Background/Purpose: The goal of rheumatoid arthritis (RA) treatment is remission or, when not achievable, low-disease-activity (LDA). Initial combined therapy with MTX + anti-TNF achieves these goals more often but at a high cost. Some trials have therefore used the combined treatment for a limited time only (“induction-maintenance”). However, 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+Adalimumab 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 12-52 weeks of follow-up comparing patients who started with MTX+ADA to those who started with MTX alone. A random effects model was used to pool the risk ratio (RR) for clinical remission and LDA.

Results: The literature search identified 2810 studies that matched the predefined search terms. We identified four published randomized trials (Table 1), where MTX+ADA was given as initial therapy and where ADA was withdrawn in a subset of patients after LDA/remission had been achieved.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. As expected, the RR of achieving clinical remission or LDA with combination therapy was significantly greater than with MTX monotherapy; 1.76 (95%CI 1.51-2.06) and 1.45 (95%CI 1.03-2.08), respectively. Most importantly, the pooled RRs for achieving clinical remission and LDA at follow-up after discontinuation of ADA were 1.30 (95%CI 0.90-1.87) and 1.22 (95%CI 0.95-1.58), respectively, with significant heterogeneity between trials. Opera featured consistent use of intra-articular glucocorticoid-injections as a treat-to target strategy and therefore a sensitivity analysis excluding Opera was performed where the pooled RR for achieving clinical remission and LDA, at follow-up after discontinuation of ADA, were 1.56 (95%CI 1.21-2.00) and 1.37 (95%CI 1.09-1.72), respectively, without significant heterogeneity (Figure 1).

Conclusion: This meta-analysis supports the hypothesis that in early RA, initial therapy with MTX+ADA is associated with a higher chance of retaining LDA and/or remission even after discontinuation of ADA.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/induction-maintenance-in-early-ra-a-meta-analysis-of-trials-using-mtx-plus-adalimumab-as-induction-therapy/