Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.
Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.
Expert Opin Pharmacother. 2024 Sep;25(13):1835-1849. doi: 10.1080/14656566.2024.2407022. Epub 2024 Oct 11.
Primary sclerosing cholangitis (PSC) is the most specific hepatobiliary extraintestinal manifestation in inflammatory bowel disease (IBD). PSC ultimately has a poor prognosis, with disease progression resulting in liver cirrhosis and subsequent liver failure. While there is current data for the medical management of IBD, the optimal approach for concurrent PSC-IBD is unclear.
This review focuses on the current literature of pharmacotherapy in the PSC-IBD population including anti-tumor necrosis factor agents, vedolizumab, JAK inhibitors, IL-12/23 inhibitors, and thiopurines. Regarding PSC-IBD, it focuses on effectiveness of IBD therapies on liver biochemistry and IBD activity as well as the advent of clinically relevant liver outcomes and safety. The authors also address the need for further advances in research.
The longer-term data for pharmacological management for IBD is well established. In the concomitant PSC-IBD population there is no drug to date that has effectively reduced disease related morbidity and mortality outcomes. There are limitations in the current, mostly retrospective data on IBD drugs in PSC-IBD with respect to samples sizes, heterogenous outcomes, and lack of a high-quality surrogate endpoint in PSC. However, current data for adalimumab offers encouraging results which require further exploration with larger prospective studies.
原发性硬化性胆管炎(PSC)是炎症性肠病(IBD)最特异的肝胆肠外表现。PSC 最终预后较差,疾病进展可导致肝硬化和随后的肝功能衰竭。虽然目前有 IBD 的药物治疗数据,但并发 PSC-IBD 的最佳治疗方法尚不清楚。
这篇综述重点介绍了 PSC-IBD 人群中药物治疗的当前文献,包括抗肿瘤坏死因子制剂、vedolizumab、JAK 抑制剂、IL-12/23 抑制剂和硫唑嘌呤。关于 PSC-IBD,重点关注 IBD 治疗对肝脏生化和 IBD 活动的有效性,以及临床相关的肝脏结局和安全性的出现。作者还讨论了进一步研究的必要性。
IBD 药物治疗的长期数据已经得到充分确立。在并发 PSC-IBD 的人群中,迄今为止,尚无药物能有效降低与疾病相关的发病率和死亡率。在 PSC-IBD 中,IBD 药物的当前数据主要是回顾性的,存在样本量、异质性结局和 PSC 中缺乏高质量替代终点的局限性。然而,阿达木单抗的现有数据提供了令人鼓舞的结果,需要进一步通过更大的前瞻性研究进行探索。