Effect of Antifibrotic Use on Mortality in Patients with Idiopathic Pulmonary Fibrosis

被引:1
作者
Xu, Huiping [1 ]
Hui, Siu L. [1 ]
Lee, Joyce S. [3 ]
Zhang, Zuoyi [4 ]
Boente, Ryan D. [2 ]
机构
[1] Indiana Univ, Sch Med, Dept Biostat & Hlth Data Sci, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Div Pulm Crit Care Sleep & Occupat Med, Indianapolis, IN 46202 USA
[3] Univ Colorado Denver Anschutz Med Campus, Aurora, CO USA
[4] AbbVie Inc, N Chicago, IL USA
基金
美国国家卫生研究院;
关键词
antifibrotics; IPF; mortality; observational study; PROPENSITY SCORE; PIRFENIDONE; OUTCOMES; NINTEDANIB; SURVIVAL; UPDATE; COHORT; ADULTS;
D O I
10.1513/AnnalsATS.202312-1054OC
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Rationale: Observational studies report a significant protective effect of antifibrotics on mortality among patients with idiopathic pulmonary fibrosis (IPF). Many of these studies, however, were subject to immortal time bias because of the mishandling of delayed antifibrotic initiation. Objectives: To evaluate the antifibrotic effect on mortality among patients with IPF using appropriate statistical methods that avoid immortal time bias. Methods: Using a large administrative database, we identified 10,289 patients with IPF, of whom 2,300 used antifibrotics. Treating delayed antifibrotic initiation as a time-dependent variable, three statistical methods were used to control baseline characteristics and avoid immortal time bias. Stratified analysis was performed for patients who initiated antifibrotics early and those who initiated treatment late. For comparison, methods that mishandle immortal time bias were performed. A simulation study was conducted to demonstrate the performance of these models in a wide range of scenarios. Results: All three statistical methods yielded nonsignificant results for the antifibrotic effect on mortality, with the stratified analysis for patients with early antifibrotic initiation suggesting evidence for reduced mortality risk (for all patients, hazard ratio, 0.89; 95% confidence interval, 0.79-1.01; - 1.01; P = 0.08; for patients who were 65 years or older, hazard ratio, 0.85; 95% confidence interval, 0.73-0.98; - 0.98; P = 0.03). Methods that mishandle immortal time bias demonstrated significantly lower mortality risk for antifibrotic users. Bias of these methods was evident in the simulation study, where appropriate methods performed well with little to no bias. Conclusions: Findings in this study did not confirm an association between antifibrotics and mortality, with a stratified analysis showing support for a potential treatment effect with early treatment initiation.
引用
收藏
页码:1407 / 1415
页数:9
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