Expanding the clinical utility of reporter gene assay to infliximab biosimilars

Abstract

Objective: Infliximab and its biosimilars are approved for the treatment of inflammatory diseases. Monitoring of serum drug and anti-drug antibody levels is essential for managing patients with treatment failure. A reporter gene assay (RGA), previously developed for infliximab, was validated for the measurement of biosimilars infliximab-dyyb and infliximab-abda, and detection of anti-drug antibodies (ADA).

Method: 65 de-identified residual serum samples from patients receiving infliximab or its biosimilars, were tested. ELISA and cell-based reporter gene assay were performed to measure drug while a bridging ELISA and a modified RGA assay were performed to detect ADA.

Results: Analysis of assay analytical parameters showed acceptable linearity (systematic error < 15 %), recovery (82-119 %), precision and reproducibility (coefficient of variation < 15 %) of the RGA assay for measuring biosimilars. Detection of ADA developed against infliximab or biosimilars showed a complete agreement (Cohen's k = 1; 95 % CI = 1.0 to 1.0) between the RGA assays using infliximab, versus infliximab-dyyb, or infliximab-abda as assay reagents.

Conclusions: A functional cell-based reporter gene assay was validated for measuring serum concentrations of infliximab biosimilars and neutralizing antibodies. This study supports the bio- equivalency and cross-immunogenicity of parent drug and biosimilars and offers guidance for management of patients switching therapies between parent drug and biosimilars.

Keywords: Anti-drug antibody; Biosimilar; Infliximab; Infliximab-abda; Infliximab-dyyb; Reporter gene assay; TNF antagonist.