Université Paris-Sud, Hôpital Bicêtre, INSERM UMR_S999, Le Kremlin-Bicêtre, France.
George Washington University, Dept of Medicine, Washington, DC, USA.
Eur Respir J. 2019 Jan 24;53(1). doi: 10.1183/13993003.01908-2018. Print 2019 Jan.
Until 20 years ago the treatment of pulmonary arterial hypertension (PAH) was based on case reports and small series, and was largely ineffectual. As a deeper understanding of the pathogenesis and pathophysiology of PAH evolved over the subsequent two decades, coupled with epidemiological studies defining the clinical and demographic characteristics of the condition, a renewed interest in treatment development emerged through collaborations between international experts, industry and regulatory agencies. These efforts led to the performance of robust, high-quality clinical trials of novel therapies that targeted putative pathogenic pathways, leading to the approval of more than 10 novel therapies that have beneficially impacted both the quality and duration of life. However, our understanding of PAH remains incomplete and there is no cure. Accordingly, efforts are now focused on identifying novel pathogenic pathways that may be targeted, and applying more rigorous clinical trial designs to better define the efficacy of these new potential treatments and their role in the management scheme. This article, prepared by a Task Force comprised of expert clinicians, trialists and regulators, summarises the current state of the art, and provides insight into the opportunities and challenges for identifying and assessing the efficacy and safety of new treatments for this challenging condition.
直到 20 年前，肺动脉高压 (PAH) 的治疗还基于病例报告和小系列研究，且效果不佳。随着对 PAH 的发病机制和病理生理学的深入了解在随后的二十年中不断发展，再加上对该疾病的临床和人口统计学特征进行的流行病学研究，通过国际专家、行业和监管机构之间的合作，对治疗开发产生了新的兴趣。这些努力导致了针对潜在致病途径的新型治疗方法的稳健、高质量临床试验的开展，批准了 10 多种新型疗法，这些疗法都显著改善了患者的生活质量和延长了患者的生存时间。然而，我们对 PAH 的认识仍然不完整，尚无治愈方法。因此，目前的工作重点是确定可能成为治疗靶点的新的致病途径，并应用更严格的临床试验设计来更好地定义这些新的潜在治疗方法的疗效及其在治疗方案中的作用。本文由专家临床医生、试验研究者和监管机构组成的工作组编写，总结了目前的最新进展，并深入探讨了确定和评估针对这一具有挑战性疾病的新治疗方法的疗效和安全性的机遇和挑战。
