title: Evaluating relationships between symptom duration and persistence of rheumatoid arthritis: does a window of opportunity exist? Results on the Leiden early arthritis clinic and ESPOIR cohorts.
abstract: BACKGROUND
  A prolonged symptom or disease duration at treatment initiation is associated with unfavourable outcomes in rheumatoid arthritis (RA). It is unknown whether this relation is linear, referring to a common 'the-earlier-the-better principle', or whether a transient time frame in which the disease is more susceptible to treatment exists, referring to a 'window of opportunity'. To elucidate this, we evaluated the shape of the associations of symptom duration with persistence of RA.
  
  
  METHODS
  Patients with 1987 RA treated with disease modifying antirheumatic drugs (DMARDs) in the Leiden Early Arthritis Clinic (EAC, n=738) and Evaluation et Suivi de POlyarthrites Indifférenciées Récentes (ESPOIR) (n=533) were studied. Cox proportional hazards regression models using natural cubic splines were performed; the log-HR on DMARD-free sustained remission (the opposite of RA persistence) during 5-year follow-up was plotted against symptom duration. Discrimination was measured using time-dependent receiver operator characteristic curves. Subanalyses were performed stratified for the DMARDs used (methotrexate or other conventional DMARDs) and for anticitrullinated peptide antibody (ACPA).
  
  
  RESULTS
  11.5% (85/738) and 5.4% (29/533) of EAC and ESPOIR RA patients achieved DMARD-free sustained remission. In both cohorts and all analyses, the curves depicting the log-HRs on remission in relation to symptom duration were not linear. The symptom duration with optimal discriminative ability was 14.9 weeks (95% CI 12.3 to 16.0; area under the curve (AUC) 0.61) in the EAC and 19.1 weeks (95% CI 12.3 to 28.0; AUC 0.59) in ESPOIR. For ACPA-positive RA, this was 11.4 weeks (95% CI 7.7 to 79.0; AUC 0.56) and for ACPA-negative RA 15.0 weeks (95% CI 9.7 to 48.7; AUC 0.56).
  
  
  CONCLUSIONS
  The association between symptom duration and RA persistence is not linear, suggesting the presence of a confined period in which RA is more susceptible to treatment.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J A B
authors.initials: JA
authors.lastname: van Nies
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Tsonaka
authors.affiliation: Department of Rheumatology, Nîmes University Hospital, EA 2415, Montpellier I University, Nîmes, France.
authors.forename: C
authors.initials: C
authors.lastname: Gaujoux-Viala
authors.affiliation: Université Pierre et Marie Curie Curie-Paris 6, GRC08, Institut Pierre Louis d'Epidémiologie et Santé Publiqu, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Fautrel
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A H M
authors.initials: AH
authors.lastname: van der Helm-van Mil
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D016016:Proportional Hazards Models; D012074:Remission Induction; D012460:Sulfasalazine / Q000627:therapeutic use; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D007555:Isoxazoles; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012460:Sulfasalazine; D006886:Hydroxychloroquine; D000077339:Leflunomide; D008727:Methotrexate
keywords: Early Rheumatoid Arthritis; Epidemiology; Outcomes research