The Efficacy of Antifibrotics in Combined Pulmonary Fibrosis and Emphysema: A Nationwide Multicentre Retrospective Cohort Study

초록

Introduction: While efficacy of antifibrotics (pirfenidone and nintedanib) in idiopathic pulmonary fibrosis (IPF) is well established, its effects on combined pulmonary fibrosis and emphysema (CPFE) remain unclear. We evaluated the therapeutic efficacy of antifibrotics in CPFE patients. Methods: This multicentre study used the Korean IPF Cohort registry, identifying 966 CPFE patients. A 6-month landmark window controlled for immortal time bias. Propensity score matching (PSM) balanced baseline characteristics for age, sex, body mass index (BMI), lung cancer, and Composite Physiologic Index (CPI). Post-matching survival outcomes (N = 584) were evaluated via 100-month truncated Restricted Mean Survival Time (RMST) to account for proportional hazards violation. Annual longitudinal lung function trajectories (n = 310) were estimated via piecewise linear mixed models (LMM) handling missing data as missing at random. Results: In the matched cohort, conventional Cox analysis exhibited a marginally significant risk in the treatment arm (HR = 1.29; 95% CI: 1.01–1.65; p = 0.045); however, a distinct trajectory cross-over occurred at ∼100 months. Truncated RMST confirmed that the net survival difference was statistically equivalent (−6.87 months; 95% CI: −14.64 to 0.90; p = 0.264). Conversely, a significant physiological benefit was demonstrated in continuous lung function preservation, markedly attenuating the annual rate of diffusing capacity of the lung for carbon monoxide (DLCO) % predicted decline from −4.19 ± 0.37%/year pre-treatment to −2.97 ± 0.30%/year post-treatment (p < 0.001). Conclusions: Although antifibrotic therapy does not demonstrate a long-term average survival advantage over a decade, it significantly attenuates the longitudinal physiological decline of lung function (DLCO) in patients with CPFE, providing a protective brake against disease progression. © 2026 The Author(s)

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