Efficacy, safety and pharmacokinetics of biosimilars of anti-tumor necrosis factor-α agents in rheumatic diseases; A systematic review and meta-analysis

• Published in: Journal of autoimmunity Vol. 79; pp. 4 - 16
• Main Authors: Komaki, Yuga, M.D, Yamada, Akihiro, M.D., Ph.D, Komaki, Fukiko, M.D, Kudaravalli, Praneeth, M.D, Micic, Dejan, M.D, Ido, Akio, M.D., Ph.D, Sakuraba, Atsushi, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-05-2017
• Subjects: Allergy and Immunology; Anti-TNF-α; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antirheumatic Agents - pharmacology; Antirheumatic Agents - therapeutic use; Biosimilar; Biosimilar Pharmaceuticals; Immune mediated disease; Meta-analysis; Odds Ratio; Rheumatic Diseases - drug therapy; Rheumatic Diseases - immunology; Rheumatic Diseases - metabolism; Systematic review; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - metabolism; Systematic review; Immune mediated disease; Biosimilar; Anti-TNF-α; Meta-analysis
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2017.02.003

Abstract Objective To evaluate the efficacy and safety of biosimilars of anti-tumor necrosis factor (TNF)-α agents compared to their reference agents in immune mediated diseases. Methods Electronic databases were searched for randomized controlled trials (RCTs) assessing the efficacy and safety of biosimilars of anti-TNF-α agents compared to their reference agents in patients with various immune mediated diseases. The outcomes were the rates of clinical response and adverse events among patients treated with biosimilars compared to their reference agents. Additionally, occurrence of anti-drug antibodies with the use of biosimilars was compared to the reference agents. Results Nine studies reporting outcomes in 3291 patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) were identified (5 infliximab, 2 adalimumab, and 2 etanercept). No RCTs in other diseases were found. Biosimilars of infliximab showed similar rates of clinical response compared to the reference agent in RA and AS. Frequency of anti-drug antibody and adverse events were similar except for a slightly, but significantly, higher risk of upper respiratory tract infections with biosimilar (RR 1.54, P  = 0.047, 95% confidence interval (CI) = 1.01–2.37). Biosimilar of adalimumab showed no differences among any outcomes compared to the reference agent. Biosimilars of etanercept showed no differences for clinical response and frequency of adverse events, but showed a significantly lower rate of anti-drug antibodies at 24–30 weeks (RR 0.05, P <0.0001%, 95% CI = 0.01–0.21). Conclusion In the present study, biosimilars of anti-TNF-α agents had an overall comparable efficacy and safety profile compared to their reference agents in RA and AS supporting their use for these conditions.