Medical University Clinic, Canton Hospital Baselland, Liestal, Switzerland; University of Basel, Liestal, Switzerland.
National Institute for Health Research Biological Research Unit, Royal Brompton Hospital, London, United Kingdom; National Heart and Lung Institute, Imperial College, London, United Kingdom.
Pharmacol Ther. 2015 Aug;152:18-27. doi: 10.1016/j.pharmthera.2015.04.005. Epub 2015 May 3.
Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the idiopathic interstitial pneumonias with an estimated 5-year survival of approximately 20%. In the last two decades our understanding of disease pathogenesis has substantially evolved and novel compounds have been developed consequent to the increasing knowledge of the mechanisms underlying disease pathobiology. The disease appears to be driven - following chronic injury - by abnormal/dysfunctional alveolar epithelial cells that promote fibroblast recruitment and proliferation, resulting in scarring of the lung and irreversible loss of function. With very few exceptions, clinical trials evaluating novel potential therapies have provided disappointing results. More recently, pirfenidone and nintedanib, two compounds with pleiotropic mechanisms of action, have proven effective in slowing functional decline and disease progression in IPF patients with mild to moderate functional impairment, highlighting the importance of timely diagnosis and administration of treatment in early stages of disease. However, due to the complexity and uncertainties intrinsic to IPF, it is essential that each therapeutic strategy be tailored to the individual patient, after evaluation of potential benefits and risks. This article provides an overview of the most recent clinical trials in IPF and discusses how their results are going to change the clinical and clinical research landscape in IPF. A number of agents with high potential are currently being tested and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF.
特发性肺纤维化（IPF）是特发性间质性肺炎中最常见和最致命的一种，估计 5 年生存率约为 20%。在过去的二十年中，我们对疾病发病机制的理解有了实质性的发展，并且由于对疾病病理生物学机制的认识不断增加，新型化合物也得到了开发。在慢性损伤后，疾病似乎由异常/功能失调的肺泡上皮细胞驱动，这些细胞促进成纤维细胞的募集和增殖，导致肺瘢痕形成和不可逆转的功能丧失。除了极少数例外，评估新型潜在疗法的临床试验结果令人失望。最近，吡非尼酮和尼达尼布这两种具有多种作用机制的化合物，已被证明能有效减缓有轻度至中度功能障碍的 IPF 患者的功能下降和疾病进展，这突出表明在疾病早期及时诊断和治疗的重要性。然而，由于 IPF 固有的复杂性和不确定性，在评估潜在益处和风险后，为每个患者量身定制治疗策略至关重要。本文概述了 IPF 的最新临床试验，并讨论了它们的结果将如何改变 IPF 的临床和临床研究格局。目前正在测试许多具有高潜力的药物，还有许多药物已准备好进行临床试验。完成这些试验对于实现治愈 IPF 患者的最终目标至关重要。
