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.
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.
['van Nies|J A B|JA|', 'Tsonaka|R|R|', 'Gaujoux-Viala|C|C|', 'Fautrel|B|B|', 'van der Helm-van Mil|A H M|AH|']
D000328:Adult D000368:Aged D018501:Antirheumatic Agents D019540:Area Under Curve D001172:Arthritis, Rheumatoid D001323:Autoantibodies D015331:Cohort Studies D018450:Disease Progression D005260:Female D006801:Humans D006886:Hydroxychloroquine D007555:Isoxazoles D000077339:Leflunomide D008297:Male D008727:Methotrexate D008875:Middle Aged D010456:Peptides, Cyclic D016016:Proportional Hazards Models D012074:Remission Induction D012460:Sulfasalazine D061665:Time-to-Treatment D016896:Treatment Outcome
Early Rheumatoid Arthritis Epidemiology Outcomes research