Background: Biosimilars are of growing clinical, regulatory, and commercial importance.
Purpose: To summarize evidence about the bioequivalence between biosimilar and reference tumor necrosis factor-α (TNF-α) inhibitors.
Data sources: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and LILACS from inception through 13 April 2016 and ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, EU Clinical Trials Register, U.S. Food and Drug Administration, and European Medicines Agency from inception through 30 April 2016.
Study selection: Published English-language studies of any size or design that compared the pharmacokinetics, clinical efficacy, adverse events, or immunogenicity of a biosimilar TNF-α inhibitor with a reference biologic in humans.
Data extraction: Two reviewers independently screened titles and abstracts, extracted data from selected studies, and assessed study quality.
Data synthesis: Of 19 eligible studies, 8 were phase 1 randomized trials, 5 were phase 3 randomized trials, and 6 were observational studies. Most phase 1 trials (n = 7) involved healthy volunteers, phase 3 trials involved patients with rheumatoid arthritis, and observational studies involved those with rheumatoid arthritis or inflammatory bowel disease. All phase 1 trials showed that pharmacokinetic parameters of the biosimilar and respective biologic were within the prespecified equivalence margin of 80% to 125%. Phase 3 trials suggested similar clinical responses and adverse events. Adverse events were usually of mild to moderate severity. Two cross-sectional observational studies showed cross-reactivity between products, whereas 4 cohort studies of patients switched from reference to biosimilar products suggested similar efficacy and safety outcomes.
Limitation: Possible publication bias, small sample sizes of many studies, and lack of published studies for several biosimilars.
Conclusion: Preliminary evidence supports the biosimilarity and interchangeability of biosimilar and reference TNF-α inhibitors.
Primary funding source: Johns Hopkins Center of Excellence in Regulatory Science and Innovation. (PROSPERO: CRD42015025262).