysis of Janus kinase (JAKi) inhibitors clinical trials in rheumatoid arthritis (RA) has shown higher BMI was associated with poorer responses and a reduced treatment benefit with JAK inhibitors in RA patients.

Obesity is common (20% to 45%) in patients RA and has been associated with poorer disease outcomes (methotrexate, TNF inhibitors). This study looked at the association between BMI and response to JAKi, using phase 3 trials published on ClinicalTrials.gov (including tofacitinib, baricitinib, upadacitinib, and filgotinib) with a placebo or active comparator.

A total of 16 trials and 11 883 participants (81% women; mean age was 53 years, of whom 7765 received tofacitinib, upadacitinib, or baricitinib.

The Median BMI was 26.8 kg/m² (IQR 23·2–31·3) and 3676 (31%) patients had class 1–3 obesity.

Overall, higher BMI was associated with reduced JAK inhibitor efficacy across all endpoints. Compared with patients with healthy weight, adjusted relative risk for ACR20 responses was:

Overweight (25 to <30 kg/m²) = 0·94 (95% CI 0·91–0·98)
Class 1 obesity (30 to <35 kg/m²) = 0·92 (0·89–0·96)
Class 2 obesity (35 to <40 kg/m²) = 0·88 (0·81–0·96)
Class 3 obesity (≥40 kg/m²) = 0·78 (0·71–0·85)

Compared to normal weight patients the differences (increases) in DAS28-CRP

Overweight (25 to <30 kg/m²) = 0·14 (95% CI 0·06–0·22)
Class 1 obesity (30 to <35 kg/m²) = 0·21 (0·12–0·31)
Class 2 obesity (35 to <40 kg/m²) = 0·30 (0·16–0·44)
Class 3 obesity (≥40 kg/m²) = 0·54 (0·37–0·70)

No corresponding BMI gradient was observed in the placebo group.

Research suggests that intravenous or weight-based dosing strategies of bDMARDS are not particularly effective at overcoming the obesity effect. These findings support integration of weight management into routine care for rheumatoid arthritis and improved BMI representation in future trials.

Impact of BMI on response to Janus kinase inhibitors in rheumatoid arthritis: an individual patient data meta-analysis of randomised controlled trials

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