Comparison of immunogenicity test methods used in clinical studies of infliximab and its biosimilar (CT-P13)

Abstract

Anti-drug antibodies against biologic drugs affect efficacy and safety; therefore, it is important to use appropriate assays for immunogenicity testing in clinical studies. This review describes the electrochemiluminescent (ECL) immunoassay, ELISA, radioimmunoassay, and homogeneous mobility shift assay. The characteristics of ECL, used to assess immunogenicity in comparison trials of CT-P13 (Remsima^®, Inflectra^®) versus its reference medicinal product, infliximab (Remicade^®), are also compared with the other assays, based on published literature. These comparisons show that ECL is more sensitive than ELISA, radioimmunoassay, and homogeneous mobility shift assay, and less affected by drug interference than ELISA. Similar immunogenicity was observed for CT-P13 and reference medicinal product using ECL, demonstrating the reliability of this method to assess immunogenicity in comparative studies.

Keywords:

• analytic methods
• anti-drug antibodies
• biosimilar
• CT-P13
• electrochemiluminescent assay
• ELISA
• homogeneous mobility shift assay
• immunoassays
• infliximab
• radioimmunoassay

Acknowledgements

Editorial support (writing assistance, assembling tables and figures, collating author comments, grammatical editing, and referencing) was provided by Mark O’Connor (Aspire Scientific Limited, Bollington, UK) and was funded by Celltrion Healthcare Co., Ltd (Incheon, Republic of Korea).

Financial & competing interests disclosure

JS Kim, SH Kim, BO Kwon and SS Hong are employees of Celltrion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The advent of biosimilars has the potential to reduce the cost of treatment and may increase the number of patients who can receive therapies to improve symptoms and quality of life. However, it is important that a biosimilar is comparable to its reference medicinal product (RMP) in terms of immunogenicity profiles, pharmacokinetics, efficacy, and safety.

• CT-P13 is the first biosimilar monoclonal antibody to be authorized for use in the EU. The Programme evaLuating the Autoimmune disease iNvEstigational drug CT-P13 in RA patients (PLANETRA) and Programme evaLuating the Autoimmune disease iNvEstigational drug CT-P13 in AS patients (PLANETAS) clinical trials showed that CT-P13 is highly comparable to its infliximab RMP.

• A key concern with infliximab is the development of anti-drug antibodies (ADAs), which can negatively affect efficacy and safety of the drug. Therefore, it is crucial to compare the development of ADAs between CT-P13 and infliximab RMP using an appropriate assay method.

• The available assays include electrochemiluminescent (ECL) immunoassay, ELISA, radioimmunoassay, and homogeneous mobility shift assay.

• ECL was used in the PLANETRA and PLANETAS clinical trials, and showed similar ADA rates between CT-P13 and RMP (PLANETRA: 48 and 48%, respectively; PLANETAS: 27 and 23%, respectively).

• Comparison of literature-reported values appeared to show that ECL is more sensitive than ELISA, radioimmunoassay, and homogeneous mobility shift assay, and less affected by drug interference than ELISA, with the caveat that patient and study heterogeneity limit cross-study comparisons.

• ADA rates with infliximab RMP were higher for ECL than ELISA in some, but not all, studies, a finding likely related to the better sensitivity and drug tolerance of ECL. Further research directly comparing ADA detection methods is warranted.

• Overall, these results support use of ECL as a reliable ADA assay method to compare infliximab formulations.

Notes