Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study

Objectives To complete reporting of outcomes after total withdrawal of all rheumatoid arthritis (RA) therapy and re-treatment after flare in Assessing Very Early Rheumatoid arthritis Treatment study (NCT01142726).Methods Patients with early RA were initially randomised to double-blind, weekly subcu...

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Main Authors: Daniel E Furst, Paul Emery, Gerd R Burmester, Vivian P Bykerk, Bernard G Combe, Michael A Maldonado, Tom WJ Huizinga
Format: Article
Language:English
Published: BMJ Publishing Group 2019-06-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/5/1/e000840.full
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author Daniel E Furst
Paul Emery
Gerd R Burmester
Vivian P Bykerk
Bernard G Combe
Michael A Maldonado
Tom WJ Huizinga
author_facet Daniel E Furst
Paul Emery
Gerd R Burmester
Vivian P Bykerk
Bernard G Combe
Michael A Maldonado
Tom WJ Huizinga
author_sort Daniel E Furst
collection DOAJ
description Objectives To complete reporting of outcomes after total withdrawal of all rheumatoid arthritis (RA) therapy and re-treatment after flare in Assessing Very Early Rheumatoid arthritis Treatment study (NCT01142726).Methods Patients with early RA were initially randomised to double-blind, weekly subcutaneous abatacept plus methotrexate, or abatacept or methotrexate monotherapy. At month 12, patients with Disease Activity Score (DAS)28 C reactive protein (CRP) <3.2 had all RA treatments rapidly withdrawn and were observed for ≤12 months or until flare. After ≥3 months’ withdrawal, patients with protocol-defined RA flare received open-label abatacept plus methotrexate for 6 months (re-treatment).Results  Proportion of patients in DAS28-CRP–defined remission remained numerically higher in original abatacept plus methotrexate and abatacept arms versus methotrexate arm up to day 253 of withdrawal. At the end of the withdrawal period, few patients remained in remission across all arms: 9/73 (12.3%), 7/50 (14.0%) and 6/53 (11.3%), respectively. For patients entering re-treatment, after 6 months’ re-treatment, 95/124 (76.6%) and 78/124 (62.9%) patients achieved DAS28-CRP <3.2 and <2.6, respectively; mean changes in DAS28-CRP and Health Assessment Questionnaire–Disability Index scores from re-treatment baseline were –2.87 and 0.76, respectively. Re-treatment was well tolerated; exposure-adjusted infection rates per 100 patient-years were lower with abatacept plus methotrexate during withdrawal (7.2) and re-treatment (17.2) versus initial treatment periods of months 0–6 (116.6) and 6–12 (64.6).Conclusions Most patients flared within 6 months of therapy withdrawal and few sustained major responses for 1 year. Re-treatment with abatacept plus methotrexate was effective and well tolerated in this controlled setting.
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spelling doaj-art-d9a1e3f6b94940438fe3ab81ec51b2bb2025-08-20T03:25:27ZengBMJ Publishing GroupRMD Open2056-59332019-06-015110.1136/rmdopen-2018-000840Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT studyDaniel E Furst0Paul Emery1Gerd R Burmester2Vivian P Bykerk3Bernard G Combe4Michael A Maldonado5Tom WJ Huizinga66 Division of Rheumatology, University of California Los Angeles, Los Angeles, California, USADepartment of Rheumatology, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Biomedical Research Centre, Leeds, UKDepartment of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany4 Division of Rheumatology, Hospital for Special Surgery, New York, New York, USA5 Department of Rheumatology, CHU Montpellier, Montpellier University, Montpellier, France7 Immunoscience, Bristol-Myers Squibb, Princeton, New Jersey, USA8 Department of Rheumatology, Leiden University Medical Center, Leiden, NetherlandsObjectives To complete reporting of outcomes after total withdrawal of all rheumatoid arthritis (RA) therapy and re-treatment after flare in Assessing Very Early Rheumatoid arthritis Treatment study (NCT01142726).Methods Patients with early RA were initially randomised to double-blind, weekly subcutaneous abatacept plus methotrexate, or abatacept or methotrexate monotherapy. At month 12, patients with Disease Activity Score (DAS)28 C reactive protein (CRP) <3.2 had all RA treatments rapidly withdrawn and were observed for ≤12 months or until flare. After ≥3 months’ withdrawal, patients with protocol-defined RA flare received open-label abatacept plus methotrexate for 6 months (re-treatment).Results  Proportion of patients in DAS28-CRP–defined remission remained numerically higher in original abatacept plus methotrexate and abatacept arms versus methotrexate arm up to day 253 of withdrawal. At the end of the withdrawal period, few patients remained in remission across all arms: 9/73 (12.3%), 7/50 (14.0%) and 6/53 (11.3%), respectively. For patients entering re-treatment, after 6 months’ re-treatment, 95/124 (76.6%) and 78/124 (62.9%) patients achieved DAS28-CRP <3.2 and <2.6, respectively; mean changes in DAS28-CRP and Health Assessment Questionnaire–Disability Index scores from re-treatment baseline were –2.87 and 0.76, respectively. Re-treatment was well tolerated; exposure-adjusted infection rates per 100 patient-years were lower with abatacept plus methotrexate during withdrawal (7.2) and re-treatment (17.2) versus initial treatment periods of months 0–6 (116.6) and 6–12 (64.6).Conclusions Most patients flared within 6 months of therapy withdrawal and few sustained major responses for 1 year. Re-treatment with abatacept plus methotrexate was effective and well tolerated in this controlled setting.https://rmdopen.bmj.com/content/5/1/e000840.full
spellingShingle Daniel E Furst
Paul Emery
Gerd R Burmester
Vivian P Bykerk
Bernard G Combe
Michael A Maldonado
Tom WJ Huizinga
Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study
RMD Open
title Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study
title_full Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study
title_fullStr Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study
title_full_unstemmed Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study
title_short Re-treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis: 2-year results from the AVERT study
title_sort re treatment with abatacept plus methotrexate for disease flare after complete treatment withdrawal in patients with early rheumatoid arthritis 2 year results from the avert study
url https://rmdopen.bmj.com/content/5/1/e000840.full
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