A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study

Abstract

BackgroundCT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®). The aim of this study was to compare the 54-week efficacy, immunogenicity, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of CT-P13 and RP in patients with active rheumatoid arthritis (RA).MethodsIn this multinational phase III double-blind study, patients with active RA and an inadequate response to methotrexate (MTX) were randomized (1:1) to receive CT-P13 (3 mg/kg) or RP (3 mg/kg) at weeks 0, 2, 6 and then every 8 weeks to week 54 in combination with MTX (12.5–25 mg/week). Efficacy endpoints included American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates, Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), European League Against Rheumatism (EULAR) response rates, patient-reported outcomes and joint damage progression. Immunogenicity, safety and PK/PD outcomes were also assessed.ResultsOf 606 randomized patients, 455 (CT-P13 233, RP 222) were treated up to week 54. At week 54, ACR20 response rate was highly similar between groups (CT-P13 74.7 %, RP 71.3 %). ACR50 and ACR70 response rates were also comparable between groups (CT-P13 43.6 % and 21.3 %, respectively; RP 43.1 % and 19.9 %, respectively). DAS28, SDAI and CDAI decreased from baseline to week 54 to a similar extent with CT-P13 and RP. Radiographic progression measured by Sharp scores as modified by van der Heijde was also comparable. With both treatments, patient assessments of pain, disease activity and physical ability, as well as mean scores on the Medical Outcomes Study Short Form Health Survey (SF-36), improved markedly at week 14 and remained stable thereafter up to week 54. The proportion of patients positive for antidrug antibodies at week 54 was similar between the two groups: 41.1 % and 36.0 % with CT-P13 and RP, respectively. CT-P13 was well tolerated and had a similar safety profile to RP. PK/PD results were also comparable between CT-P13 and RP.ConclusionsCT-P13 and RP were comparable in terms of efficacy (including radiographic progression), immunogenicity and PK/PD up to week 54. The safety profile of CT-P13 was also similar to that of RP.Trial registrationClinicalTrials.gov identifier: NCT01217086. Registered 4 Oct 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-0981-6) contains supplementary material, which is available to authorized users.

Evaluation of the Cross-reactivity of Antidrug Antibodies to CT-P13 and Infliximab Reference Product (Remicade): An Analysis Using Immunoassays Tagged with Both Agents

“…Informed consent was obtained from all individual participants included in the study (please see [16, 18] for details). This article does not contain any studies with animals performed by any of the authors.…”

Patients with Rheumatoid Arthritis Identified as Potentially Suitable for Biosimilar Infliximabin Europe

“…Clinical evidence is evolving in favor of switching patients from infliximab-biologic to its biosimilar [15][16][17][18]. In this context, patients currently on infliximab-biologic could all be considered for biosimilar-infliximab.…”

Clinical development of biologicals and biosimilars - safety concerns

“…In particular, Celltrion performed a randomized, double-blind, multicenter, parallel-group, phase I study to compare the pharmacokinetics, efficacy, and safety of CT-P13 and Remicade in 250 patients with ankylosing spondylitis (PLANETAS study) [9,10]. The positive results prompted Celltrion to run another randomized, double-blind, multicenter, parallel-group, phase III study to demonstrate equivalence in efficacy and safety of CT-P13 compared with Remicade when coadministered with methotrexate in 606 patients with active rheumatoid arthritis (PLANETRA study) [11,12]. Again, the results showed no clinically meaningful differences regarding the efficacy, safety, and pharmacokinetic profile, between CT-P13 and Remicade.…”