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Extended report
Optimal methotrexate dose is associated with better clinical outcomes than non-optimal dose in daily practice: results from the ESPOIR early arthritis cohort
  1. Cécile Gaujoux-Viala1,2,
  2. Nathalie Rincheval2,
  3. Maxime Dougados3,
  4. Bernard Combe4,
  5. Bruno Fautrel5,6
  1. 1Department of Rheumatology, Nîmes University Hospital, Nîmes, France
  2. 2EA2415, Montpellier University, Montpellier, France
  3. 3Department of Rheumatology, Cochin Hospital, AP-HP, INSERM (U1153), PRES Sorbonne Paris-Cité, Paris Descartes University, Paris, France
  4. 4Department of Rheumatology, Lapeyronie Hospital, Montpellier University, Montpellier, France
  5. 5GRC-UPMC 08, Institut Pierre Louis d’Epidémiologie et Santé Publique, Pierre et Marie Curie University, Paris, France
  6. 6Department of Rheumatology, Pitié-Salpêtrière Hospital, Paris, France
  1. Correspondence to Professor Cécile Gaujoux-Viala, Service de Rhumatologie, CHU de Nîmes Carémeau, Place du Professeur Robert Debré, 30029 Nîmes cedex 9, France; cecile.gaujoux.viala{at}


Background Although methotrexate (MTX) is the consensual first-line disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA), substantial heterogeneity remains with its prescription and dosage, which are often not optimal.

Objective To evaluate the symptomatic and structural impact of optimal MTX dose in patients with early RA in daily clinical practice over 2 years.

Methods Patients included in the early arthritis ESPOIR cohort who fulfilled the ACR-EULAR (American College of Rheumatology/European League against Rheumatism) criteria for RA and received MTX as a first DMARD were assessed. Optimal MTX dose was defined as ≥10 mg/week during the first 3 months, with escalation to ≥20 mg/week or 0.3 mg/kg/week at 6 months without Disease Activity Score in 28 joints remission. Symptomatic and structural efficacy with and without optimal MTX dose was assessed by generalised logistic regression with adjustment for appropriate variables.

Results Within the first year of follow-up, 314 patients (53%) with RA received MTX as a first DMARD (mean dose 12.2±3.8 mg/week). Only 26.4% (n=76) had optimal MTX dose. After adjustment, optimal versus non-optimal MTX dose was more efficient in achieving ACR-EULAR remission at 1 year (OR 4.28 (95% CI 1.86 to 9.86)) and normal functioning (Health Assessment Questionnaire ≤0.5; OR at 1 year 4.36 (95% CI 2.03 to 9.39)), with no effect on radiological progression. Results were similar during the second year.

Conclusion Optimal MTX dose is more efficacious than non-optimal dose for remission and function in early arthritis in daily practice, with no impact on radiological progression over 2 years.

  • Methotrexate
  • early rheumatoid arthritis

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  • Contributors CGV, MD, BC, BF: design of the study. CGV, NR: statistical analysis. CGV, MD, BC, BF, NR: interpretation of the results. CGV: drafting the work. MD, BC, BF, NR: revising the article. CGV, NR, MD, BC, BF: final approval of the version submitted.

  • Funding An unrestricted grant from Merck Sharp and Dohme (MSD) was allocated for the first 5 years of the ESPOIR cohort study. Two additional grants from INSERM supported part of the biological database. The French Society of Rheumatology, Pfizer, Abbvie and Roche-Chugai also supported the ESPOIR cohort study.

  • Competing interests CGV and BF have received honoraria from Nordic Pharma and Medac. MD has received research grants from Nordic Pharma. BC has received honoraria from Nordic Pharma.

  • Ethics approval The Ethics Committee of Montpellier, France (no. 020307).

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