Efficacy and Safety of Tocilizumab Biosimilars Compared to Reference Tocilizumab in the Treatment of Rheumatoid Arthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

INTRODUCTION: Tocilizumab biosimilars offer an innovative therapeutic option for pa-tients with rheumatoid arthritis (RA); however, their safety and efficacy compared with the refer-ence product remain undefined. This systematic review and meta-analysis aim to synthesize data from all randomized clinical trials (RCTs) comparing the efficacy and safety of tocilizumab bio-similars with reference tocilizumab for RA treatment. METHODS: Following PRISMA guidelines, we searched PubMed, the Cochrane Library, and Web of Science up to March 2026. We included RCTs comparing biosimilars of tocilizumab to refer-ence tocilizumab in adult RA patients. Primary efficacy outcomes included ACR20 response and DAS28-ESR; secondary outcomes were ACR50/70, DAS28-CRP, and safety outcomes. RESULTS: Four Phase 3 double-blind RCTs enrolling 2160 patients were included in the analysis. No statistically significant differences were found between biosimilars and reference tocilizumab for ACR20, ACR50, or ACR70 DAS28-CRP responses at 12, 24 weeks, and approximately 1 year. Similarly, no difference was observed in DAS28-ESR change from baseline at 12 (MD, -0.07; P = 0.26) or 24 weeks (MD, -0.04; P = 0.60). However, at approximately 1 year (48-52 weeks), biosimilars showed a statistically significantly greater reduction in DAS28-ESR (MD -0.24, 95% CI: -0.44 to -0.05; P = 0.01) but did not reach the minimal clinically important differ-ence (MCID). Safety profiles were comparable, with no significant differences in safety out-comes. DISCUSSION: Our results indicate that tocilizumab biosimilars are therapeutically equivalent to the reference product in terms of clinical response and safety. However, a primary limitation of this meta-analysis is the small number of included RCTs. Future research should prioritize long-term surveillance and cost-effectiveness analysis in diverse settings to facilitate widespread clinical adoption and ensure sustained patient safety. CONCLUSION: Our meta-analysis shows that tocilizumab biosimilars have efficacy and safety pro-files equivalent to those of reference tocilizumab for the treatment of RA. These findings support the use of biosimilars as an effective therapeutic alternative.