Association of concomitant metformin use and remission outcomes in rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs: a retrospective multicohort analysis.

Aims: It has been suggested that metformin inhibits osteoclast activation through downregulation of the receptor activator of nuclear factor κB (NF- κB) expression and by regulating T-cell differentiation via suppression of the mTOR pathway; both of these pathways are involved in the pathophysiology of rheumatoid arthritis (RA). Therefore, it has been hypothesised that metformin may modulate the response to DMARDs in the treatment of RA. The aim of this study was to examine the association between concomitant metformin use at baseline and remission in RA patients treated with conventional synthetic or biological disease-modifying antirheumatic drugs (csDMARDs or bDMARDs, respectively).

Methods: Data were pooled from 5 clinical trials of RA patients assigned to treatment with the bDMARD, tocilizumab, or csDMARDs. Remission outcomes were set according to the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) and a remission ‘event’ was defined by the time from randomization to the time of first remission. Cox proportional analysis was used to assess the association between concomitant metformin use and remission. The hazard ratio (HR) is interpreted herein as the likely proportion of patients achieving clinical remission.

Results: The 5 cohorts consisted of a total of 5502 patients treated with tocilizumab (4126 [75%]) or csDMARDs (1376 [25%]), 236 (4.3%) of whom were using metformin concomitantly. In the pooled analysis, there was no statistically significant association between metformin use and remission (average adjusted HR 1.11 [95% CI 0.80-1.56, P-value = 0.533] and 1.16 [0.85-1.59, P-value = 0.343] using SDAI- and CDAI-based remission criteria, respectively.

Conclusion: Our results suggest that there is no difference in the likelihood of remission according to concomitant use of metformin. Despite the large number of patients included in these trials, relatively few were taking metformin, so a larger study is needed to elucidate the effects of metformin in treatment outcomes in RA patients.