Impact of Anti-Drug Antibody on Efficacy and Safety over Week 24 in Both CT-P10 and Innovator Rituximab Treatment Groups

초록

Background: CT-P10 is a biosimilar candidate for rituximab. Pharmacokinetic equivalence and similarity of clinical efficacy, safety and immunogenicity had been demonstrated between CT-P10 and Innovator Rituximab (RTX) groups1. The immunogenicity to the biologic monoclonal antibody may affect both patient’s safety and therapeutic efficacy. Until now the presence of human anti-chimeric antibodies (HACA) to rituximab was known not to change the clinical efficacy and safety of rituximab. The purpose of this analysis was to demonstrate the impact of anti drug antibody (ADA) on efficacy and safety of CT P10 and RTX in patients with rheumatoid arthritis (RA) over week 24. Methods: A total of 154 RA patients were randomized 2:1 to receive 2 infusions (1000 mg, 2 week interval) of either CT-P10 (n=103) or RTX (n=51), and efficacy, safety and immunogenicity were assessed during the study. Electrochemilumencent (ECL) assay was used to assess immunogenicity in this study since this assay is about 10 times more sensitive than the enzyme-linked immuno sorbent assay (ELISA) which was used in the historical rituximab trials. The impact of ADA on efficacy and safety in both treatment groups was evaluated at week 24, when drug concentration was low enough not to interfere with the analysis. Results: The proportion of patients who developed ADA at week 24 was exactly same (17.6% each) in both CT-P10 and RTX treatment groups. Similar proportion of patients achieved ACR20 and the European League Against Rheumatism (EULAR-CRP and -ESR) responses between after the CT-P10 and RTX treatment groups in both ADA positive and negative subgroups (Table 1). The interference of the ADA on the clinical response was not significant in both treatment groups. The safety profiles of CT-P10 were generally comparable to those of RTX in both ADA (+) and (-) subgroups. The proportion of patients with adverse event (AE) were 55.6% and 49.4% for CT-P10-ADA (+) and (-) subgroups and 88.9% and 67.6%