参考:Ann Intern Med2016年11月2日 (水)配信

Chingcuanco F et al. Bioequivalence of Biosimilar Tumor Necrosis Factor-α Inhibitors Compared With Their Reference Biologics: A Systematic Review. Ann Intern Med. 2016 Oct 18;165(8):565-574. doi: 10.7326/M16-0428. Epub 2016 Aug 2. TNF-α阻害薬のバイオシミラーと先発薬の生物学的同等性をシステマティックレビューで検討。第1相試験8件で薬物動態パラメータを比較したところ、バイオシミラーと先発薬の差は同等性マージンの範囲内でした(80-125%)。関節リウマチ患者を対象とした第3相試験5件で検討した臨床反応および有害事象も同等と示唆されました。 【原文を読む】 Annals of Internal Medicine  

Bioequivalence of Biosimilar Tumor Necrosis Factor-α Inhibitors Compared With Their Reference Biologics: A Systematic Review

Francine Chingcuanco, MHS; Jodi B. Segal, MD, MPH; Seoyoung C. Kim, MD, ScD, MSCE; G. Caleb Alexander, MD Article, Author, and Disclosure Information


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, 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)