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

초록

Introduction: The aim of the study was 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 (AUC(0-inf), C-max, and AUC(0-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; I-2 = 0%) or ACR20 response rates (RR 1.03; 95% CI: 0.96-1.10; I-2 = 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 AUC(0-inf), 101.4% (98.5-104.4%) for C-max, and 102.3% (97.8-106.9%) for AUC(0-last); all pooled CIs lay entirely within the 80-125% regulatory acceptance range (I-2 <= 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.

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