Journal Article

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study

Mikazane, Helena, Lee, Yeon-Ah, Lee, Sang Joon, Kim, HoUng, Lysenko, Grygorii, Gutierrez-Ureña, Sergio, Miranda, Pedro, Kovalenko, Volodymyr, Lim, MieJin, Park, Won, Jeka, Slawomir, Braun, Jürgen, Yoo, Dae Hyun, Hrycaj, Pawel

2013

Overview

Objectives To compare the pharmacokinetics (PK), safety and efficacy of innovator infliximab (INX) and CT-P13, a biosimilar to INX, in patients with active ankylosing spondylitis (AS). Methods Phase 1 randomised, double-blind, multicentre, multinational, parallel-group study. Patients were randomised to receive 5 mg/kg of CT-P13 (n=125) or INX (n=125). Primary endpoints were area under the concentration-time curve (AUC) at steady state and observed maximum steady state serum concentration (Cmax,ss) between weeks 22 and 30. Additional PK, efficacy endpoints, including 20% and 40% improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria (ASAS20 and ASAS40), and safety outcomes were also assessed. Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX. Geometric mean Cmax,ss was 147.0  μg/ml for CT-P13 and 144.8 μg/ml for INX. The ratio of geometric means was 104.5% (90% CI 94% to 116%) for AUC and 101.5% (90% CI 95% to 109%) for Cmax,ss. ASAS20 and ASAS40 responses at week 30 were 70.5% and 51.8% for CT-P13 and 72.4% and 47.4% for INX, respectively. In the CT-P13 and INX groups more than one adverse event occurred in 64.8% and 63.9% of patients, infusion reactions occurred in 3.9% and 4.9%, active tuberculosis occurred in 1.6% and 0.8%, and 27.4% and 22.5% of patients tested positive for anti-drug antibodies, respectively. Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS. CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of INX up to week 30.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited,BMJ Publishing Group
• Subject: Adolescent / Adult / Aged / Antibodies, Monoclonal - adverse effects / Antibodies, Monoclonal - blood / Antibodies, Monoclonal - immunology / Antibodies, Monoclonal - therapeutic use / Antibody Formation / Antirheumatic Agents - adverse effects / Antirheumatic Agents - blood / Antirheumatic Agents - immunology / Antirheumatic Agents - therapeutic use / Autoimmune diseases / Clinical and Epidemiological Research / Clinical trials / Cytotoxicity / Disease / Double-Blind Method / Drug dosages / Female / Humans / Hypotheses / Immunoglobulin G - adverse effects / Immunoglobulin G - blood / Immunoglobulin G - immunology / Immunoglobulin G - therapeutic use / Infliximab / Male / Middle Aged / Pharmaceutical industry / Prospective Studies / Severity of Illness Index / Spondylitis, Ankylosing - blood / Spondylitis, Ankylosing - drug therapy / Spondylitis, Ankylosing - immunology / Treatment Outcome / Tuberculosis / Tumor necrosis factor-TNF / Young Adult