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  • 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

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Rheumatoid arthritis
Original article
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
  1. Paul Emery1,2,
  2. Gerd R Burmester3,
  3. Vivian P Bykerk4,
  4. Bernard G Combe5,
  5. Daniel E Furst6,
  6. Michael A Maldonado7 and
  7. Tom WJ Huizinga8
  1. 1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
  2. 2 NIHR Leeds Musculoskeletal Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  3. 3 Department of Rheumatology and Clinical Immunology, Charité – University Medicine Berlin, Berlin, Germany
  4. 4 Division of Rheumatology, Hospital for Special Surgery, New York, New York, USA
  5. 5 Department of Rheumatology, CHU Montpellier, Montpellier University, Montpellier, France
  6. 6 Division of Rheumatology, University of California Los Angeles, Los Angeles, California, USA
  7. 7 Immunoscience, Bristol-Myers Squibb, Princeton, New Jersey, USA
  8. 8 Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
  1. Correspondence to Dr Paul Emery; p.emery{at}leeds.ac.uk

Abstract

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3.2 had all RA treatments rapidly withdrawn and were observed for ≤12 months or until flare.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.

  • disease activity
  • DMARDs (biologic)
  • rheumatoid arthritis
  • methotrexate
  • remission

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://doi.org/10.1136/rmdopen-2018-000840

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    Footnotes

    • Contributors All authors were involved in the conception and design of the study, data acquisition and/or interpretation, drafting and critical revision of the manuscript, and final approval of the version to be published, and agree to be accountable for all aspects of the work.

    • Funding This study was funded by Bristol-Myers Squibb.

    • Competing interests PE: grant/research support: AbbVie, Merck, Pfizer, Roche; consultant: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, Lilly, Novartis, Samsung Bioepis. GRB: grant/research support: clinical trials for Bristol-Myers Squibb, AbbVie, Pfizer, Medimmune, Novartis, Roche, UCB, Lilly; consultant: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, MedImmune, Roche, UCB; speakers bureau: Bristol-Myers Squibb, AbbVie, Pfizer, MSD, Roche, UCB. VPB: grant/research support: Amgen, Pfizer, Bristol-Myers Squibb, Janssen, UCB, Sanofi, Roche/Genentech; consultant: Amgen, AbbVie, Pfizer, Bristol-Myers Squibb, UCB, Roche, Regeneron. BGC: grant/research support: Pfizer, Roche-Chugai, UCB; honoraria/speakers bureau: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche-Chugai, UCB, Janssen, Lilly, Novartis, Sanofi. DEF: grant/research support: Amgen, Bristol-Myers Squibb, Pfizer, Roche/Genentech; consultant: AbbVie, Amgen, Bristol-Myers Squibb, Corbus, Cytori, Novartis, Pfizer, Roche/Genentech; speakers bureau: AbbVie, Bristol-Myers Squibb. MAM: shareholder and employee: Bristol-Myers Squibb. TWJH: grant/research support: EU and Dutch Arthritis Foundation; consultant: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Crescendo Bioscience, Novartis, Pfizer, Roche, Sanofi, Schering-Plough, UCB, Eli Lilly; speakers bureau: Abbott Laboratories, Biotest AG, Bristol-Myers Squibb, Novartis, Pfizer, Roche, Sanofi, Schering-Plough.

    • Patient consent for publication All patients or their legally acceptable representatives gave written, informed consent prior to study entry.

    • Ethics approval The AVERT study protocol was approved by the Institutional Review Board or Independent Ethics Committee at each site.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement BMS policy on data sharing may be found online (https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html).