A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis.

Autor: Smolen JS; Department of Rheumatology, Medical University of Vienna, Vienna, Austria., Cohen SB; Metroplex Clinical Research, Dallas, Texas, USA., Tony HP; Department of Internal Medicine, Rheumatology/Clinical Immunology, University of Wuerzburg, Wuerzburg, Germany., Scheinberg M; Department of Rheumatology, Hospital Israelite Albert Einstein, Sao Paulo, Brazil., Kivitz A; Altoona Center for Clinical Research, Duncansville, Pennsylvania, USA., Balanescu A; Research Center of Rheumatic Diseases, St Mary Hospital, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania., Gomez-Reino J; University Clinic of Santiago, Santiago, Spain., Cen L; Department of Statistics, Sandoz, a Novartis Division, Princeton, New Jersey, USA., Zhu P; Sandoz, a Novartis Division, Clinical Pharmacology, Princeton, New Jersey, USA., Shisha T; Sandoz, a Novartis Division, Hexal AG, Clinical Development, Holzkirchen, Germany.
Jazyk: angličtina
Zdroj: Annals of the rheumatic diseases [Ann Rheum Dis] 2017 Sep; Vol. 76 (9), pp. 1598-1602. Date of Electronic Publication: 2017 Jun 21.
DOI: 10.1136/annrheumdis-2017-211281
Abstrakt: Objectives: The aim of this report is to demonstrate pharmacokinetic (PK) and pharmacodynamic (PD) equivalence as well as similar efficacy, safety and immunogenicity between GP2013, a biosimilar rituximab, and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate response or intolerance to tumour necrosis factor inhibitor (TNFi) treatment.
Methods: In this multinational, randomised, double-blind, parallel-group study, 312 patients with active disease despite prior TNFi therapy were randomised to receive GP2013 or either the EU (RTX-EU) or the US (RTX-US) reference product, along with methotrexate (MTX) and folic acid. The primary endpoint was the area under the serum concentration-time curve from study drug infusion to infinity (AUC 0-inf ). Additional PK and PD parameters, along with efficacy, immunogenicity and safety outcomes were also assessed up to week 24.
Results: The 90% CI of the geometric mean ratio of the AUCs were within the bioequivalence limits of 80% to 125% for all three comparisons; GP2013 versus RTX-EU: 1.106 (90% CI 1.010 to 1.210); GP2013 versus RTX-US: 1.012 (90% CI 0.925 to 1.108); and RTX-EU versus RTX-US: 1.093 (90% CI 0.989 to 1.208). Three-way PD equivalence of B cell depletion was also demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX.
Conclusions: Three-way PK/PD equivalence of GP2013, RTX-EU and RTX-US was demonstrated. Efficacy, safety and immunogenicity profiles were similar between GP2013 and RTX.
Trial Registration Number: NCT01274182; Results.
Competing Interests: Competing interests: PZ, LC and TS are employees of Sandoz/Hexal. JSS, HPT, AK, AB, JG-R and MS received investigator fees from Sandoz, a Novartis Division.
(© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
Databáze: MEDLINE
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