BACKGROUND Idiopathic pulmonary fibrosis (IPF) carries a high risk of lung cancer, but the effect of pirfenidone on lung cancer development remains uncertain. We investigated the association between pirfenidone use and lung cancer development in patients with IPF. METHODS We included 10 084 patients with IPF from the national claims database. Propensity score analysis with inverse probability of treatment weighting (IPTW) and landmark analyses were employed to evaluate lung cancer occurrence according to pirfenidone use. The association was evaluated using Cox regression models adjusted for clinical and socioeconomic variables. A single-center IPF clinical cohort (n=941) was used for validating the findings. RESULTS The mean patient age was 69.4 years, 73.8% were men, and 31.6% received pirfenidone. Lung cancer developed in 766 patients with IPF (7.6%; 21.9 cases per 1000 person-years) during a median follow-up of 3.0 years. After IPTW, the pirfenidone group showed lower incidence (10.4 versus 27.9 cases per 1000 person-years) than the no-pirfenidone group. Landmark analysis at 6 months after IPF diagnosis also showed lower incidence of lung cancer in the pirfenidone group than in the no-pirfenidone group. Pirfenidone use was independently associated with a reduced lung cancer risk (weighted adjusted hazard ratio [HR]: 0.347; 95% confidence interval [CI]: 0.258-0.466). A clinical cohort showed similar association (weighted adjusted HR: 0.716; 95% CI: 0.517-0.991). The association persisted across subgroups defined by age or sex. CONCLUSION Pirfenidone use may be associated with a reduced lung cancer risk in patients with IPF.

中文翻译：

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吡非尼酮和 IPF 中肺癌发展的风险：一项基于人群的全国性研究。


背景特发性肺纤维化 （IPF） 具有较高的肺癌风险，但吡非尼酮对肺癌发展的影响仍不确定。我们调查了吡非尼酮使用与 IPF 患者肺癌发展之间的关联。方法 我们从国家索赔数据库中纳入了 10 084 例 IPF 患者。采用具有治疗加权逆概率 （IPTW） 的倾向评分分析和标志分析来根据吡非尼酮的使用评估肺癌的发生。使用针对临床和社会经济变量进行调整的 Cox 回归模型评估相关性。使用单中心 IPF 临床队列 （n=941） 验证结果。结果 患者平均年龄为 69.4 岁，男性占 73.8%，接受吡非尼酮治疗的占 31.6%。在中位随访 3.0 年期间，766 名 IPF 患者 （7.6%;21.9 例/1000 人年） 发生肺癌。IPTW 后，吡非尼酮组的发病率低于无吡非尼酮组（10.4 例/1000 人年 vs 27.9 例/1000 人年）。IPF 诊断后 6 个月的标志性分析也显示吡非尼酮组的肺癌发病率低于非吡非尼酮组。吡非尼酮的使用与肺癌风险降低独立相关 （加权调整风险比 [HR]： 0.347;95% 置信区间 [CI]： 0.258-0.466）。一个临床队列显示类似的关联 （加权调整 HR： 0.716;95% CI： 0.517-0.991）。这种关联在由年龄或性别定义的亚组中持续存在。结论 吡非尼酮的使用可能与 IPF 患者肺癌风险降低有关。