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Risk of losing remission, low disease activity or radiographic progression in case of bDMARD discontinuation or tapering in rheumatoid arthritis: systematic analysis of the literature and meta-analysis
  1. Sophie Henaux1,2,
  2. Adeline Ruyssen-Witrand1,2,3,
  3. Alain Cantagrel1,2,4,
  4. Thomas Barnetche5,
  5. Bruno Fautrel6,
  6. Nathalie Filippi7,
  7. Cédric Lukas7,
  8. Bernd Raffeiner8,
  9. Maurizio Rossini9,
  10. Yannick Degboé1,2,4,
  11. Arnaud Constantin1,2,4
  1. 1Centre de Rhumatologie, Hôpital Purpan, Toulouse, France
  2. 2Faculté de Médecine, Université Toulouse III, Paul Sabatier University, Toulouse, France
  3. 3Faculté de Médecine, UMR1027, Toulouse, France
  4. 4INSERM UMR 1043, CHU Purpan, Toulouse, France
  5. 5Service de Rhumatologie, Groupe Hospitalier Pellegrin, Bordeaux, France
  6. 6Service de Rhumatologie, Hôpital Universitaire Pitié-Salpêtrière, Paris, France
  7. 7Département de Rhumatologie, Centre Hospitalier Universitaire, Montpellier, France
  8. 8Rheumatology Unit, Department of Medicine – DIMED, University of Padova, Padova, Italy
  9. 9Rheumatology Unit, University of Verona, Verona, Italy
  1. Correspondence to Dr Adeline Ruyssen-Witrand, Centre de Rhumatologie, Hôpital Purpan, CHU Toulouse, Toulouse 31059, France; ruyssen-witrand.a{at}chu-toulouse.fr

Abstract

Objectives To assess the risk of losing remission, low disease activity (LDA) or radiographic progression in the case of (1) discontinuing or (2) tapering doses of biological disease-modifying antirheumatic drugs (bDMARDs) compared with continuation of the initial treatment regimen in rheumatoid arthritis (RA) patients with remission or LDA.

Materials and methods A systematic literature analysis was carried out through May 2017 on the PubMed, Embase, Cochrane and international congress databases, selecting controlled trials comparing bDMARDs discontinuation/tapering versus continuation in RA patients with remission or LDA. The meta-analysis assessed the risk ratio (RR) and 95% CI of losing remission or LDA and the risk of radiographic progression after (1) discontinuing and (2) tapering doses of bDMARDs versus continuing the initial treatment.

Results The meta-analysis comparing bDMARDs discontinuation versus continuation performed on nine trials showed an increased risk of losing remission (RR (95% CI)=1.97(1.43 to 2.73), P<0.0001) or LDA (RR (95% CI)=2.24(1.52 to 3.30), P<0.0001) and an increased risk of radiographic progression (RR (95% CI)=1.09(1.02 to 1.17), P=0.01) in case of bDMARD discontinuation. The meta-analysis comparing bDMARDs tapering versus continuation performed on 11 trials showed an increased risk of losing remission (RR (95% CI)=1.23(1.06 to 1.42), P=0.006) but no increased risk of losing LDA (RR (95% CI)=1.02 (0.85 to 1.23), P=0.81) nor any increased risk of radiographic progression (RR (95% CI)=1.09(0.94 to 1.26), P=0.26) in case of bDMARD tapering.

Conclusion Discontinuation of bDMARDs leads to an increased risk of losing remission or LDA and radiographic progression, while tapering doses of bDMARDs does not increase the risk of relapse (LDA) or radiographic progression, even though there is an increased risk of losing remission.

  • rheumatoid arthritis
  • das28
  • dmards (biologic)
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Footnotes

  • SH and AR-W contributed equally.

  • Handling editor Josef S Smolen

  • Contributors SH and ARW equally contributed to the conception of the study, the article selection process, the data collection, the data analysis, the results interpretation and the manuscript writing and approval. CL and NF contributed to the conception of the study, the article selection process and data collection. TB was in charge of the statistical analyses. BF, BR and MR sent additional data from their trials that permitted to improve the data pooling. YD, AC and ARC contributed to the conception of the study, results interpretation and manuscript approval. All authors take responsibility for the integrity of the work as a whole, from inception to published article, and they should indicate that they had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. They give permission to reproduce published material, report sensitive personal information, to use illustrations of identifiable persons, or to name persons for their contributions.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The Ethics Committee approvals of each trial was obtained for all the studies selected in this meta-analysis.

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

  • Data sharing statement This study involved only published reports and none unpublished information. No database was used for this study.

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