Is Earlier Always Better? Timing of Antifibrotic Therapy and Overall Survival in Idiopathic Pulmonary Fibrosis: a Multicenter Retrospective Study

Background Antifibrotic therapies slow functional decline and improve survival in patients with idiopathic pulmonary fibrosis (IPF). Although early initiation is generally recommended, the optimal timing of treatment in real-world clinical practice remains uncertain. In particular, the relationship between the interval from diagnosis to treatment initiation and overall survival (OS), as well as the clinical implications of physician-judged deferred initiation, have not been fully clarified. Methods This multicenter retrospective cohort study included 150 patients diagnosed with IPF between April 2021 and March 2023 who received antifibrotic therapy. Treatment timing was evaluated using two definitions: 1) objectively defined intervals from diagnosis of IPF to treatment initiation (0–180, 181–364, and ≥ 365 days); and 2) physician-judged deferred initiation documented in medical records, defined as a clinician‑guided postponement based on clinical, patient‑related, or contextual considerations. The primary endpoint was OS. Landmark analyses were performed at 180 and 365 days to reduce immortal time bias. Survival outcomes were analyzed using the Kaplan–Meier method and Cox proportional hazards regression models. Multivariable analyses were used to adjust for relevant clinical covariates. In addition, reasons for delayed treatment initiation were examined. Results Among the 150 patients, longer diagnosis-to-treatment intervals were associated with longer OS in the landmark analyses. In contrast, patients with physician-judged deferred initiation showed no significant difference in OS (log-rank p = 0.164), although physician-judged deferred initiation was independently associated with OS in the multivariable analysis. In the multivariable analysis, older age, lower percent predicted forced vital capacity (%forced vital capacity), and a longer interval from referral to IPF diagnosis were also independently associated with OS. The most common reasons for delayed initiation included minimal or stable symptoms, concerns regarding adverse effects, and diagnostic uncertainty. Conclusions Physician‑judged deferred initiation was independently associated with OS, likely reflecting underlying disease activity and clinical risk stratification rather than a direct causal effect of postponing therapy. These findings underscore the limitations of evaluating treatment timing solely by elapsed time and emphasize the importance of early diagnosis, timely referral to specialized centers, and individualized clinical decision-making in the management of IPF. Clinical trial registration Not applicable.