title: Efficacy, safety and pharmacokinetics of biosimilars of anti-tumor necrosis factor-α agents in rheumatic diseases; A systematic review and meta-analysis.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, USA.
authors.forename: Yuga
authors.initials: Y
authors.lastname: Komaki
authors.affiliation: Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, USA.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, USA.
authors.forename: Fukiko
authors.initials: F
authors.lastname: Komaki
authors.affiliation: Department of Internal Medicine, University of Nevada, Reno, USA.
authors.forename: Praneeth
authors.initials: P
authors.lastname: Kudaravalli
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, USA.
authors.forename: Dejan
authors.initials: D
authors.lastname: Micic
authors.affiliation: Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Ido
authors.affiliation: Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, USA. Electronic address: asakurab@medicine.bsd.uchicago.edu.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakuraba
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D059451:Biosimilar Pharmaceuticals; D016017:Odds Ratio; D012216:Rheumatic Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D059451:Biosimilar Pharmaceuticals; D014409:Tumor Necrosis Factor-alpha
keywords: Anti-TNF-α; Biosimilar; Immune mediated disease; Meta-analysis; Systematic review