Clinical predictors of Relapse-free survival in early pulmonary sarcoidosis

Abstract

Relapse remains a major challenge in the long-term management of pulmonary sarcoidosis, yet predictors of relapse-free survival in patients with early-stage disease are incompletely understood. We investigated the clinical determinants of time to relapse in a biopsy-confirmed cohort of patients with pulmonary sarcoidosis followed for up to 15 years. Methods: This retrospective cohort study included 200 adults (mean age 42.0 ± 11.2 years, 72.0% women) with biopsy-confirmed Stage I–II pulmonary sarcoidosis. The primary outcome was relapse requiring re-initiation or escalation of systemic therapy after remission. Relapse-free survival was evaluated using Kaplan–Meier analysis and compared by the log-rank test. Cox proportional hazards models were used to identify independent predictors of relapse. Results: During long-term follow-up, 36 patients (18.0%) experienced disease relapse. Relapse-free survival was significantly lower among patients who received systemic treatment at baseline than among untreated patients (log-rank p < 0.001). In multivariable Cox analysis, baseline systemic treatment (adjusted hazard ratio [HR] 4.27, 95% confidence interval [CI] 1.39–13.09; p = 0.011) and Scadding Stage II disease (HR 2.58, 95% CI 1.26–5.29; p = 0.010) independently predicted relapse. Increasing age was associated with a lower relapse risk (HR 0.70 per 10-year increase, 95% CI 0.50–1.00; p = 0.047). Baseline FVC and sex were not independently associated with relapse, while extrapulmonary involvement showed a borderline association (HR 2.16, 95% CI 0.97–4.80; p = 0.059). Conclusions: Long-term relapse-free survival in early pulmonary sarcoidosis is primarily determined by baseline disease phenotype. Stage II disease identifies patients at increased relapse risk, whereas the association between systemic treatment and relapse most likely reflects confounding by indication rather than a detrimental treatment effect. Time-to-event analysis provides a clinically relevant framework for long-term risk stratification in early-stage sarcoidosis.