Extension Study of PF-05280586, a Potential Rituximab Biosimilar, Versus Rituximab in Subjects With Active Rheumatoid Arthritis

Abstract

Objective: This extension study provided continued treatment to subjects with active rheumatoid arthritis who had participated for ≥16 weeks in a pharmacokinetic similarity study of PF-05280586 (potential rituximab biosimilar). Objectives were to evaluate overall pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of PF-05280586 after transition from rituximab reference products to PF-05280586, and follow-up of biomarker and efficacy assessments.

Methods: Subjects were offered ≤3 additional courses of treatment of PF-05280586, with or without a single transition from rituximab in Europe (rituximab-EU; MabThera) or the US (rituximab-US; Rituxan) to PF-05280586. Each course comprised 2 intravenous infusions (1,000 mg on days 1 and 15, separated by 24 weeks [± 8 weeks]).

Results: Of 220 subjects in the parent study, 185 were randomized and included in this study. There were no notable differences in drug concentrations between groups or across courses, with little variation in depletion of CD19+ B cells between groups, and no apparent relationship between infusion-related reactions and antidrug antibodies with or without single transition from rituximab reference products to PF-05280586. Long-term safety and tolerability of PF-05280586 was acceptable in all groups for up to 96 weeks, with a low incidence of treatment-emergent adverse events independent of single drug transition. The percentage of subjects with a low disease activity score and disease activity score remission was similar across groups for all time points, and responses were sustained until end of study.

Conclusion: This study demonstrated acceptable safety, tolerability, and immunogenicity, with or without single transition from rituximab reference products to PF-05280586, without increased immunogenicity on single transition.

Trial registration: ClinicalTrials.gov NCT01643928.

© 2018, Pfizer Inc. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

Figures

Figure 1

Study design. E‐E, E‐EP, E‐EPP = subjects who were randomized to the rituximab‐Europe (EU) cohort in the parent study and then randomized in this study to receive the rituximab‐EU reference product during course 1, followed by the PF‐05280586 investigational product during courses 2 and 3; E‐P, E‐PP, E‐PPP = subjects who were randomized to the rituximab‐EU cohort in the parent study and then randomized in this study to receive the PF‐05280586 investigational product during courses 1, 2 and 3; U‐P, U‐PP, U‐PPP = subjects who were randomized to rituximab‐US in the parent study and then randomized in this study to receive the PF‐05280586 investigational product during courses 1, 2 and 3; U‐U, U‐UP, U‐UPP = subjects who were randomized to rituximab‐US in the parent study and then randomized in this study to receive the US reference product during course 1, followed by the PF‐05280586 investigational product during courses 2 and 3; P‐P, P‐PP, P‐PPP = subjects who were randomized to PF‐05280586 in the parent study and continued receiving the PF‐05280586 investigational product in this study during courses 1, 2 and 3; MTX = methotrexate.

Figure 2

A, Low Disease Activity Score (DAS; ≤3.2) rate by treatment sequence and visit (modified intent‐to‐treat population [mITT]); n = proportion of subjects with low DAS (≤3.2) for each treatment sequence and visit. B, DAS remission (<2.6) rate by treatment sequence and visit (mITT population); n = proportion of subjects with DAS remission (<2.6) for each treatment sequence and visit. N = total number of subjects receiving treatment in each course/week. See Figure 1 for randomized study group descriptions.