Earlier Time-to-Referral Predicts Increased Likelihood of Achieving DMARD-Free Remission in Rheumatoid Arthritis

Unrecognizable man with pain in his hand talks with an unrecognizable female doctor.
Researchers investigated the association between rheumatologist visits within 6 weeks of symptom onset and improved long-term disease outcomes in rheumatoid arthritis.

Rheumatologist visits within 6 weeks of symptom onset was associated with greater likelihood of sustained disease-modifying antirheumatic drug (DMARD)-free remission in patients with early rheumatoid arthritis (RA), according to study results published in Lancet Rheumatology.

This observational study enrolled patients with RA from 2 existing cohort studies, including the Leiden Early Arthritis Clinic (EAC) and the French Etude et Suivi des Polyarthrites Indifferenciées Recentes (ESPOIR). Patients with available symptom onset and remission data were eligible for inclusion in the study. In the present analysis, patients were categorized into 3 groups based on time between symptom onset and first encounter with a rheumatologist: within 6 weeks; within 7 to 12 weeks; and after 12 weeks. The primary outcome was sustained DMARD-free remission, identified from EAC and ESPOIR records. Radiographic progression was also assessed. Multivariable Cox regression was used to assess the relationship between time-to-referral and DMARD-free remission. Models were adjusted for relevant demographic and clinical characteristics, including age, sex, erythrocyte sedimentation rate, swollen joint count, and anti-citrullinated protein antibodies.

The present analysis included 1025 patients from the EAC and 514 patients from the ESPOIR. Mean follow-up time was 7.1 years (interquartile range [IQR], 3.9-12.2 years) and 10.0 years (IQR, 9.0-10.0 years) in the EAC and ESPOIR, respectively. After 7 years of follow-up in the EAC, DMARD-free remission was achieved by 30 (24%) of 127 patients with a time to encounter of ≤6 weeks, 45 (20%) of 223 patients with a time of 7 to 12 weeks, and 100 (15%) of 675 patients with a time of >12 weeks. After 10 years of follow-up in the ESPOIR, sustained DMARD-free remission was achieved by 3 (27%) of 11 patients with a time to encounter of ≤6 weeks, 11 (11%) of 100 patients with a time of 7 to 12 weeks, and 41 (10%) of 403 patients with a time of >12 weeks.

According to Cox regression models for the EAC cohort, patients who encountered a rheumatologist within 6 weeks of symptom onset were significantly more likely to achieve sustained DMARD-free remission than patients with a time of 7 to 12 weeks (hazard ratio [HR], 1.59; 95% CI, 1.02-2.49; P =.042) and >12 weeks (HR, 1.54; 95% CI, 1.04-2.29; P =.032). Similar trends were observed in the ESPOIR cohort, though results were not statistically significant. Results from pooled analyses showed that , there was a greater likelihood of achieving DMARD-free sustained remission with a time to encounter of ≤6 weeks than a time of 7 to 12 weeks (HR, 1.69; 95% CI, 1.10-2.57; P =.016) and >12 weeks (HR, 1.67; 95% CI, 1.08-2.58; P =.020). In both the EAC and ESPOIR cohorts, patients who visited a rheumatologist within 6 weeks had similar radiographic progression compared with patients in the other time-to-encounter strata.

These data suggest that early referral to a rheumatologist was associated with achieving sustained DMARD-free remission; however, early referral did not significantly affect radiographic progression.

As study limitations, investigators noted that symptom onset was patient-reported rather than defined by a validated symptom scale. As such, significant heterogeneity may likely exist in the definition of “symptom onset.”

“[A]chieving a time to encounter within 6 weeks, although challenging, might become of increasing importance,” the investigators wrote.


Niemantsverdriet E, Dougados M, Combe B, van der Helm-van Mil AHM. Referring early arthritis patients within 6 weeks versus 12 weeks after symptom onset: an observational cohort study [published online April 28, 2020]. Lancet Rheumatol. doi:10.1016/S2665-9913(20)30061-8