Thus, B cells are an important and appropriate target for the treatment of RA, as confirmed by the efficacy of rituximab since its approval in 2006. The pathophysiology of RA is unknown, although it is thought to involve activation of an innate immune response, including antigen presentation and production of autoantibodies and cytokines by B cells, and involvement of other key effector cells and inflammatory modulators 7. It is indicated for non‐Hodgkin's lymphoma, chronic lymphocytic leukaemia (in combination with chemotherapy), rheumatoid arthritis (RA in combination with methotrexate) and granulomatosis with polyangiitis and microscopic polyangiitis (in combination with glucocorticoids) 5, 6. Rituximab is a genetically engineered chimeric murine/human monoclonal immunoglobulin (Ig) G1κ antibody directed against the CD20 antigen of B cells 5, 6.
Regulatory decisions for approval are based on the totality of the evidence generated from a stepwise approach that generally includes analytical, clinical pharmacokinetic (PK), and efficacy and safety studies intended to support the demonstration of biosimilarity 1, 2, 3, 4. Biologics are large, structurally complex molecules even minor changes in the manufacturing process could produce differences that can affect the safety, immunogenicity and potency of the molecule 3, 4. Biosimilars are expected to be an essential component in enhancing patient access to these important, often lifesaving biologic products. The term ‘biosimilar’ refers to a biologic product developed to be highly similar to an existing licensed or approved biologic product 1, 2, 3, 4. No clinically meaningful differences in adverse events were identified. None of the ADA‐positive samples was positive for neutralizing activity. 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. All treatments resulted in a rapid and profound reduction in CD19+ B cells and sustained profound B cell suppression up to week 25. The 90% confidence intervals of test‐to‐reference ratios for C max, AUC T, AUC 0–∞ and AUC 2‐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. PF‐05280586, rituximab‐EU and rituximab‐US exhibited similar PK profiles following administration of assigned study drug on days 1 and 15. Of these, 198 met per‐protocol population criteria for inclusion in the PK data analysis. A total of 220 patients were randomized to receive study treatment as assigned.
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