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

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 respo...

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Autores principales: Smolen, Josef S, Cohen, Stanley B, Tony, Hans-Peter, Scheinberg, Morton, Kivitz, Alan, Balanescu, Andra, Gomez-Reino, Juan, Cen, Liyi, Zhu, Peijuan, Shisha, Tamas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Annals of the Rheumatic Diseases 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561377/
https://www.ncbi.nlm.nih.gov/pubmed/28637670
http://dx.doi.org/10.1136/annrheumdis-2017-211281
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author Smolen, Josef S
Cohen, Stanley B
Tony, Hans-Peter
Scheinberg, Morton
Kivitz, Alan
Balanescu, Andra
Gomez-Reino, Juan
Cen, Liyi
Zhu, Peijuan
Shisha, Tamas
author_facet Smolen, Josef S
Cohen, Stanley B
Tony, Hans-Peter
Scheinberg, Morton
Kivitz, Alan
Balanescu, Andra
Gomez-Reino, Juan
Cen, Liyi
Zhu, Peijuan
Shisha, Tamas
author_sort Smolen, Josef S
collection PubMed
description 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.
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spelling pubmed-55613772017-08-28 A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis Smolen, Josef S Cohen, Stanley B Tony, Hans-Peter Scheinberg, Morton Kivitz, Alan Balanescu, Andra Gomez-Reino, Juan Cen, Liyi Zhu, Peijuan Shisha, Tamas Ann Rheum Dis Clinical and Epidemiological Research 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. Annals of the Rheumatic Diseases 2017-09 2017-06-21 /pmc/articles/PMC5561377/ /pubmed/28637670 http://dx.doi.org/10.1136/annrheumdis-2017-211281 Text en © 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. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Clinical and Epidemiological Research
Smolen, Josef S
Cohen, Stanley B
Tony, Hans-Peter
Scheinberg, Morton
Kivitz, Alan
Balanescu, Andra
Gomez-Reino, Juan
Cen, Liyi
Zhu, Peijuan
Shisha, Tamas
A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis
title A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis
title_full A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis
title_fullStr A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis
title_full_unstemmed A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis
title_short A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis
title_sort randomised, double-blind trial to demonstrate bioequivalence of gp2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis
topic Clinical and Epidemiological Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561377/
https://www.ncbi.nlm.nih.gov/pubmed/28637670
http://dx.doi.org/10.1136/annrheumdis-2017-211281
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