Royal Brompton Hospital, Interstitial Lung Disease Unit, Emmanuel Kaye Building, 1B Manresa Road, London SW3 6LP, UK.
Expert Opin Pharmacother. 2013 Jan;14(1):79-89. doi: 10.1517/14656566.2013.758250.
Novel compounds targeting various aspects of fibrogenesis have been developed consequent to the increasing knowledge of the pathogenetic mechanisms of the interstitial lung diseases (ILDs). The authors review the evolution of treatment approaches in the ILDs, informed by recent placebo-controlled trials, and discuss current clinical trials in which emerging pathogenetic mechanisms are targeted as novel therapeutic agents.
In idiopathic pulmonary fibrosis (IPF), recent randomised, placebo-controlled trials have tested the efficacy of new therapies, and although primary end points have not been met in most, treatment effects have been observed. The demonstration of harmful effects from widely used IPF therapies has been equally important. Pirfenidone and nintedanib are emerging agents that exert pleiotropic effects, reflective of the multiple mechanistic pathways of IPF. Treatment may necessitate a similarly multifaceted approach using combination regimens of antifibrotic and antioxidant agents in order to be effective. In other ILDs, including systemic sclerosis, other connective tissue diseases and pulmonary sarcoidosis, the inflammatory/fibrotic model remains appropriate. Studies in systemic sclerosis have provided 'proof of concept' data for immunosuppressive therapy in the prevention of disease progression but there is a continuing need for controlled clinical trials in the more prevalent ILDs.
In IPF, significant treatment effects have been reported with pirfenidone, nintedanib and N-acetylcysteine. Combinations of these pleiotropic agents, along with future monotherapies, in 'oncological regimens' may hold the key to more effective IPF treatment. In disorders other than IPF, there is an ongoing need for the controlled evaluation of traditional anti-inflammatory and immunosuppressive therapies. 'Cohort enrichment' (the selective recruitment of patients most likely to progress) holds the key to the identification of worthwhile treatment benefits.
随着对间质性肺疾病 (ILDs) 发病机制的不断深入了解，已经开发出针对纤维化各个方面的新型化合物。作者综述了最近安慰剂对照试验指导下的ILDs 治疗方法的进展，并讨论了针对新兴发病机制的新型治疗药物的当前临床试验。
在特发性肺纤维化 (IPF) 中，最近的随机、安慰剂对照试验已经测试了新疗法的疗效，尽管大多数试验的主要终点未达到，但已经观察到治疗效果。广泛使用的 IPF 治疗方法产生有害影响的证明同样重要。吡非尼酮和尼达尼布是具有多效作用的新型药物，反映了 IPF 的多种机制途径。为了有效治疗，可能需要使用联合抗纤维化和抗氧化剂的联合方案采取类似的多方面方法。在其他 ILD 中，包括系统性硬化症、其他结缔组织疾病和肺结节病，炎症/纤维化模型仍然适用。系统性硬化症的研究为预防疾病进展的免疫抑制治疗提供了“概念验证”数据，但在更为普遍的 ILD 中仍需要进行对照临床试验。
在 IPF 中，吡非尼酮、尼达尼布和 N-乙酰半胱氨酸已报告有显著的治疗效果。这些多效性药物的联合用药，以及未来的单一疗法，以“肿瘤学方案”的形式，可能是更有效治疗 IPF 的关键。在除 IPF 以外的疾病中，仍然需要对照评估传统的抗炎和免疫抑制治疗。“队列富集”（选择性招募最有可能进展的患者）是确定有价值的治疗效果的关键。
