Ogura Takashi, Azuma Arata, Inoue Yoshikazu, Taniguchi Hiroyuki, Chida Kingo, Bando Masashi, Niimi Yuka, Kakutani Shinichi, Suga Moritaka, Sugiyama Yukihiko, Kudoh Shoji, Nukiwa Toshihiro
Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomioka-higashi, Kanazawa-ku, Yokohama, Kanagawa 236-0051, Japan.
Department of Pulmonary Medicine and Oncology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Respir Investig. 2015 Sep;53(5):232-41. doi: 10.1016/j.resinv.2015.06.001. Epub 2015 Aug 17.
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease with a median survival of 2-5 years and limited treatment options. In 2008, pirfenidone became the first drug to be approved for IPF treatment in Japan. The aim of this study was to assess the safety of pirfenidone for IPF treatment in a clinical setting.
We conducted a safety-oriented post-marketing surveillance of all patients with IPF who were administered pirfenidone in the first year after its launch in Japan. This was a prospective, non-interventional, observational study. Case report forms were used to collect survey data, comprising adverse events, acute exacerbations, patient demographics, concomitant drug use, and concurrent treatment data.
Of the 1371 patients available for safety evaluation, two-thirds had stage III-IV disease. The incidence of total adverse drug reactions (ADRs) was 64.6%. ADRs with an incidence of ≥3% were decreased appetite, photosensitivity reaction, nausea, abdominal discomfort, malaise, somnolence, and hepatic function abnormal. This safety profile was consistent with the findings in phase II and III trials in Japan. The discontinuation rates due to adverse events at 12 months for each disease stage were similar; however, discontinuation caused by disease progression increased with disease severity. Treatment with pirfenidone stabilized both vital capacity and subjective symptoms in most patients (70-80%) treated for at least 6 months.
This post-marketing surveillance in Japan showed that pirfenidone was generally well tolerated in patients with IPF, including those with severe lung function impairment.
特发性肺纤维化（IPF）是一种慢性纤维化性肺病，中位生存期为2至5年，治疗选择有限。2008年，吡非尼酮成为日本首个获批用于治疗IPF的药物。本研究的目的是评估吡非尼酮在临床环境中治疗IPF的安全性。
我们对在日本上市后第一年接受吡非尼酮治疗的所有IPF患者进行了以安全为导向的上市后监测。这是一项前瞻性、非干预性观察性研究。使用病例报告表收集调查数据，包括不良事件、急性加重、患者人口统计学、合并用药以及同时进行的治疗数据。
在1371例可进行安全性评估的患者中，三分之二处于III-IV期疾病。药物不良反应（ADR）的总发生率为64.6%。发生率≥3%的ADR包括食欲减退、光敏反应、恶心、腹部不适、乏力、嗜睡和肝功能异常。这一安全性概况与日本II期和III期试验的结果一致。每个疾病阶段在12个月时因不良事件导致的停药率相似；然而，因疾病进展导致的停药率随疾病严重程度增加。在大多数接受至少6个月治疗的患者（70-80%）中，吡非尼酮治疗使肺活量和主观症状均得到稳定。
日本的这项上市后监测表明，吡非尼酮在IPF患者中总体耐受性良好，包括那些肺功能严重受损的患者。
