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Efficacy of initial methotrexate monotherapy versus combination therapy with a biological agent in early rheumatoid arthritis: a meta-analysis of clinical and radiographic remission
  1. B Kuriya1,2,
  2. E V Arkema1,
  3. V P Bykerk2,
  4. E C Keystone2
  1. 1Harvard School of Public Health, Boston, Massachusetts, USA
  2. 2Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, University of Toronto, Toronto, Canada
  1. Correspondence to Dr B Kuriya., Rebecca MacDonald Centre for Arthritis and Autoimmune Diseases, Mount Sinai Hospital, Joseph and Wolf Lebovic Building, Toronto, Ontario M5T 3L9, Canada; bindee.kuriya{at}


Objective The target outcome in early rheumatoid arthritis (ERA) is now remission. This meta-analysis compared the efficacy of initial methotrexate monotherapy versus combination therapy (methotrexate plus biological agent) for clinical remission and radiographic non-progression among ERA patients with minimal or no previous methotrexate exposure.

Methods A systematic search was performed for randomised controlled trials of ERA using predefined criteria. A random effects model was used to pool the risk ratio (RR) for clinical and radiographic remission at 52–56 weeks of follow-up.

Results Seven trials of combination therapy with infliximab, adalimumab, etanercept or abatacept were included. The majority of studies defined clinical remission as a 28-joint disease activity score (DAS28) of 2.6 or less. Radiographic non-progression was primarily defined as a modified total Sharp score change of less than 0.5 units. All trials demonstrated risk estimates in favour of combination therapy: the pooled RR for achieving clinical remission was 1.74 (95% CI 1.54 to 1.98) and for radiographic non-progression was 1.30 (95% CI 1.01 to 1.68). Significant heterogeneity among studies for the latter outcome was detected (p<0.001).

Conclusions The efficacy of combination therapy with a biological agent is superior to methotrexate monotherapy for remission. Combination therapy has a greater initial effect on clinical remission than radiographic non-progression. Uniform definitions of remission are needed and the proportion of subjects who achieve the combined endpoint of clinical and radiographic remission should be considered as a meaningful outcome in future studies of ERA.

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  • Competing interests ECK has in the past received funding for research from Abbott, Amgen, Schering Plough and UCB, all companies that market anti-TNF therapies. VPB has received research funding from Amgen/Wyeth.

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