Supplementary Material for: Efficacy and Safety of Pirfenidone in Advanced Idiopathic Pulmonary Fibrosis

<b><i>Background:</i></b> Although phase 3 trials showed significant efficacy and acceptable safety profiles for pirfenidone in mild-to-moderate idiopathic pulmonary fibrosis (IPF), data on advanced IPF are limited. <b><i>Objectives:</i></b> The study aimed to evaluate the efficacy and safety of pirfenidone in advanced IPF patients. <b><i>Methods:</i></b> The clinical data of 138 IPF patients (advanced group: 27%) treated with pirfenidone were retrospectively reviewed and compared between advanced and non-advanced groups. Advanced IPF was defined as (1) forced vital capacity (FVC) &lt; 50% predicted or (2) diffusing capacity for carbon monoxide &lt; 30% predicted. <b><i>Results:</i></b> The mean treatment duration was 51.3 weeks, and lung function analysis was performed in 81 patients (17 in the advanced group). Changes in FVC and total lung capacity (TLC) were significantly reduced at 6 months after treatment in both the advanced (ΔFVC [6 months]: –6.3 [before] vs. 0.7% predicted [after]; ΔTLC: –5.3 vs. 0.8) and non-advanced (ΔFVC: –3.4 vs. 0.5; ΔTLC: –3.1 vs. –0.9) groups. The rate of decline in FVC and TLC was significant before treatment, but not after treatment in the advanced (FVC: –1.27 [before] vs. 0.21% predicted/month [after]; TLC: –0.89 vs. –0.15) and non-advanced (FVC: –0.60 vs. –0.20; TLC: –0.54 vs. –0.17) groups. The advanced group showed a similar rate of adverse events (AEs) (78.4 vs. 88.1%, <i>p</i> = 0.270), but more serious AEs (40.5 vs. 10.9%, <i>p</i> &lt; 0.001) including death (24.3 vs. 5.0%, <i>p</i> = 0.002). <b><i>Conclusions:</i></b> In advanced IPF, pirfenidone showed similar efficacy and safety to non-advanced IPF except for serious AEs, which may be due to the advanced status itself.

<b><i>背景：</i></b> 尽管III期临床试验显示吡非尼酮（pirfenidone）在轻中度特发性肺纤维化（idiopathic pulmonary fibrosis, IPF）中具有显著疗效且安全性可接受，但针对晚期IPF的相关数据仍较为有限。<b><i>研究目的：</i></b> 本研究旨在评估吡非尼酮用于晚期IPF患者的疗效与安全性。<b><i>研究方法：</i></b> 本研究回顾性分析了138例接受吡非尼酮治疗的IPF患者的临床资料，其中晚期患者占总入组人数的27%，并按晚期与非晚期分组进行对比。晚期IPF的定义为以下任一情况：(1) 用力肺活量（forced vital capacity, FVC）占预计值百分比<50%；或(2) 一氧化碳弥散量（diffusing capacity for carbon monoxide）占预计值百分比<30%。<b><i>研究结果：</i></b> 本研究的平均治疗时长为51.3周，共对81例患者进行了肺功能分析（其中晚期组17例）。治疗6个月后，晚期组与非晚期组的FVC及肺总量（total lung capacity, TLC）变化均显著降低：晚期组ΔFVC（6个月）：治疗前-6.3%预计值 vs 治疗后0.7%预计值；ΔTLC：-5.3% vs 0.8%。非晚期组ΔFVC：-3.4% vs 0.5%；ΔTLC：-3.1% vs -0.9%。两组的FVC及TLC下降速率在治疗前均较为显著，但治疗后不再明显：晚期组FVC：-1.27%预计值/月（治疗前）vs 0.21%预计值/月（治疗后）；TLC：-0.89% vs -0.15%。非晚期组FVC：-0.60% vs -0.20%；TLC：-0.54% vs -0.17%。晚期组的不良事件（adverse events, AEs）发生率与非晚期组相近（78.4% vs 88.1%，<i>p</i>=0.270），但严重不良事件发生率更高（40.5% vs 10.9%，<i>p</i><0.001），其中包括死亡事件（24.3% vs 5.0%，<i>p</i>=0.002）。<b><i>研究结论：</i></b> 对于晚期IPF患者，吡非尼酮的疗效与安全性与非晚期IPF患者基本一致，仅严重不良事件发生率更高，这一差异可能与患者本身的晚期疾病状态有关。