Prescrire Int. 2013 May;22(138):117-9.
Idiopathic pulmonary fibrosis is a rare disorder due to progressive, widespread fibrotic damage of the lung parenchyma. It usually occurs after the age of 50, and its cause is unknown. Symptoms include progressive shortness of breath and nonproductive cough. The course of the disease is marked by exacerbations. Death from respiratory failure occurs about 2 to 5 years after diagnosis. There are currently no drugs that can control or slow the fibrotic process. Pirfenidone, an immunosuppressant, has been authorised in the European Union for the treatment of mild to moderate idiopathic pulmonary fibrosis. Clinical evaluation is based on two double-blind randomised placebo-controlled trials lasting 72 weeks in a total of 779 patients. Mortality, the frequency of exacerbations and the number of lung transplants did not differ significantly between the pirfenidone and placebo groups in either trial. Decline in forced vital capacity was smaller with pirfenidone than with placebo, but the difference was statistically significant in only one of the trials. The small difference in this surrogate endpoint is of questionable clinical relevance. 14.8% of the patients taking pirfenidone 2403 mg/day (maintenance dose according to the marketing authorisation) discontinued treatment because of adverse events, versus 8.6% of patients in the placebo groups. Serious adverse effects included 3 cases of bladder cancer in the pirfenidone groups versus 1 case in the placebo groups. Photosensitivity and skin rash, cardiac arrhythmias and coronary artery disease were more frequent with pirfenidone 2403 mg/day than with placebo. Abnormal transaminase elevation occurred in 4.1% of patients on pirfenidone 2403 mg/day versus 0.6% of patients on placebo. A few cases of acute renal failure were also observed. In practice, there is no evidence that pirfenidone improves quality of life in patients with mild to moderate idiopathic pulmonary fibrosis, or that it slows the progression of pulmonary fibrosis. The adverse effect profile is already burdensome. Pending real therapeutic advance, it is best to avoid pirfenidone altogether and to focus on symptomatic treatment.
特发性肺纤维化是一种罕见的疾病，由于肺实质进行性、广泛性纤维化损伤所致。通常发生在50岁以后，病因不明。症状包括进行性气短和干咳。疾病进程以病情恶化为特征。诊断后约2至5年可因呼吸衰竭死亡。目前尚无药物能够控制或减缓纤维化进程。吡非尼酮，一种免疫抑制剂，已在欧盟获批用于治疗轻至中度特发性肺纤维化。临床评估基于两项双盲随机安慰剂对照试验，共779例患者，试验持续72周。在两项试验中，吡非尼酮组和安慰剂组在死亡率、病情恶化频率和肺移植数量方面均无显著差异。与安慰剂相比，吡非尼酮组用力肺活量的下降幅度较小，但仅在一项试验中差异具有统计学意义。这个替代终点的微小差异在临床相关性方面存疑。服用2403毫克/天吡非尼酮（根据上市许可的维持剂量）的患者中有14.8%因不良事件停药，而安慰剂组为8.6%。严重不良反应包括吡非尼酮组有3例膀胱癌，而安慰剂组有1例。与安慰剂相比，服用2403毫克/天吡非尼酮时，光敏性和皮疹、心律失常及冠状动脉疾病更为常见。服用2403毫克/天吡非尼酮的患者中有4.1%出现转氨酶异常升高，而安慰剂组为0.6%。还观察到少数急性肾衰竭病例。实际上，没有证据表明吡非尼酮能改善轻至中度特发性肺纤维化患者的生活质量，或减缓肺纤维化进程。其不良反应已经很沉重。在真正的治疗取得进展之前，最好完全避免使用吡非尼酮，而专注于对症治疗。
