Background: The first recommendation of the European League Against Rheumatism for the management of early arthritis states that patients should be referred to, and seen by, a rheumatologist within 6 weeks after symptom onset. However, implementation of this recommendation is a challenge, and evidence supporting this timeframe compared with longer timeframes is absent. Therefore, we aimed to investigate whether visiting a rheumatologist within 6 weeks of symptom onset relates to improved long-term outcomes compared with visiting a rheumatologist between 7 and 12 weeks after symptom onset. Methods: In this observation cohort study, consecutive patients with rheumatoid arthritis from the Leiden Early Arthritis Clinic (EAC) and the French Etude et Suivi des Polyarthrites Indifferenciées Recentes (ESPOIR) were included. In this analysis, we included patients who were diagnosed with rheumatoid arthritis and classified according to 1987 American College of Rheumatology criteria, and with symptom onset and remission data available. Patients were categorised into groups based on time between symptom onset and first encounter with a rheumatologist: within 6 weeks, between 7 weeks and 12 weeks, and after 12 weeks. The main outcomes were sustained disease-modifying antirheumatic drug (DMARD)-free remission and radiographic progression. Multivariable Cox regression, linear mixed models, and meta-analyses were used. Findings: 1025 patients with rheumatoid arthritis included in the EAC between Jan 1, 1996, and Dec 31, 2017, and 514 patients with rheumatoid arthritis included in ESPOIR between Nov 1, 2002, and April 30, 2005, were included in this analysis. Median follow-up was 7·1 years (IQR 3·9–12·2) in the EAC and 10·0 years (9·0–10·0) in ESPOIR. After 7 years of follow-up in the EAC, 30 (24%) of 127 patients with a time to encounter of 6 weeks or less, 45 (20%) of 223 patients with a time of 7–12 weeks, and 100 (15%) of 675 patients with a time of more than 12 weeks achieved sustained DMARD-free remission. After 10 years of follow-up in ESPOIR, three (27%) of 11 patients with a time to encounter of 6 weeks or less, 11 (11%) of 100 patients with a time of 7–12 weeks, and 41 (10%) of 403 patients with a time of more than 12 weeks had sustained DMARD-free remission. In the EAC multivariable analysis, patients who encountered a rheumatologist within 6 weeks obtained sustained DMARD-free remission more often than those seen between 7 and 12 weeks (hazard ratio [HR] 1·59 [95% CI 1·02–2·49], p=0·042), and after 12 weeks (1·54 [1·04–2·29], p=0·032). In the ESPOIR multivariable analysis, similar but non-significant effects were observed (HR 2·81 [95% CI 0·75–10·53], p=0·12, for within 6 weeks vs 7–12 weeks and 3·05 [0·89–10·49], p=0·077, for within 6 weeks vs more than 12 weeks). The meta-analysis of both cohorts showed that the time to encounter of 6 weeks or less was associated with a higher chance of achieving sustained DMARD-free remission than a time of 7–12 weeks (HR 1·69 [95% CI 1·10–2·57], p=0·016) and a time of more than 12 weeks (1·67 [1·08–2·58], p=0·020). The multivariable analysis showed that patients who encountered a rheumatologist within 6 weeks had similar radiographic progression to those seen between 7 and 12 weeks in both cohorts (β=1·00 [95% CI 0·95–1·05], p=0·96, in the EAC and 0·93 [0·80–1·07], p=0·30, in ESPOIR) and to those seen after 12 weeks (β=0·96 [95% CI 0·92–1·00], p=0·064, in the EAC and 0·89 [0·77–1·02], p=0·10, in ESPOIR). In the meta-analysis, a time to encounter of 6 weeks or less was not associated with less radiographic progression than a time of 7–12 weeks (β=0·99 [95% CI 0·95–1·04], p=0·75) but was associated with less radiographic progression than a time of more than 12 weeks (0·95 [0·91–0·99], p=0·028). Interpretation: Visiting a rheumatologist within 6 weeks of symptom onset had benefits for achieving sustained DMARD-free remission, but not for radiographic progression. Funding: European Research Council, Dutch Arthritis Society, Merck Sharp & Dohme, INSERM, The French Society of Rheumatology, Pfizer, AbbVie, Lilly, and Sanofi.

Additional Metadata
Persistent URL dx.doi.org/10.1016/S2665-9913(20)30061-8, hdl.handle.net/1765/127024
Journal The Lancet Rheumatology
Citation
Niemantsverdriet, E. (Ellis), Dougados, M, Combe, B, & van der Helm-van Mil, A.H.M. (2020). Referring early arthritis patients within 6 weeks versus 12 weeks after symptom onset: an observational cohort study. The Lancet Rheumatology. doi:10.1016/S2665-9913(20)30061-8