Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54

Objective To investigate the efficacy, safety and immunogenicity of PF-06438179/GP1111 (PF-SZ-IFX) compared with European reference infliximab (Remicade®; ref-IFX) in patients with moderate-to-severe, active rheumatoid arthritis after continued long-term use of PF-SZ-IFX, and in patients who were sw...

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Main Authors: Goran Babic, Hideto Kameda, Rieke Alten, Bogdan Batko, Tomas Hala, Sebastiao C Radominski, Vira Tseluyko, Carol Cronenberger, Sarah Hackley, Muhammad Rehman, Oliver von Richter, Min Zhang, Stanley Cohen
Format: Article
Language:English
Published: BMJ Publishing Group 2019-05-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/5/1/e000876.full
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author Goran Babic
Hideto Kameda
Rieke Alten
Bogdan Batko
Tomas Hala
Sebastiao C Radominski
Vira Tseluyko
Carol Cronenberger
Sarah Hackley
Muhammad Rehman
Oliver von Richter
Min Zhang
Stanley Cohen
author_facet Goran Babic
Hideto Kameda
Rieke Alten
Bogdan Batko
Tomas Hala
Sebastiao C Radominski
Vira Tseluyko
Carol Cronenberger
Sarah Hackley
Muhammad Rehman
Oliver von Richter
Min Zhang
Stanley Cohen
author_sort Goran Babic
collection DOAJ
description Objective To investigate the efficacy, safety and immunogenicity of PF-06438179/GP1111 (PF-SZ-IFX) compared with European reference infliximab (Remicade®; ref-IFX) in patients with moderate-to-severe, active rheumatoid arthritis after continued long-term use of PF-SZ-IFX, and in patients who were switched from ref-IFX to PF-SZ-IFX.Methods REFLECTIONS B537-02 was a double-blind, active-controlled, multinational study in which patients (N=650) were initially randomised to PF-SZ-IFX or ref-IFX for 30 weeks (treatment period [TP] 1). During weeks 30–54 (TP2), the PF-SZ-IFX group (n=280) continued treatment with PF-SZ-IFX (PF-SZ-IFX/PF-SZ-IFX) and patients in the ref-IFX group (n=286) were rerandomised (1:1) to continue ref-IFX (ref-IFX/ref-IFX) (n=143) or switch to PF-SZ-IFX (ref-IFX/PF-SZ-IFX) (n=143) for a further 24 weeks. Efficacy, safety, immunogenicity and pharmacokinetics were evaluated.Results During TP2, patients in all three treatment groups continued to maintain comparable treatment response. At week 54, the American College of Rheumatology (ACR20) response rates were 71.1% (PF-SZ-IFX/PF-SZ-IFX), 64.3% (ref-IFX/ref-IFX) and 70.6% (ref-IFX/PF-SZ-IFX). Observations for other endpoints, including ACR50/70, Disease Activity Score in 28 Joints Based on High-Sensitivity C Reactive Protein(DAS28-CRP) remission, and mean change in DAS28-CRP and Health Assessment Questionnaire-Disability Index, were also comparable. Treatment-emergent adverse events were reported in 36.8% (PF-SZ-IFX/PF-SZ-IFX), 33.6% (ref-IFX/ref-IFX) and 37.8% (ref-IFX/PF-SZ-IFX) of patients; there were no clinically meaningful differences in the safety profiles between groups. The percentage of patients who were antidrug antibody-positive was generally stable through the treatment period and comparable overall between the PF-SZ-IFX/PF-SZ-IFX (52.1%; neutralising: 80.8%), ref-IFX/ref-IFX (60.1%; neutralising: 84.9%) and ref-IFX/PF-SZ-IFX (58.0%; neutralising 78.3%) groups.Conclusions The similar efficacy, safety and immunogenicity of PF-SZ-IFX compared with ref-IFX were maintained for up to 54 weeks and were not affected by blinded treatment switch from ref-IFX to PF-SZ-IFX at week 30.Trial registration number NCT02222493.
