A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: The PLANETRA study

Dae Hyun Yoo, Hanyang University
Pawel Hrycaj, Poznan University of Medical Sciences
Pedro Miranda, Centro de Estudios Reumatológicos
Edgar Ramiterre, Brokenshire Memorial Hospital
Mariusz Piotrowski, Reumed
Sergii Shevchuk, Scientific and Research Institute of Invalid Rehabilitation of MoH of Ukraine
Volodymyr Kovalenko, National Science Center Kharkov Institute of Physics and Technology
Nenad Prodanovic, Clinical Center Banja Luka
Mauricio Abello-Banfi, Centro Integral de Reumatologia del Caribe
Sergio Gutierrez-Ureña, Hospital Civil de Guadalajara
Luis Morales-Olazabal, Hospital María Auxiliadora
Michael Tee, De La Salle Medical and Health Sciences Institute
Renato Jimenez, Centro de Estudios Investigaciones Clinicas
Omid Zamani, Rheumazentrum Favoriten
Sang Joon Lee, The University of New Mexico
Ho Ung Kim, Celltrion, Inc.
Won Park, Inha University Hospital
Ulf Müller-Ladner, Justus Liebig University Giessen

Abstract

Objectives To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. Methods Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5-25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. Results At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI -6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28-CRP, ACR-EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX.