Department of Pharmacy, Cleveland Clinic, Cleveland, OH, USA.
Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease & Surgery Institute, Cleveland Clinic, OH, USA.
J Crohns Colitis. 2022 Dec 5;16(12):1924-1932. doi: 10.1093/ecco-jcc/jjac092.
Despite the significant advances in the medical armamentarium for inflammatory bowel diseases [IBD], current treatment options have notable limitations. Durable remission rates remain low, loss of response is common, administration routes are largely parenteral for novel biologics, and medication safety remains a concern. This explains an ongoing unmet need for safe medications with novel mechanisms of action that are administered orally. In line with these criteria, hypoxia-inducible factor [HIF]-1α stabilizers, acting via inhibition of prolyl hydroxylase enzymes, are emerging as an innovative therapeutic strategy. We herein review the mechanism of action and available clinical data for HIF-1α stabilizers and their potential place in the future IBD treatment algorithm.
尽管在炎症性肠病(IBD)的医学武器库方面取得了重大进展,但目前的治疗选择仍存在明显的局限性。持久缓解率仍然较低,应答丧失很常见,新型生物制剂的给药途径主要为注射,药物安全性仍然令人担忧。这就解释了为何人们一直需要安全的新型作用机制药物,这些药物通过口服给药。根据这些标准,缺氧诱导因子(HIF)-1α稳定剂通过抑制脯氨酰羟化酶发挥作用,正在成为一种创新的治疗策略。本文综述了 HIF-1α稳定剂的作用机制和现有临床数据及其在未来 IBD 治疗方案中的潜在地位。