FRI0190 Induction-Maintenance in Early RA: A Meta-Analysis of Trials Using MTX plus TNF-Inhibitor as Induction Therapy
Authors: S. Emamikia, E.V. Arkema, J. Detert, K. Chatzidionysiou, M. Dougados, G.R. Burmester, R.F. van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The goal of rheumatoid arthritis (RA) treatment is remission or, when not achievable, low-disease-activity (LDA). Initial combined therapy with MTX + TNF-inhibitor (TNFi) achieves these goals more often than MTX alone, but at a high cost. Some trials have therefore used the combined treatment for a limited time only ("induction-maintenance"). <h3>Objectives</h3> It has remained unclear if the benefits from the induction phase are sustained during maintenance, and individual trials may not have been sufficiently powered to resolve this issue. Therefore, we performed a meta-analysis of trials using the initial combination of MTX+ TNFi in DMARD-naïve early RA-patients. <h3>Methods</h3> A systematic literature search was performed for induction-maintenance randomized controlled trials 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 LDA (DAS28&lt;3.2) and/or remission (DAS28&lt;2.6), at 12–76 weeks of follow-up comparing patients who started with MTX+TNFi to those who started with MTX alone. A random effects model was used to pool the risk ratio (RR) for LDA and clinical remission. <h3>Results</h3> The literature search identified 1269 studies that matched the predefined search terms. We identified six published randomized trials, four of them where MTX+ADA was given as initial therapy and where ADA was withdrawn in a subset of patients after LDA/remission had been achieved. For two of these trials (Guépard and Hit-Hard) original data were re-examined, for the other two (Optima and Opera) only published data were available. Two of the additional identified trials (T20 and BeST) used MTX+Infliximab as initial combination- therapy. For BeST, only LDA could be assessed. As expected, the RR of achieving LDA or clinical remission with combination therapy was significantly greater than with MTX monotherapy; 1.70 (95%CI 1.21–2.38) and 1.67 (95%CI 1.42–1.95), respectively. The pooled RRs for achieving LDA and clinical remission at follow-up after discontinuation of TNFi were 1.41 (95%CI 1.05–1.89) and 1.34 (95%CI 0.95–1.89), respectively, with significant heterogeneity between trials (Figure 1). <h3>Conclusions</h3> This meta-analysis supports the hypothesis that in early RA, initial therapy with MTX+TNFi is associated with a higher chance of retaining LDA and/or remission even after discontinuation of TNFi. <h3>Acknowledgement</h3> Dr. Marc Quinn at York Teaching Hospital. <h3>Disclosure of Interest</h3> S. Emamikia: None declared, E. Arkema: None declared, J. Detert: None declared, K. Chatzidionysiou: None declared, M. Dougados Consultant for: Maxime Dougados has participated at symposia and advisory boards organized by ABBVIE, PFIZER, UCB, MERCK, SANOFI, NOVARTIS, ROCHE, BMS, G. Burmester Grant/research support from: Abbott, R. van Vollenhoven Grant/research support from: AbbVie, Amgen, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, Crescendo, GSK, Janssen, Lilly, Merck, Pfizer, Roche, UCB, Vertex