Efficacy, Safety and Pharmacokinetics of Up to Two Courses of the Rituximab Biosimilar CT-P10 Versus Innovator Rituximab in Patients with Rheumatoid Arthritis: Results up to Week 72 of a Phase I Randomized Controlled Trial

Abstract

BackgroundCT-P10 is a biosimilar of innovator rituximab (RTX), a biological therapy used to treat patients with rheumatoid arthritis (RA) who have responded inadequately to anti-tumor necrosis factor agents.ObjectiveOur objective was to compare the clinical profile of CT-P10 versus RTX in patients with RA who received up to two courses of treatment and were followed for up to 72 weeks.MethodsIn this multicenter double-blind phase I study, patients were randomized 2:1 to receive CT-P10 1000 mg or RTX 1000 mg at weeks 0 and 2. Based on disease activity, patients could receive a second course of treatment between weeks 24 and 48. Efficacy endpoints, including mean change from baseline in Disease Activity Score using 28 joints (DAS28), safety, immunogenicity, pharmacokinetics, and pharmacodynamics were evaluated.ResultsIn total, 154 patients were randomized to CT-P10 or RTX (n = 103 and 51, respectively); 137 (n = 92 and 45) completed the first course of treatment, of whom 83 (n = 60 and 23) were re-treated. Improvements from baseline in all efficacy endpoints were highly similar between the CT-P10 and RTX groups over both treatment courses. At week 24 after the second course, mean change from week 0 of the first course in DAS28 erythrocyte sedimentation rate was −2.47 and −2.04 for CT-P10 and RTX, respectively, (p = 0.1866) and in DAS28 C-reactive protein was −2.32 and −2.00, respectively (p = 0.3268). The proportion of patients positive for antidrug antibodies at week 24 after the second treatment course was 20.0% and 21.7% in the CT-P10 and RTX groups, respectively. The safety profile of CT-P10 was comparable to that of RTX, and pharmacokinetic and pharmacodynamic properties were similar.ConclusionsIn patients with RA, efficacy, safety, and other clinical data were comparable between CT-P10 and RTX after up to two courses of treatment over 72 weeks.(ClinicalTrials.gov identifier NCT01534884).Electronic supplementary materialThe online version of this article (doi:10.1007/s40259-017-0232-7) contains supplementary material, which is available to authorized users.

2017 recommendations of the Brazilian Society of Rheumatology for the pharmacological treatment of rheumatoid arthritis

“…bsDMARDs have been shown to be safe and effective when used as an alternative to boDMARDs (moderate evidence). There were no differences in ACR20 and ACR70 response rates, disease activity (moderate evidence), or severe adverse events of the bsDMARDs adalimumab, etanercept, infliximab, and rituximab compared with their respective boDMARDs [134][135][136][137][138][139][140]. The development of anti-drug antibodies was similar between bsDMARDs and boDMARDs (moderate evidence), and lower for the bsDMARD of etanercept compared with the boDMARD (high evidence) [134].…”

Past, Present, and Future of Rituximab—The World’s First Oncology Monoclonal Antibody Therapy

“…Also known as Truxima™, this is the first biosimilar to be granted marketing authorization by the EU, in 2016 ( 159 ). A phase I and phase III trial of CT-P10 was done to confirm safety, similar PK/PD, and efficacy in RA patients ( 176 ). There were no significant differences between CT-P10 and rituximab, and CT-P10 was also tested in untreated advanced stage FL patients.…”

Scientific rationale for extrapolation of biosimilar data across cancer indications: case study of CT-P10

“…Randomized controlled studies compared the pharmacokinetics (PK), efficacy, safety and immunogenicity of CT-P10 and RTX in patients with RA and advanced FL [10][11][12][13][14][15][16]. Briefly, PK equivalence of CT-P10 and RTX was demonstrated in Phase I and III trials in patients with RA [10,12].…”