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Low rates of remission with methotrexate monotherapy in rheumatoid arthritis: review of randomised controlled trials could point towards a paradigm shift
  1. Katerina Chatzidionysiou and
  2. Petros P Sfikakis
  1. First Department of Propaedeutic and Internal Medicine and Joined Rheumatology Program, Medical School, National and Kapodistrian University of Athens, Laikon Hospital, Athens, Greece
  1. Correspondence to Dr Katerina Chatzidionysiou; aikaterini.chatzidionysiou{at}


Treatment of rheumatoid arthritis (RA) has improved substantially during the last decades, mainly due to the development and introduction in everyday practice of new, highly efficacious, disease-modifying antirheumatic drugs (DMARDs), more optimal usage of them, earlier diagnosis and tighter control of disease activity targeting at remission. Methotrexate is still today the anchor drug and the first-line treatment after diagnosis. However, numerous studies comparing methotrexate and biologic DMARDs, as well as new targeted synthetic DMARDs, both in early as in more established disease, have shown consistently better efficacy of the latter compared with methotrexate, with methotrexate yielding remission to maximum half of patients. This could suggest a new paradigm shift with earlier start of a biologic or a targeted synthetic DMARD, with the possibility of subsequent discontinuation in case of achievement of stable remission. Several strategy trials, however, have shown that there might be a clinical and structural benefit of initial, aggressive therapy, possibly even associated with higher chance of remaining in remission, after cessation of the biologic DMARD and continuing with methotrexate alone, but they have failed to show a clear advantage of such an aggressive treatment strategy. This might become a valuable option for the future treatment algorithm of RA, especially for a subgroup of patients with RA, but further confirmation from future research is needed. The crucial role of glucocorticoid use as part of the combination strategy should be acknowledged, and strategy trials should include this combination as an active comparator.

  • rheumatoid arthritis
  • dmards (biologic)
  • methotrexate

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  • Contributors Both authors contributed to conception, collection of data, analysis and critical interpretation of data, and preparation of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests KC has received consultant fees from AbbVie, Pfizer and Lilly. PPS has received consultant fees and research grants from AbbVie, Pfizer, MSD, Roche, UCB, GSK and Novartis.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No additional data are available.

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