Beyond Hyperferritinemia: Evaluating Ferritin as a Predictor of Advanced Therapy in Adult-Onset Still's Disease

Background: Ferritin is a hallmark biomarker of systemic inflammation in adult-onset Still's disease (AOSD), but its potential role in guiding escalation to advanced therapy has not been established. This study aimed to evaluate whether ferritin, alone or in combination with simple clinical variables, could predict the need for advanced therapy in AOSD. Methods: A retrospective review was conducted of 113 patients with AOSD fulfilling the Yamaguchi criteria at Chonnam National University Hospital. Baseline demographic, clinical, and laboratory data were collected at the index episode. The primary endpoint was defined as the use of advanced therapy-namely, intravenous immunoglobulin (IVIG), anakinra, or tocilizumab-during the index hospitalization. Ferritin was log-transformed and analyzed both as a continuous variable and in quartiles. A pragmatic Ferritin-Guided Escalation Rule (FGER) points score was constructed by combining ferritin quartiles with malignancy and ANA status. Logistic regression, Fisher's exact test, and bootstrapped receiver operating characteristic (ROC) analyses were applied. Results: The cohort was predominantly male (64.6%) with a mean age of 44.9 years. Median ferritin was 4626.6 µg/L (IQR 1169.3-14,239.8). Advanced therapy was required in 15 patients (13.3%), including 14 who received tocilizumab, 1 IVIG, and 1 anakinra. When stratified by ferritin quartiles, advanced therapy occurred in 10.7% of Q1, 21.4% of Q2, 10.7% of Q3, and 10.7% of Q4 patients. Comparison of Q4 versus Q1-Q3 yielded an odds ratio of 0.67 (p = 0.47). Discriminatory performance was poor for both continuous ferritin (AUC 0.49, 95% CI 0.30-0.68) and the FGER points score (AUC 0.51, 95% CI 0.32-0.71). Calibration analysis also demonstrated limited agreement between predicted and observed risks. Conclusions: In this retrospective cohort, ferritin-whether assessed continuously, by quartiles, or within a simple bedside score-did not predict the need for advanced therapy (IVIG, anakinra, or tocilizumab) in AOSD. Although advanced therapies were administered to 13.3% of patients, ferritin was not a reliable escalation biomarker.