Impact of BMI on response to Janus kinase inhibitors in rheumatoid arthritis: an individual patient data meta-analysis of randomised controlled trials
Authors' conclusion
Higher BMI was associated with poorer response and a reduced treatment benefit with JAK inhibitors, with obesity acting as an effect modifier.
Study context
- Population
- Adults with RA in phase 3 RCTs of tofacitinib, baricitinib or upadacitinib vs placebo or active comparator; median BMI 26.8 kg/m²
- Participants
- 11,883 adults16 trials
- Comparison
- BMI categories vs healthy weight, in patients treated with JAKi
- Outcome
- Co-primary: ACR20 response and DAS28-CRP
- Follow-up
- Trial-defined primary efficacy timepoint
Methodological detailsone-stage mixed-effects models, validated using two-stage IPD meta-analysis, phase 3 RCTs, Filgotinib trials excluded due to insufficient variables, Overall risk of bias in individual studies low (Cochrane RoB 2)
- One-stage mixed-effects models
- Validated using two-stage IPD meta-analysis
- Phase 3 RCTs
- Filgotinib trials excluded due to insufficient variables
- Overall risk of bias in individual studies low (Cochrane RoB 2)
Pooled result
As reported in the abstract
ACR20 response, adjusted RR vs healthy weight
Each group vs healthy weightAdjusted relative risk (95% CI)
Overweight
0.94(0.91–0.98)
Class 1 obesity
0.92(0.89–0.96)
Class 2 obesity
0.88(0.81–0.96)
Class 3 obesity
0.78(0.71–0.85)
Further pooled results
| Outcome | Adjusted mean difference (95% CI) | |
|---|---|---|
| Co-primary: DAS28-CRP, adjusted MD vs healthy weight · trial-defined primary efficacy timepointOverweightvs Healthy weight | 0.14 (0.06–0.22) | |
| Co-primary: DAS28-CRP, adjusted MD vs healthy weight · trial-defined primary efficacy timepointClass 1 obesityvs Healthy weight | 0.21 (0.12–0.31) | |
| Co-primary: DAS28-CRP, adjusted MD vs healthy weight · trial-defined primary efficacy timepointClass 2 obesityvs Healthy weight | 0.30 (0.16–0.44) | |
| Co-primary: DAS28-CRP, adjusted MD vs healthy weight · trial-defined primary efficacy timepointClass 3 obesityvs Healthy weight | 0.54 (0.37–0.70) | |
| −0.500.51Difference (linear scale) |
BMI gradient in placebo group
- No corresponding BMI gradient was observed in the placebo group
Original publication
Impact of BMI on response to Janus kinase inhibitors in rheumatoid arthritis: an individual patient data meta-analysis of randomised controlled trials. Lancet Rheumatol. Published 3 August 2026. doi:10.
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