Efficacy and Safety of Switching from Innovator Rituximab to Biosimilar CT-P10 Compared with Continued Treatment with CT-P10: Results of a 56-Week Open-Label Study in Patients with Rheumatoid Arthritis

Abstract

Background: CT-P10 is a biosimilar candidate of innovator rituximab (RTX) that demonstrated a comparable clinical profile to RTX in a phase I randomized controlled trial (RCT) in rheumatoid arthritis (RA) (ClinicalTrials.gov identifier: NCT01534884).

Objective: This open-label extension (OLE) study (NCT01873443) compared the efficacy and safety of CT-P10 in patients with RA who received CT-P10 from the outset (i.e., from the start of the RCT and also in the OLE; 'maintenance group') with those who received RTX during the RCT and switched to CT-P10 during the OLE ('switch group').

Methods: Patients who completed the RCT were recruited. Based on the Disease Activity Score using 28 joints (DAS28) and predefined safety criteria, patients could receive up to two courses of CT-P10 during the OLE. Efficacy [DAS28 and European League Against Rheumatism (EULAR) response], safety and immunogenicity were assessed.

Results: Eighty-seven patients were enrolled; 58 and 29 had previously received CT-P10 or RTX, respectively, in the RCT. Of these, 38 (65.5%) and 20 (69.0%) were treated with CT-P10 in the OLE and therefore comprised the maintenance and switch groups, respectively. The mean change in DAS28-erythrocyte sedimentation rate (ESR) from baseline (week 0 of RCT) at week 24 of the first OLE treatment course in the maintenance and switch groups was -2.7 and -2.4, respectively. The proportion of patients with good/moderate EULAR responses was also comparable between groups. Antidrug antibodies were detected in 13.2 and 15.0% of patients in the maintenance and switch groups, respectively, at week 24 of the first OLE course. CT-P10 treatment was well-tolerated when administered for up to 2 years or after switching from RTX.

Conclusion: In this study population, comparable efficacy and safety profiles were observed in patients who switched from RTX to CT-P10 and those maintained on CT-P10 throughout treatment.

Conflict of interest statement

Funding

The study was sponsored by CELLTRION, Inc. (Incheon, Republic of Korea). The funding body contributed to the design of the study, the collection, analysis, and interpretation of data, and the review of drafts and final version of the manuscript.

Conflict of interest

WP received consulting fees during the conduct of the study and grants outside the submitted work from CELLTRION. PH and SR received grants form CELLTRION for conducting the clinical trial. MJL received grants from CELLTRION during the conduct of the study. SJL is an employee of, and holds stock options in, CELLTRION. SYL and SHK are employees of CELLTRION. DHY is a scientific consultant and on the speaker’s bureau of CELLTRION and has received research grants not related to this clinical study. C-HS, SCS, FFCM, SJ, FGM-R, PW, EYL, PS, VK, LM, MS, and J-YC declare no conflicts of interest.

Ethical approval

This study was performed according to the principles of the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice guidelines. Study protocols and consent forms were approved by the relevant independent ethics committees. The following ethical bodies approved the study in the centers involved—Brazil: Comitê de Ética em Pesquisa da Associação de Assistência à Criança Deficiente; Comitê de Ética em Pesquisa do Hospital de Clínicas da Universidade Federal do Paraná; Republic of Korea: IRB of IN-HA University Hospital; SNUMC/SNUH IRB; IRB of Daegu Catholic University Medical Center; Mexico: Comité de Ética ICLE SC; Comités de Ética e Investigación en Salud Centro de Especialidades Médicas del Sureste SA de CV; Comité de Ética e Investigación para Estudios en Humanos del “Hospital Médica Sur” S.A.B de C.V.; Comité Bioetico para la Investigación Clínica S.C; Poland: The Bioethics Committee at the Regional Medical Council of Wielkopolska Medical Chamber; Russia: Council on Ethics, Annex to the Order of the Ministry of Healthcare of the Russian Federation; Spain: Comité Ético de Investigación Clínica de Andalucía; Ukraine: Commission on Ethics Questions of State Institution National Scientific Center.

Informed consent

All patients provided written informed consent to participate in the OLE study.

Figures

Fig. 1

Patient flow (RCT and OLE). aPatients who completed the RCT received one or two courses of treatment. b45 patients completed the RCT but did not enter the OLE; reasons for this were absence of new signed informed consent form (n = 17), delay in timelines for ministry or institutional review board review/approval of the OLE protocol (n = 8), screening failure (n = 11), other (n = 9). cStable disease = DAS28-ESR or DAS28-CRP response had not worsened by ≥20% versus the best response during weeks 16–24 of the previous treatment course. dPatients enrolled in the OLE could receive up to two courses of treatment. However, all patients who completed the OLE received one course with the exception of one patient (in the maintenance group) who received two courses in the OLE. CRP C-reactive protein, DAS28 Disease Activity Score using 28 joints, ESR erythrocyte sedimentation rate, OLE open-label extension, RCT randomized controlled trial, RTX innovator rituximab

Fig. 2

Mean (standard deviation) change in a DAS28-ESR and b DAS28-CRP from baseline in patients who received CT-P10 during the OLE study (efficacy population). Baseline refers to week 0 of the preceding phase I RCT. aPatients treated with CT-P10 during the preceding phase I RCT and also during the OLE study. bPatients treated with RTX during the preceding phase I RCT and with CT-P10 during the OLE study. One patient was excluded from the efficacy population due to major protocol deviations [non-compliance with the eligibility criteria (received >2 biologic agents prior to start of study) plus received prohibited medication after study commencement]. CRP C-reactive protein, DAS28 Disease Activity Score using 28 joints, ESR erythrocyte sedimentation rate, OLE open-label extension, RCT randomized controlled trial, RTX innovator rituximab

Fig. 3

Proportion of patients achieving a good/moderate EULAR response in patients who received CT-P10 during the OLE study (efficacy population). aPatients treated with CT-P10 during the preceding phase I RCT and also during the OLE study. bPatients treated with RTX during the preceding phase I RCT and with CT-P10 during the OLE study. One patient was excluded from the efficacy population due to major protocol deviations [non-compliance with the eligibility criteria (received >2 biologic agents prior to start of study) plus received prohibited medication after study commencement]. CRP C-reactive protein, ESR erythrocyte sedimentation rate, EULAR European League Against Rheumatism, OLE open-label extension, RCT randomized controlled trial, RTX innovator rituximab