A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis
Autor: | Morton Scheinberg, Stanley Cohen, Tamas Shisha, Liyi Cen, Andra Balanescu, Josef S Smolen, Peijuan Zhu, Juan J. Gomez-Reino, Hans-Peter Tony, Alan Kivitz |
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Rok vydání: | 2017 |
Předmět: |
Male
DMARDs (biologic) Gastroenterology Arthritis Rheumatoid 0302 clinical medicine Clinical endpoint Immunology and Allergy Medicine Immunogenicity Middle Aged Treatment Outcome Antirheumatic Agents Area Under Curve 030220 oncology & carcinogenesis Rheumatoid arthritis Vitamin B Complex Drug Therapy Combination Female Rituximab medicine.drug Adult medicine.medical_specialty Adolescent Immunology Bioequivalence General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences Folic Acid Double-Blind Method Rheumatology Pharmacokinetics Internal medicine Humans Biosimilar Pharmaceuticals Aged 030203 arthritis & rheumatology B cells business.industry Clinical and Epidemiological Research medicine.disease Surgery Methotrexate Therapeutic Equivalency Pharmacodynamics business |
Zdroj: | Annals of the Rheumatic Diseases |
ISSN: | 1468-2060 0003-4967 |
Popis: | ObjectivesThe 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.MethodsIn 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 (AUC0-inf). Additional PK and PD parameters, along with efficacy, immunogenicity and safety outcomes were also assessed up to week 24.ResultsThe 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.ConclusionsThree-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 numberNCT01274182; Results. |
Databáze: | OpenAIRE |
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