Background/Purpose 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 after the CT-P10 and RTX treatment in both ADA (+) and (-) 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% for RTX-ADA (+) and (-) subgroups, respectively. Serious AE was reported in 11.1% and 15.6% in the CT-P10-ADA (+) and (-) subgroups and 22.2% and 16.2% in the RTX-ADA (+) and (-) subgroups, respectively. The proportion of patients with AE due to infections and infusion related reactions was also similar between the treatment groups in ADA (+) and (-) subgroups.
Conclusion The development of ADA did not affect clinical response or safety profiles in RA patients treated with CT‑P10 or RTX, and the magnitude of impact of ADA was similar in both treatment groups. These results confirmed the comparability of CT-P10 to those of RTX in efficacy and safety over 24 weeks regardless of the immunogenic reaction.