Ley Brett, Swigris Jeffrey, Day Bann-Mo, Stauffer John L, Raimundo Karina, Chou Willis, Collard Harold R
1 Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, California.
2 Interstitial Lung Disease Program, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, Colorado; and.
Am J Respir Crit Care Med. 2017 Sep 15;196(6):756-761. doi: 10.1164/rccm.201701-0091OC.
Respiratory-related hospitalizations of patients with idiopathic pulmonary fibrosis (IPF) are more frequent than those for acute IPF exacerbations and are associated with poor outcomes.
To compare the risk of nonelective hospitalization by type (all-cause, respiratory related, and non-respiratory related) and death after hospitalization with use of pirfenidone versus placebo over 52 weeks using data derived from three phase III IPF clinical trials.
Individual patient data was pooled from three phase III randomized, placebo-controlled studies of pirfenidone for IPF (the two CAPACITY [Clinical Studies Assessing Pirfenidone in IPF: Research of Efficacy and Safety Outcomes] trials and the ASCEND [Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis] trial), including all patients randomized to pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624). The risk of hospitalization over 52 weeks was compared using standard time-to-event methods. Among those hospitalized, the risk of death after hospitalization was compared with adjustment for treatment group propensity.
A total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis. Pirfenidone was associated with lower risk of respiratory-related hospitalization than placebo (7% vs. 12%; hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.77; P = 0.001), but all-cause (HR, 0.91; 95% CI, 0.70-1.19; P = 0.528) or non-respiratory-related hospitalization (HR, 1.32; 95% CI, 0.92-1.88; P = 0.145) was not. Among those hospitalized for any reason, treatment with pirfenidone was associated with lower risk of death after hospitalization up to 52 weeks after randomization, but this association was no longer significant with longer follow-up.
In a pooled analysis of three phase III IPF clinical trials, patients receiving pirfenidone had a lower risk of nonelective respiratory-related hospitalization over the course of 1 year. The effect of pirfenidone on death after hospitalization is uncertain.
特发性肺纤维化（IPF）患者因呼吸相关原因住院的频率高于急性IPF加重患者，且与不良预后相关。
利用三项III期IPF临床试验的数据，比较使用吡非尼酮与安慰剂在52周内按类型（全因、呼吸相关和非呼吸相关）划分的非选择性住院风险以及住院后的死亡风险。
从三项III期吡非尼酮治疗IPF的随机、安慰剂对照研究（两项CAPACITY[评估吡非尼酮在IPF中的疗效和安全性结果的临床研究]试验和ASCEND[评估吡非尼酮在特发性肺纤维化中的疗效和安全性]试验）中汇总个体患者数据，包括所有随机接受2403mg/d吡非尼酮（n = 623）或安慰剂（n = 624）的患者。使用标准的事件发生时间方法比较52周内的住院风险。在住院患者中，比较住院后死亡风险，并对治疗组倾向进行调整。
汇总分析共纳入1247例患者（692例来自CAPACITY试验，555例来自ASCEND试验）。与安慰剂相比，吡非尼酮与呼吸相关住院风险较低相关（7%对12%；风险比[HR]，0.52；95%置信区间[CI]，0.36 - 0.77；P = 0.001），但全因（HR，0.91；95%CI，0.70 - 1.19；P = 0.528）或非呼吸相关住院（HR，1.32；95%CI，0.92 - 1.88；P = 0.145）并非如此。在因任何原因住院的患者中，随机分组后长达52周内，吡非尼酮治疗与住院后死亡风险较低相关，但随着随访时间延长，这种相关性不再显著。
在三项III期IPF临床试验的汇总分析中，接受吡非尼酮治疗的患者在1年内非选择性呼吸相关住院风险较低。吡非尼酮对住院后死亡的影响尚不确定。