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spelling doaj-art-e37b8a4fa15d474a93a3b6cb879bb5f52025-08-20T03:25:25ZengBMJ Publishing GroupRMD Open2056-59332019-05-015110.1136/rmdopen-2018-000876Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54Goran Babic0Hideto Kameda1Rieke Alten2Bogdan Batko3Tomas Hala4Sebastiao C Radominski5Vira Tseluyko6Carol Cronenberger7Sarah Hackley8Muhammad Rehman9Oliver von Richter10Min Zhang11Stanley Cohen12Sandoz Biopharmaceuticals, Hexal (a Sandoz company), Holzkirchen, GermanyToho University Ohashi Medical Center, Tokyo, JapanUniversity Medicine, Schlosspark Klinik, Berlin, GermanyJ Dietl Specialist Hospital, Krakow, PolandCenter for Clinical and Basic Research, Pardubice, Czech RepublicUniversidade Federal do Paraná, Curitiba, BrazilKharkiv Medical Academy of Postgraduate Education, Kharkiv, UkrainePfizer, Collegeville, Pennsylvania, USAPfizer, Sandwich, Kent, UKPfizer, Andover, Massachusetts, USASandoz Biopharmaceuticals, Hexal (a Sandoz company), Holzkirchen, GermanyDepartment of Endocrinology, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaMetroplex Clinical Research Center, Dallas, Texas, USAObjective To investigate the efficacy, safety and immunogenicity of PF-06438179/GP1111 (PF-SZ-IFX) compared with European reference infliximab (Remicade®; ref-IFX) in patients with moderate-to-severe, active rheumatoid arthritis after continued long-term use of PF-SZ-IFX, and in patients who were switched from ref-IFX to PF-SZ-IFX.Methods REFLECTIONS B537-02 was a double-blind, active-controlled, multinational study in which patients (N=650) were initially randomised to PF-SZ-IFX or ref-IFX for 30 weeks (treatment period [TP] 1). During weeks 30–54 (TP2), the PF-SZ-IFX group (n=280) continued treatment with PF-SZ-IFX (PF-SZ-IFX/PF-SZ-IFX) and patients in the ref-IFX group (n=286) were rerandomised (1:1) to continue ref-IFX (ref-IFX/ref-IFX) (n=143) or switch to PF-SZ-IFX (ref-IFX/PF-SZ-IFX) (n=143) for a further 24 weeks. Efficacy, safety, immunogenicity and pharmacokinetics were evaluated.Results During TP2, patients in all three treatment groups continued to maintain comparable treatment response. At week 54, the American College of Rheumatology (ACR20) response rates were 71.1% (PF-SZ-IFX/PF-SZ-IFX), 64.3% (ref-IFX/ref-IFX) and 70.6% (ref-IFX/PF-SZ-IFX). Observations for other endpoints, including ACR50/70, Disease Activity Score in 28 Joints Based on High-Sensitivity C Reactive Protein(DAS28-CRP) remission, and mean change in DAS28-CRP and Health Assessment Questionnaire-Disability Index, were also comparable. Treatment-emergent adverse events were reported in 36.8% (PF-SZ-IFX/PF-SZ-IFX), 33.6% (ref-IFX/ref-IFX) and 37.8% (ref-IFX/PF-SZ-IFX) of patients; there were no clinically meaningful differences in the safety profiles between groups. The percentage of patients who were antidrug antibody-positive was generally stable through the treatment period and comparable overall between the PF-SZ-IFX/PF-SZ-IFX (52.1%; neutralising: 80.8%), ref-IFX/ref-IFX (60.1%; neutralising: 84.9%) and ref-IFX/PF-SZ-IFX (58.0%; neutralising 78.3%) groups.Conclusions The similar efficacy, safety and immunogenicity of PF-SZ-IFX compared with ref-IFX were maintained for up to 54 weeks and were not affected by blinded treatment switch from ref-IFX to PF-SZ-IFX at week 30.Trial registration number NCT02222493.https://rmdopen.bmj.com/content/5/1/e000876.full
spellingShingle Goran Babic
Hideto Kameda
Rieke Alten
Bogdan Batko
Tomas Hala
Sebastiao C Radominski
Vira Tseluyko
Carol Cronenberger
Sarah Hackley
Muhammad Rehman
Oliver von Richter
Min Zhang
Stanley Cohen
Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54
RMD Open
title Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54
title_full Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54
title_fullStr Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54
title_full_unstemmed Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54
title_short Randomised, double-blind, phase III study comparing the infliximab biosimilar, PF-06438179/GP1111, with reference infliximab: efficacy, safety and immunogenicity from week 30 to week 54
title_sort randomised double blind phase iii study comparing the infliximab biosimilar pf 06438179 gp1111 with reference infliximab efficacy safety and immunogenicity from week 30 to week 54
url https://rmdopen.bmj.com/content/5/1/e000876.full
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