Is Referring Early Arthritis Patients within 6 Weeks Associated with Better Long-Term Outcomes than Referring within 12 Weeks after Symptom Onset? – Investigating the Evidence for the First EULAR Recommendation for Early Arthritis

Background: EULAR-recommendations for management of early arthritis formulated that patients should be referred to, and seen by a rheumatologist, within 6-weeks after symptom onset. Because implementation provides challenges, and evidence supporting that referral ≤6 weeks is better than e.g. <12-weeks is missing, we investigated if ≤6-weeks relates to improved long-term outcomes, measured with sustained DMARD-free remission (SDFR) and radiographic progression. Methods: Consecutive 1987-RA patients of the Leiden EAC (n=1025) and ESPOIR (n=514) were studied during median 7 and 10 years follow-up. Patients were categorized on duration between symptom onset and first encounter with a rheumatologist; ≤6, 7-12, and >12-weeks. Multivariable Cox regression (SDFR), linear mixed models (radiographic progression), and meta-analyses were used. Findings: Leiden RA-patients encountered the rheumatologist within 6-weeks obtained SDFR more often than patients seen within 7-12-weeks (HR 1·59, 95%CI:1·02-2·49), and >12-weeks (HR 1·54, 95%CI:1·04-2·29). In ESPOIR, similar but non-significant effects were observed; meta-analysis showed that within 6-weeks was better than 7-12-weeks (HR 1·69, 95%CI:1·10-2·57) and >12-weeks (HR 1·67, 95%CI:1·08-2·58). Patients encountered the rheumatologist within 6-weeks had similar radiographic progression than those seen 7-12-weeks, in any cohort, or meta-analysis. Interpretation: Scientific evidence underlying the first EULAR recommendation depends on the outcome of interest; visiting a rheumatologist within 6-weeks of symptom-onset had clear benefits for achieving SDFR, but not for radiographic progression. Funding Statement: EAC was supported by the European Research Council (ERC-Starting grant, No714312) and the Dutch Arthritis Society. ESPOIR was funded by an unrestricted grant from Merck Sharp and Dohme (MSD) for the first 5 years. Additionally, two INSERM grants, The French Society of Rheumatology, Pfizer, Abbvie, Lilly, and Sanofi supported ESPOIR. Declaration of Interests: The authors stated: "None." Ethics Approval Statement: Written informed consent was obtained by all participants and both cohorts received approval by their ethical committees.