Tocilizumab Biosimilars Versus Reference Tocilizumab in Rheumatoid Arthritis: A Meta-Analysis of Pharmacokinetic Biosimilarity, Efficacy, Safety, and Immunogenicity

Introduction: To systematically evaluate the efficacy, safety, immunogenicity, and pharmacokinetics (PK) of tocilizumab biosimilars compared to reference tocilizumab (r-TCZ) in patients with rheumatoid arthritis (RA) and healthy volunteers. Methods: We searched PubMed, Embase, and Cochrane CENTRAL for phase I and III randomized controlled trials (RCTs) comparing tocilizumab biosimilars vs. r-TCZ. Primary outcomes included change from baseline in DAS28-ESR, ACR20/50/70 response rates, adverse events (AEs), serious AEs (SAEs), anti-drug antibody (ADA) positivity, and PK parameters (AUC0−inf, Cmax, and AUC0−last). Random-effects meta-analyses were performed using mean difference (MD), risk ratio (RR), and geometric mean ratio (GMR) with 95% or 90% confidence intervals (CIs). This systematic review and meta-analysis have been registered in PROSPERO (CRD420251270353). Results: Eight studies met the inclusion criteria, comprising 3 phase III RCTs (n=1,696 RA patients) and 5 phase I RCTs (n=1,363 healthy volunteers), for a total of 3,059 participants. In RA patients, biosimilars demonstrated equivalent efficacy to r-TCZ at week 24, with no significant differences in DAS28-ESR change (MD –0.06; 95% CI –0.19 to 0.06; I²=0%) or ACR20 response rates (RR 1.03; 95% CI 0.96–1.10; I²=0). Results for ACR50 and ACR70 were similarly balanced. Safety profiles were comparable (any AE: RR 1.01; 95% CI 0.94–1.08), as was immunogenicity (ADA positivity: RR 1.28; 95% CI 0.99–1.65). In healthy volunteers, PK biosimilarity was confirmed across intravenous and subcutaneous routes with pooled GMRs (90% CI) of 104.5% (101.2–107.9%) for AUC0−inf, 101.4% (98.5–104.4%) for Cmax, and 102.3% (97.8–106.9%) for AUC0−last; all pooled CIs lay entirely within the 80–125% regulatory acceptance range (I²≤35). Conclusion: Tocilizumab biosimilars exhibit therapeutic similarity in RA patients and pharmacokinetic biosimilarity in healthy volunteers compared to r-TCZ, with comparable safety and immunogenicity, supporting their use as credible, cost-effective alternatives in clinical practice.