PDF(Pubmed)
Abstract：
OBJECTIVE: Pooled analyses of previous randomized controlled trials reported that antifibrotics improved survival in patients with idiopathic pulmonary fibrosis (IPF), but the results were only based on short-term outcome data from selected patients who met strict criteria. Observational studies/meta-analyses also suggested that antifibrotics improve survival, but these studies failed to control for immortal time bias that considerably exaggerates drug effects. Therefore, whether antifibrotics truly improve long-term survival in patients with IPF in the real world remains undetermined and requires external validity.
METHODS: We used data from the Japanese National Claims Database to estimate the intention-to-treat effect of antifibrotics on mortality. To address immortal time bias, we employed models treating antifibrotic initiation as a time-dependent covariate and target trial emulation (TTE), both incorporating new-user designs for antifibrotics and treating lung transplantation as a competing event.
RESULTS: Of 30,154 patients with IPF, 14,525 received antifibrotics. Multivariate Fine-Gray models with antifibrotic initiation as a time-dependent covariate revealed that compared with no treatment, nintedanib (adjusted hazard ratio [aHR], 0.85; 95% confidence interval [CI], 0.81-0.89) and pirfenidone (aHR, 0.89; 95% CI, 0.86-0.93) were associated with reduced mortality. The TTE model also replicated the associations of nintedanib (aHR, 0.69; 95% CI, 0.65-0.74) and pirfenidone (aHR, 0.81; 95% CI, 0.78-0.85) with reduced mortality. Subgroup analyses confirmed this association regardless of age, sex, and comorbidities, excluding certain subpopulations.
CONCLUSIONS: The results of this large-scale real-world analysis support the generalizability of the association between antifibrotics and improved survival in various IPF populations.
METHODS: We used data from the Japanese National Claims Database to estimate the intention-to-treat effect of antifibrotics on mortality. To address immortal time bias, we employed models treating antifibrotic initiation as a time-dependent covariate and target trial emulation (TTE), both incorporating new-user designs for antifibrotics and treating lung transplantation as a competing event.
RESULTS: Of 30,154 patients with IPF, 14,525 received antifibrotics. Multivariate Fine-Gray models with antifibrotic initiation as a time-dependent covariate revealed that compared with no treatment, nintedanib (adjusted hazard ratio [aHR], 0.85; 95% confidence interval [CI], 0.81-0.89) and pirfenidone (aHR, 0.89; 95% CI, 0.86-0.93) were associated with reduced mortality. The TTE model also replicated the associations of nintedanib (aHR, 0.69; 95% CI, 0.65-0.74) and pirfenidone (aHR, 0.81; 95% CI, 0.78-0.85) with reduced mortality. Subgroup analyses confirmed this association regardless of age, sex, and comorbidities, excluding certain subpopulations.
CONCLUSIONS: The results of this large-scale real-world analysis support the generalizability of the association between antifibrotics and improved survival in various IPF populations.
摘要：
目的：先前随机对照试验的汇总分析报告，抗纤维化药物可改善特发性肺纤维化（IPF）患者的生存率，但结果仅基于符合严格标准的选定患者的短期结局数据.观察性研究/荟萃分析还表明，抗纤维化药物可改善生存率，但是这些研究未能控制不朽的时间偏差，这大大夸大了药物的作用。因此,在现实世界中,抗纤维化药物是否真正改善IPF患者的长期生存率仍未确定,需要外部有效性.
方法：我们使用日本国家索赔数据库的数据来评估抗纤维化药物对死亡率的意向治疗效果。为了解决不朽的时间偏见，我们采用抗纤维化起始治疗的模型作为时间依赖性协变量和目标试验仿真（TTE），两者都纳入了抗纤维化药物的新用户设计，并将肺移植作为竞争事件进行治疗。
结果：在30,154名IPF患者中，14,525接受抗纤维化药物治疗。以抗纤维化起始为时间依赖性协变量的多变量Fine-Gray模型显示，与不治疗相比，尼达尼布(调整后的危险比[AHR]，0.85；95%置信区间[CI]，0.81-0.89)和吡非尼酮(AHR，0.89；95%CI，0.86-0.93）与死亡率降低相关。TTE模型还复制了尼达尼布(AHR，0.69；95%CI，0.65-0.74)和吡非尼酮(AHR，0.81；95%CI，0.78-0.85），死亡率降低。亚组分析证实了这种关联，无论年龄，性别,和合并症，排除某些亚群。
结论：这一大规模现实世界分析的结果支持抗纤维化药物与不同IPF人群生存率改善之间的关系的普遍性。
方法：我们使用日本国家索赔数据库的数据来评估抗纤维化药物对死亡率的意向治疗效果。为了解决不朽的时间偏见，我们采用抗纤维化起始治疗的模型作为时间依赖性协变量和目标试验仿真（TTE），两者都纳入了抗纤维化药物的新用户设计，并将肺移植作为竞争事件进行治疗。
结果：在30,154名IPF患者中，14,525接受抗纤维化药物治疗。以抗纤维化起始为时间依赖性协变量的多变量Fine-Gray模型显示，与不治疗相比，尼达尼布(调整后的危险比[AHR]，0.85；95%置信区间[CI]，0.81-0.89)和吡非尼酮(AHR，0.89；95%CI，0.86-0.93）与死亡率降低相关。TTE模型还复制了尼达尼布(AHR，0.69；95%CI，0.65-0.74)和吡非尼酮(AHR，0.81；95%CI，0.78-0.85），死亡率降低。亚组分析证实了这种关联，无论年龄，性别,和合并症，排除某些亚群。
结论：这一大规模现实世界分析的结果支持抗纤维化药物与不同IPF人群生存率改善之间的关系的普遍性。
