Predictors of good response to conventional synthetic DMARDs in early seronegative rheumatoid arthritis: data from the ESPOIR cohort

Arthritis Res Ther. 2019 Nov 15;21(1):243. doi: 10.1186/s13075-019-2020-x.


Background and objective: Early seronegative rheumatoid arthritis (RA) is considered a specific entity, especially regarding diagnostic issues and prognosis. Little is known about its potentially different initial clinical presentation and outcome. We aimed to determine predictors of good response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in seronegative RA patients with early inflammatory arthritis.

Patients and methods: Patients from the ESPOIR cohort with early inflammatory arthritis fulfilling the 2010 ACR/EULAR classification criteria for RA despite negativity for both rheumatoid factor and anti-CCP antibodies. The primary endpoint was a good or moderate EULAR response assessed after 1 year of follow-up, given at least 3 months of treatment with a csDMARD. Secondary objectives were to compare the early therapeutic response to methotrexate (MTX) and leflunomide (LEF) versus other csDMARDs (hydroxychloroquine, sulfasalazine) and to identify factors associated with functional disability (Health Assessment Questionnaire-Disability Index [HAQ-DI] > 0.5 at 1 year) and structural progression (van der Heijde-modified total Sharp score > 1 and > 5 points at 1 year). Logistic regression analysis was used to determine independent predictors of outcomes.

Results: One hundred seventy-two patients were analyzed. Overall, 98/172 (57%) patients received MTX during the first year of follow-up. A good or moderate EULAR response at 1 year was associated with early use of csDMARDs (i.e., within 3 months after the first joint swelling) on univariate and multivariable analysis (odds ratio = 2.41 [95% confidence interval 1.07-5.42], p = 0.03). Response rates were not affected by other classical prognostic factors (i.e., baseline DAS28). Presence of erosions at baseline was associated with Sharp score progression > 1 point and > 5 points (both p = 0.03) at 1 year. HAQ-DI ≥ 1 at inclusion and active smoking were significantly associated with HAQ-DI > 0.5 at 1 year.

Conclusion: Our results suggest that delay in initiation of csDMARD more than baseline clinical, biological, or imaging features predominantly affects the outcome in early seronegative RA. These findings confirm that the usual therapeutic concepts in RA (early treatment, tight control, and treat-to-target) should be applied similarly to both seropositive and seronegative disease forms.

Trial registration: NCT03666091. Registered September 11, 2018.

Keywords: DMARD; ESPOIR cohort; Rheumatoid arthritis; Seronegative.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Citrullinated Protein Antibodies / blood
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Cohort Studies
  • Disability Evaluation
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Immunosuppressive Agents / therapeutic use
  • Leflunomide / therapeutic use*
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Prognosis
  • Rheumatoid Factor / blood
  • Sulfasalazine / therapeutic use
  • Surveys and Questionnaires
  • Treatment Outcome


  • Anti-Citrullinated Protein Antibodies
  • Antirheumatic Agents
  • Immunosuppressive Agents
  • Sulfasalazine
  • Hydroxychloroquine
  • Rheumatoid Factor
  • Leflunomide
  • Methotrexate

Associated data