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Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial

OBJECTIVE: To evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexate (MTX). METHODS: This 52-week, multicentre,...

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Autores principales: Combe, Bernard, Kivitz, Alan, Tanaka, Yoshiya, van der Heijde, Désirée, Simon, J Abraham, Baraf, Herbert S B, Kumar, Uma, Matzkies, Franziska, Bartok, Beatrix, Ye, Lei, Guo, Ying, Tasset, Chantal, Sundy, John S, Jahreis, Angelika, Genovese, Mark C, Mozaffarian, Neelufar, Landewé, Robert B M, Bae, Sang-Cheol, Keystone, Edward C, Nash, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237199/
https://www.ncbi.nlm.nih.gov/pubmed/33504485
http://dx.doi.org/10.1136/annrheumdis-2020-219214
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author Combe, Bernard
Kivitz, Alan
Tanaka, Yoshiya
van der Heijde, Désirée
Simon, J Abraham
Baraf, Herbert S B
Kumar, Uma
Matzkies, Franziska
Bartok, Beatrix
Ye, Lei
Guo, Ying
Tasset, Chantal
Sundy, John S
Jahreis, Angelika
Genovese, Mark C
Mozaffarian, Neelufar
Landewé, Robert B M
Bae, Sang-Cheol
Keystone, Edward C
Nash, Peter
author_facet Combe, Bernard
Kivitz, Alan
Tanaka, Yoshiya
van der Heijde, Désirée
Simon, J Abraham
Baraf, Herbert S B
Kumar, Uma
Matzkies, Franziska
Bartok, Beatrix
Ye, Lei
Guo, Ying
Tasset, Chantal
Sundy, John S
Jahreis, Angelika
Genovese, Mark C
Mozaffarian, Neelufar
Landewé, Robert B M
Bae, Sang-Cheol
Keystone, Edward C
Nash, Peter
author_sort Combe, Bernard
collection PubMed
description OBJECTIVE: To evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexate (MTX). METHODS: This 52-week, multicentre, double-blind, placebo-controlled and active-controlled phase III trial evaluated once-daily oral filgotinib in patients with RA randomised 3:3:2:3 to filgotinib 200 mg (FIL200) or filgotinib 100 mg (FIL100), subcutaneous adalimumab 40 mg biweekly, or placebo (through week 24), all with stable weekly background MTX. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Additional efficacy outcomes were assessed sequentially. Safety was assessed from adverse events and laboratory abnormalities. RESULTS: The proportion of patients (n=1755 randomised and treated) achieving ACR20 at week 12 was significantly higher for FIL200 (76.6%) and FIL100 (69.8%) versus placebo (49.9%; treatment difference (95% CI), 26.7% (20.6% to 32.8%) and 19.9% (13.6% to 26.2%), respectively; both p<0.001). Filgotinib was superior to placebo in key secondary endpoints assessing RA signs and symptoms, physical function and structural damage. FIL200 was non-inferior to adalimumab in terms of Disease Activity Score in 28 joints with C reactive protein ≤3.2 at week 12 (p<0.001); FIL100 did not achieve non-inferiority. Adverse events and laboratory abnormalities were comparable among active treatment arms. CONCLUSIONS: Filgotinib improved RA signs and symptoms, improved physical function, inhibited radiographic progression and was well tolerated in patients with RA with inadequate response to MTX. FIL200 was non-inferior to adalimumab. TRIAL REGISTRATION NUMBER: NCT02889796.
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spelling pubmed-82371992021-07-09 Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial Combe, Bernard Kivitz, Alan Tanaka, Yoshiya van der Heijde, Désirée Simon, J Abraham Baraf, Herbert S B Kumar, Uma Matzkies, Franziska Bartok, Beatrix Ye, Lei Guo, Ying Tasset, Chantal Sundy, John S Jahreis, Angelika Genovese, Mark C Mozaffarian, Neelufar Landewé, Robert B M Bae, Sang-Cheol Keystone, Edward C Nash, Peter Ann Rheum Dis Rheumatoid Arthritis OBJECTIVE: To evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexate (MTX). METHODS: This 52-week, multicentre, double-blind, placebo-controlled and active-controlled phase III trial evaluated once-daily oral filgotinib in patients with RA randomised 3:3:2:3 to filgotinib 200 mg (FIL200) or filgotinib 100 mg (FIL100), subcutaneous adalimumab 40 mg biweekly, or placebo (through week 24), all with stable weekly background MTX. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Additional efficacy outcomes were assessed sequentially. Safety was assessed from adverse events and laboratory abnormalities. RESULTS: The proportion of patients (n=1755 randomised and treated) achieving ACR20 at week 12 was significantly higher for FIL200 (76.6%) and FIL100 (69.8%) versus placebo (49.9%; treatment difference (95% CI), 26.7% (20.6% to 32.8%) and 19.9% (13.6% to 26.2%), respectively; both p<0.001). Filgotinib was superior to placebo in key secondary endpoints assessing RA signs and symptoms, physical function and structural damage. FIL200 was non-inferior to adalimumab in terms of Disease Activity Score in 28 joints with C reactive protein ≤3.2 at week 12 (p<0.001); FIL100 did not achieve non-inferiority. Adverse events and laboratory abnormalities were comparable among active treatment arms. CONCLUSIONS: Filgotinib improved RA signs and symptoms, improved physical function, inhibited radiographic progression and was well tolerated in patients with RA with inadequate response to MTX. FIL200 was non-inferior to adalimumab. TRIAL REGISTRATION NUMBER: NCT02889796. BMJ Publishing Group 2021-07 2021-01-27 /pmc/articles/PMC8237199/ /pubmed/33504485 http://dx.doi.org/10.1136/annrheumdis-2020-219214 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/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, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Rheumatoid Arthritis
Combe, Bernard
Kivitz, Alan
Tanaka, Yoshiya
van der Heijde, Désirée
Simon, J Abraham
Baraf, Herbert S B
Kumar, Uma
Matzkies, Franziska
Bartok, Beatrix
Ye, Lei
Guo, Ying
Tasset, Chantal
Sundy, John S
Jahreis, Angelika
Genovese, Mark C
Mozaffarian, Neelufar
Landewé, Robert B M
Bae, Sang-Cheol
Keystone, Edward C
Nash, Peter
Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial
title Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial
title_full Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial
title_fullStr Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial
title_full_unstemmed Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial
title_short Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial
title_sort filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase iii randomised clinical trial
topic Rheumatoid Arthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237199/
https://www.ncbi.nlm.nih.gov/pubmed/33504485
http://dx.doi.org/10.1136/annrheumdis-2020-219214
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