Cohen, S, Emery, P, Greenwald, M et al. (8 more authors) (2016) A phase I pharmacokinetics trial comparing PF-05280586 (a potential biosimilar) and rituximab in patients with active rheumatoid arthritis. British Journal of Clinical Pharmacology, 82 (1). pp. 129-138. ISSN 0306-5251
Abstract
Aims: Pharmacokinetic (PK) similarity was assessed among PF‐05280586 (a proposed biosimilar) vs. rituximab sourced from the European Union (rituximab‐EU) and the United States (rituximab‐US). Pharmacodynamics (PD), overall safety and immunogenicity were also evaluated.
Methods: Patients with active rheumatoid arthritis on a background of methotrexate and inadequate response to one or more tumour necrosis factor antagonist therapies were randomized to intravenous PF‐05280586, rituximab‐EU or rituximab‐US 1000 mg doses on study days 1 and 15.
Results: A total of 220 patients were randomized to receive study treatment as assigned. Of these, 198 met per‐protocol population criteria for inclusion in the PK data analysis. PF‐05280586, rituximab‐EU and rituximab‐US exhibited similar PK profiles following administration of assigned study drug on days 1 and 15. The 90% confidence intervals of test‐to‐reference ratios for Cmax, AUCT, AUC0–∞ and AUC2‐week were within the bioequivalence margin of 80.00–125.00% for comparisons of PF‐05280586 with rituximab‐EU, PF‐05280586 with rituximab‐US, and rituximab‐EU with rituximab‐US. All treatments resulted in a rapid and profound reduction in CD19+ B cells and sustained profound B cell suppression up to week 25. The incidence of antidrug antibody (ADA) response (n = 7, 10 and 9 for PF‐05280586, rituximab‐EU and rituximab‐US, respectively), time to ADA emergence and ADA titres were similar across treatments. None of the ADA‐positive samples was positive for neutralizing activity. No clinically meaningful differences in adverse events were identified.
Conclusions: The study demonstrated PK similarity among PF‐05280586, rituximab‐EU and rituximab‐US. In addition, all treatments showed comparable CD19+ B cell depletion PD responses, as well as safety and immunogenicity profiles.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2016, Pfizer Inc. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmocological Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License [https://creativecommons.org/licenses/by-nc-nd/4.0/], which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
Keywords: | biosimilar; CD19+ B cell counts; immunogenicity; pharmacokinetics; rituximab; safety |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Aug 2018 11:25 |
Last Modified: | 10 Aug 2018 11:25 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/bcp.12916 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:134228 |