Impact of etanercept on the progression of undifferentiated arthritis to rheumatoid arthritis

This study explores the association between tumor necrosis factor (TNF) antagonist therapy and the progression from undifferentiated arthritis (UA) to rheumatoid arthritis (RA). This single-center prospective observational real-world study enrolled 70 patients with UA (baseline score ≥ 8) at Xingtai People’s Hospital (May–December 2020). After propensity score matching (1:1), 64 patients were matched; 4 lost to follow-up were excluded, leaving 60 for final analysis. Patients received MTX monotherapy or etanercept + MTX. Between-group differences were assessed using the Mann–Whitney U test, chi-square test, or Fisher exact test. Survival was analyzed using Kaplan–Meier curves and log-rank tests, and independent prognostic factors were identified through multivariable Cox regression. A total of 60 patients (30 per group) were included in the final analysis. During the 3-year follow-up, patients in the etanercept + MTX group had a significantly lower risk of progression to RA compared with the MTX monotherapy group (6/30 [20.0%] vs 14/30 [46.7%]; log-rank P  = .012). After adjusting for potential confounders, combination therapy remained independently associated with reduced progression risk (HR = 0.28, 95% CI: 0.10–0.83, P  = .022). Clinical remission at 3 years was achieved in 25 of 30 patients (83.3%) in the combination group, compared to 17 of 30 (56.7%) in the monotherapy group ( P  = .024). In this exploratory real-world observational study, initial treatment with etanercept + MTX was associated with a lower observed risk of progression to RA and a higher observed rate of clinical remission than MTX monotherapy in high-risk UA patients. These findings should be considered hypothesis-generating and require confirmation in adequately powered randomized controlled trials in diverse populations.