Kapur Saurabh, Hanauer Stephen B
Kansas University Medical Center, Kansas, KS, USA.
Northwestern University, Chicago, IL, USA.
Curr Treat Options Gastroenterol. 2019 Dec;17(4):435-448. doi: 10.1007/s11938-019-00249-y.
With the advent of biologic therapies for the treatment of IBD, the roles of thiopurines have continued to evolve. This review will focus on recent advances in pharmacology and the safety and efficacy of thiopurines as maintenance therapies for steroid-induced remissions, post-surgical maintenance of remission, and as combination therapies to reduce immunogenicities of biologic agents.
Due to pharmacogenetics of TPMT, thiopurine dosing is more effectively based on monitoring of thiopurine metabolites rather than weight-based dosing. Thiopurines continue to have a role as maintenance therapy after steroid-induced remissions and in combination with biologics to induce and maintain remission. Safety monitoring includes measurements of blood counts, liver chemistries, as well as dermatologic evaluations and protection from sun exposure. Thiopurines appear to be safe during pregnancies and while very uncommon, lymphomas (including hepatosplenic T cell lymphomas) remain a recognized risk, particularly in younger and older males.
随着用于治疗炎症性肠病的生物疗法的出现,硫唑嘌呤的作用持续演变。本综述将聚焦于硫唑嘌呤药理学的最新进展,以及其作为类固醇诱导缓解后的维持疗法、术后缓解维持疗法,和作为降低生物制剂免疫原性的联合疗法的安全性及疗效。
由于硫嘌呤甲基转移酶(TPMT)的药物遗传学,硫唑嘌呤的给药基于硫嘌呤代谢物监测比基于体重给药更有效。硫唑嘌呤在类固醇诱导缓解后作为维持疗法以及与生物制剂联合使用以诱导和维持缓解方面仍发挥作用。安全性监测包括血细胞计数、肝功能检查,以及皮肤评估和防晒。硫唑嘌呤在孕期似乎是安全的,虽然非常罕见,但淋巴瘤(包括肝脾T细胞淋巴瘤)仍然是一种公认的风险,特别是在年轻和老年男性中。