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.