title: 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.
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monotherapy, since it is unclear if the benefits from an induction phase with combined therapy are sustained if TNFi is withdrawn.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  We identified 6 published RCTs, 4 of them where MTX+adalimumab was given as initial therapy and where adalimumab was withdrawn in a subset of patients after LDA/remission had been achieved. 2 additional trials used MTX+infliximab as combination therapy.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.
authors.affiliation: Department of Medicine , ClinTRID, Solna, Karolinska Institutet, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Sharzad
authors.initials: S
authors.lastname: Emamikia
authors.affiliation: Clinical Epidemiology Unit , Karolinska Institute , Stockholm , Sweden.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Arkema
authors.affiliation: Department of Medicine , ClinTRID, Solna, Karolinska Institutet, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Noémi
authors.initials: N
authors.lastname: Györi
authors.affiliation: Charité-Universitätsmedizin, Berlin, Institute of Clinical Immunology and Rheumatology , Berlin , Germany.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Detert
authors.affiliation: Department of Medicine , ClinTRID, Solna, Karolinska Institutet, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Katerina
authors.initials: K
authors.lastname: Chatzidionysiou
authors.affiliation: Department of Rheumatology , Paris Descartes University, Hôpital Cochin. Assistance Publique-Hôpitaux de Paris INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité , Paris , France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.affiliation: Charité-Universitätsmedizin, Berlin, Institute of Clinical Immunology and Rheumatology , Berlin , Germany.
authors.forename: Gerd Rüdiger
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Department of Medicine, ClinTRID, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Clinical Immunology & Rheumatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Vollenhoven
keywords: Anti-TNF; Disease Activity; Early Rheumatoid Arthritis; Methotrexate; Treatment