What drives the comparative effectiveness of biologics vs methotrexate in rheumatoid arthritis? Meta-regression and graphical inspection of suspected clinical factors

OBJECTIVE: The aim of this study was to explore which clinical factors and patient characteristics are associated with the magnitude of comparative efficacy between biologics vs. MTX in RA patients with inadequate response to MTX. METHODS: We included randomized controlled trials assessing the efficacy of a biologic plus MTX vs. MTX alone. We examined several clinical factors and patient characteristics potentially associated with magnitude of response, measured as ACR20 (20% improvement in ACR criteria) and ACR50 (16-26 weeks). We employed meta-regression for formal estimates and statistical significance of effect modification. We produced regression and forest plots to further inspect potential associations. RESULTS: For ACR50, a 1-year increment on the average patient disease duration was statistically significantly associated with a 16% relative increase in the pooled odds ratio (OR) estimate (P = 0.003). A 1-year increment in patient age and a 1 mg/week increment in MTX dose were marginally statistically significantly associated with a 9% (P = 0.056) and 22% (P = 0.092) relative increase in the OR. For ACR20, the average number of swollen and tender joints was marginally statistically associated with a 3% relative decrease. The associations for age and MTX dose appeared to be partly driven by significant negative associations between these two factors and the control group response. CONCLUSION: Our analyses identified key variables associated with the magnitude of comparative effects for ACR outcomes. Our findings provide valuable insights for future trial designs and systematic reviews as well as decision-making and clinical practice.