吡非尼酮治疗特发性肺纤维化患者安全性的开放标签II期研究（PIPF-002）
An Open-Label, Phase II Study of the Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (PIPF-002).
作者信息
Gotfried Mark H, Girod Carlos E, Antin-Ozerkis Danielle, Burgess Tracy, Strombom Indiana, Stauffer John L, Kirchgaessler Klaus-Uwe, Padilla Maria L
机构信息
Pulmonary Associates, Phoenix, AZ, USA.
The University of Texas Southwestern Medical Center, Dallas, TX, USA.
出版信息
Pulm Ther. 2018 Jun;4(1):59-71. doi: 10.1007/s41030-018-0053-y. Epub 2018 Apr 5.
INTRODUCTION
PIPF-002 was a phase 2, multicenter, open-label study of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) or other types of pulmonary fibrosis (PF). PIPF-002 terminated after pirfenidone became commercially available in the United States. The goal of PIPF-002 was to characterize the long-term safety of pirfenidone in these patients.
METHODS
Between August 2003 and September 2006, 83 patients (IPF: 81, PF: 2) enrolled. Patients received pirfenidone in three divided doses daily, with the maintenance dose and schedule determined by enrollment group assignment. Treatment continued until patient withdrawal or study termination (2015). Treatment-emergent adverse events (TEAEs) were assessed by descriptive statistics.
RESULTS
At baseline, median age was 70 years, mean percent predicted forced vital capacity was 67.7%, 33.7% of patients had cardiac disorders, 51.8% had gastroesophageal reflux disease, and 63.9% were receiving concomitant prednisone. Median pirfenidone dose and exposure duration were 2400 mg/day and 3.0 years, respectively. Cumulative total exposure was 279.7 patient-exposure years (PEY). Most patients (98.8%) reported ≥ 1 TEAE, with an overall incidence rate of 460.5 per 100 PEY. The most frequent TEAEs (incidence rate per 100 PEY) were nausea (23.6), IPF progression (16.1), fatigue (11.8), dyspnea (11.4), upper respiratory tract infection (11.4), and cough (10.7). Serious TEAEs were reported in 49 patients; the most frequent serious TEAEs were IPF progression and pneumonia. The most common reason for discontinuation was TEAEs (35 patients; 12.5 patients per 100 PEY), most frequently IPF progression and nausea. Overall, 21 patients died (7.5 per 100 PEY); 16 deaths were IPF-related.
CONCLUSIONS
Long-term safety and tolerability of pirfenidone findings in this study were consistent with the known safety profile of pirfenidone; no new safety signals were identified. These data support the continued use of pirfenidone in patients with IPF.
FUNDING
F. Hoffmann-La Roche Ltd./Genentech, Inc.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT00080223. Plain language summary available for this article.
引言
PIPF - 002是一项关于吡非尼酮治疗特发性肺纤维化（IPF）或其他类型肺纤维化（PF）患者的2期多中心开放标签研究。在美国吡非尼酮上市后，PIPF - 002研究终止。PIPF - 002的目标是明确吡非尼酮在这些患者中的长期安全性。
方法
2003年8月至2006年9月，83例患者入组（IPF：81例，PF：2例）。患者每日分三次服用吡非尼酮，维持剂量和服药方案根据入组分组确定。治疗持续至患者退出或研究终止（2015年）。通过描述性统计评估治疗期间出现的不良事件（TEAE）。
结果
基线时，中位年龄为70岁，预计用力肺活量平均百分比为67.7%，33.7%的患者患有心脏疾病，51.8%患有胃食管反流病，63.9%的患者同时接受泼尼松治疗。吡非尼酮的中位剂量和暴露持续时间分别为2400毫克/天和3.0年。累积总暴露量为279.7患者 - 暴露年（PEY）。大多数患者（98.8%）报告了≥1次TEAE，总发生率为每100 PEY 460.5次。最常见的TEAE（每100 PEY发生率）为恶心（23.6）、IPF进展（16.1）、疲劳（11.8）、呼吸困难（11.4）、上呼吸道感染（11.4）和咳嗽（10.7）。49例患者报告了严重TEAE；最常见的严重TEAE为IPF进展和肺炎。停药的最常见原因是TEAE（35例患者；每100 PEY 12.5例患者），最常见的是IPF进展和恶心。总体而言，21例患者死亡（每100 PEY 7.5例）；16例死亡与IPF相关。
结论
本研究中吡非尼酮的长期安全性和耐受性结果与已知的吡非尼酮安全性特征一致；未发现新的安全信号。这些数据支持吡非尼酮在IPF患者中继续使用。
资助
F. Hoffmann - La Roche Ltd./Genentech, Inc.
试验注册
ClinicalTrials.gov标识符，NCT00080223。本文提供通俗易懂的摘要。
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