Background 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”).
Objectives 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.
Methods 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<3.2) and/or remission (DAS28<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.
Results 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identified six published randomized trials, four of them where MTX+ADA was given as initial therapy and where ADA was withdrawn in a subset of patients after LDA/remission had been achieved.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).
Conclusions 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.
Acknowledgement Dr. Marc Quinn at York Teaching Hospital.
Disclosure of Interest 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