Bhushan Sheena, Kowdley Kris V
Liver Institute Northwest, Seattle.
Elson S. Floyd College of Medicine, Washington State University, Seattle, Washington, USA.
Curr Opin Gastroenterol. 2025 Jul 1;41(4):281-288. doi: 10.1097/MOG.0000000000001109. Epub 2025 Jun 5.
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are rare, chronic cholestatic diseases associated with significant morbidity. While previously approved therapies for PBC, including ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) have substantially altered the natural course of the disease and improved patient survival, they have several limitations including an incomplete therapeutic response, patient intolerance and a lack of symptom relief.
Peroxisome proliferator-activated receptor (PPAR) agonists have emerged as promising therapeutic agents capable of achieving biochemical remission and alleviating debilitating symptoms such as pruritus. Elafibranor and Seladelpar were recently granted accelerated approval by the FDA as second-line treatment option for PBC. Although no treatment has yet received approval for PSC, several PPAR agonists have been evaluated in clinical trials.
This review highlights the evolving role of PPAR agonists as second-line agents for PBC and investigational treatments for PSC.
原发性胆汁性胆管炎（PBC）和原发性硬化性胆管炎（PSC）是罕见的慢性胆汁淤积性疾病，伴有明显的发病率。虽然先前批准用于PBC的疗法，包括熊去氧胆酸（UDCA）和奥贝胆酸（OCA）已大幅改变疾病的自然进程并改善了患者生存率，但它们有几个局限性，包括治疗反应不完全、患者不耐受和缺乏症状缓解。
过氧化物酶体增殖物激活受体（PPAR）激动剂已成为有前景的治疗药物，能够实现生化缓解并减轻诸如瘙痒等使人衰弱的症状。艾拉非布诺和塞拉德尔帕最近获得美国食品药品监督管理局（FDA）加速批准，作为PBC的二线治疗选择。虽然尚无治疗方法获批用于PSC，但几种PPAR激动剂已在临床试验中进行了评估。
本综述强调了PPAR激动剂作为PBC二线药物和PSC研究性治疗方法不断演变的作用。
