Study: Methotrexate Combination Offers Rheumatoid Arthritis Benefit

New research finds a connection between initiating treatment for early rheumatoid arthritis (RA) with methotrexate plus a tumor necrosis factor inhibitor (TNFi) and a greater chance of retaining low disease activity and/or remission compared with using methotrexate alone.

The authors undertook the study to determine whether an induction-maintenance strategy of combined therapy followed by withdrawal of TNFi could yield better long-term results than a strategy with methotrexate monotherapy, since it is unclear if the benefits from an induction phase with combined therapy are sustained if TNFi is withdrawn.
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The investigators performed a meta-analysis of trials using the initial combination of methotrexate and TNFi in conventional synthetic disease-modifying antirheumatic drug-naïve patients with early RA. The authors performed a systematic literature search for induction-maintenance randomized controlled trials in which initial combination therapy was compared with methotrexate monotherapy in patients with clinically active early RA. The primary outcome was the proportion of patients who achieved low disease activity and/or remission at 12 to 76 weeks of follow-up. The team used a random-effects model to pool the risk ratio for low disease activity and remission and heterogeneity was explored by subgroup analyses.

Ultimately, 6 published randomized controlled trials were identified. Among these trials, the researchers identified 4 in which methotrexate and adalimumab were administered as initial therapy and where adalimumab was withdrawn in a subset of patients after low disease activity or remission had been achieved, with 2 additional trials using methotrexate plus infliximab as combination therapy. Significant heterogeneity between trials existed due to different treatment strategies, which was a limitation to this study, according to the authors, who conclude that initial therapy with methotrexate and tumor necrosis factor inhibitor was associated with an increased likelihood of retaining low disease activity and/or remission, even after discontinuation of TNFi.

"Rheumatoid arthritis, a potentially serious disease, can be treated effectively with a number of different medications, and choosing the right medication or combination of medications from the beginning has become more important than ever," said Ronald van Vollenhoven, MD, PhD, professor of rheumatology and director at the Amsterdam Rheumatology and Immunology Center ARC, and study co-author.

"That is why I would say that the best thing a primary care physician can do for their patient who may have developed RA," he said, "is to refer them to a rheumatology specialist as quickly as possible."

—Mark McGraw

Reference:

Emamikia S, Arkema EV, Györi N, et al. 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 randomized controlled trials [published online September 6, 2016]. RMD Open. doi:10.1136/rmdopen-2016-000323.