An Open Label, Non-randomized, Prospective Clinical Trial Evaluating the Immunogenicity of Branded Enoxaparin Versus Biosimilars in Healthy Volunteers

作者：Gomes Marise; Ramacciotti Eduardo; Hoppensteadt Debra; Walenga Jeanine M; Lewis Bruce; Thethi Indermohan; Fareed Jawed^*

来源：Clinical and Applied Thrombosis/Hemostasis, 2011, 17(1): 66-69.

DOI：10.1177/1076029610393332

• immunogenicity
• antibody
• low-molecular-weight heparin
• platelet factor 4
• thrombocytopenia

Introduction: Compositional variations among biosimilar enoxaparin could lead to a differential immunogenic response between these preparations. Methods: Enoxaparin (Clexane, n = 110) and a biosimilar version (Cutenox, n = 110) were administered to healthy volunteers in Brazil, 40 mg subcutaneous (SQ), daily, for 10 days. Blood was collected at baseline, days 1 and 10, and analyzed for antiheparin/PF4 antibody (AHPF4 antibodies) titers and subtypes by enzyme-linked-immunosorbent serologic assay (ELISA). Results: Low-molecular-weight heparin (LMWH) treatment resulted in AHPF4 antibodies generation, with differences on day 10 (P < .05). Antibody subtyping (immunoglobulin [Ig] G, IgA, IgM) demonstrated different profiles between LMWH with statistical significance for IgG (Clexane 10 = 0.21 +/- 0.06, Cutenox 10 = 0.28 +/- 0.10, P < .0001) and IgA (Clexane 10 = 0.15 +/- 0.02, versus Cutenox 10 = 0.13 +/- 0.02, P < .0001) on day 10, with a significant drug effect (P < .0001) and significant time by drug interaction (P = .0009). All antibody titers were stated in terms of optical density (OD) units. Conclusion: LMWHs immunogenic potential varies to generate AHPF4 antibodies and subtypes and cross-reactivity with preformed antibodies. Such parameters may be useful in defining the biosimilar LMWHs bioequivalence. Future studies evaluating the immunogenicity of biosimilar drugs are warranted.

• 出版日期2011-2