Article Text

Download PDFPDF

Original article
Induction maintenance with tumour necrosis factor-inhibitor combination therapy with discontinuation versus methotrexate monotherapy in early rheumatoid arthritis: a systematic review and meta-analysis of efficacy in randomised controlled trials
  1. Sharzad Emamikia1,
  2. Elizabeth V Arkema2,
  3. Noémi Györi1,
  4. Jacqueline Detert3,
  5. Katerina Chatzidionysiou1,
  6. Maxime Dougados4,
  7. Gerd Rüdiger Burmester3 and
  8. Ronald van Vollenhoven1,5
  1. 1Department of Medicine, ClinTRID, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
  2. 2Clinical Epidemiology Unit, Karolinska Institute, Stockholm, Sweden
  3. 3Charité—Universitätsmedizin, Berlin, Institute of Clinical Immunology and Rheumatology, Berlin, Germany
  4. 4Department of Rheumatology, Paris Descartes University, Hôpital Cochin. Assistance Publique—Hôpitaux de Paris INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France
  5. 5Department of Clinical Immunology & Rheumatology, Academic Medical Center, Amsterdam, The Netherlands
  1. Correspondence to Sharzad Emamikia; sharzad.emamikia{at}ki.se

Abstract

Objective To determine whether an induction-maintenance strategy of combined therapy (methotrexate (MTX)+tumour necrosis factor (TNF) inhibitor (TNFi)) followed by withdrawal of TNFi could yield better long-term results than a strategy with MTX monotherapy, since it is unclear if the benefits from an induction phase with combined therapy are sustained if TNFi is withdrawn.

Methods We performed a meta-analysis of trials using the initial combination of MTX+TNFi in conventional synthetic disease-modifying antirheumatic drug-naïve patients with early rheumatoid arthritis (RA). A systematic literature search was performed for induction-maintenance randomised controlled trials (RCTs) where initial combination therapy was compared with MTX monotherapy in patients with clinically active early RA. Our primary outcome was the proportion of patients who achieved low disease activity (LDA; Disease Activity Score (DAS)28<3.2) and/or remission (DAS28<2.6) at 12–76 weeks of follow-up. A random-effects model was used to pool the risk ratio (RR) for LDA and remission and heterogeneity was explored by subgroup analyses.

Results We identified 6 published RCTs, 4 of them where MTX+adalimumab was given as initial therapy and where adalimumab was withdrawn in a subset of patients after LDA/remission had been achieved. 2 additional trials used MTX+infliximab as combination therapy. The pooled RRs for achieving LDA and clinical remission at follow-up after withdrawal of TNFi were 1.41 (95% CI 1.05 to 1.89) and 1.34 (95% CI 0.95 to 1.89), respectively. There was significant heterogeneity between trials due to different treatment strategies, which was a limitation to this study.

Conclusions Initial therapy with MTX+TNFi is associated with a higher chance of retaining LDA and/or remission even after discontinuation of TNFi.

  • Early Rheumatoid Arthritis
  • Anti-TNF
  • Treatment
  • Methotrexate
  • Disease Activity

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 and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.