Dart Robin J, Irving Peter M
a IBD Centre, Department of Gastroenterology , St Thomas' Hospital , London , UK.
b Immunosurveillance Lab , Francis Crick Institute , London , UK.
Expert Rev Clin Immunol. 2017 Sep;13(9):877-888. doi: 10.1080/1744666X.2017.1351298. Epub 2017 Jul 12.
Thiopurines are central to inflammatory bowel disease (IBD) therapeutics, either as monotherapy or in combination with newer biologic therapies, however it is only recently that focus has increased on improving effectiveness and tolerability through optimisation. Areas covered: We review the role of thiopurines in IBD and the importance of the timing of initiation of therapy. Drug metabolism and pharmacogenetics have increasingly played a role in determining dosing and dose optimisation and we review the rationale for this in both thiopurine monotherapy and in combination with biologic agents. We also discuss allopurinol co-therapy as a strategy for enhancing both efficacy and tolerability of thiopurine therapy. Although immunomodulators carry safety considerations, we discuss methods of optimisation to minimise side-effects and maximise safety to ensure the broadest number of patients can benefit. Expert commentary: We provide a practical guide to drug initiation and dose optimisation in a clinical setting, and address potential treatment duration. The forward view considers the place for thiopurines in the treatment of IBD, and how the application of the plethora of genetic data may help inform thopurine therapy in the future.
硫嘌呤类药物在炎症性肠病（IBD）治疗中至关重要，无论是作为单一疗法还是与新型生物疗法联合使用。然而，直到最近，通过优化来提高疗效和耐受性才越来越受到关注。涵盖领域：我们回顾硫嘌呤类药物在IBD中的作用以及治疗起始时机的重要性。药物代谢和药物遗传学在确定剂量和剂量优化方面发挥着越来越重要的作用，我们回顾了在硫嘌呤单一疗法以及与生物制剂联合使用时这样做的基本原理。我们还讨论了使用别嘌醇联合治疗作为提高硫嘌呤治疗疗效和耐受性的一种策略。尽管免疫调节剂存在安全性方面的考量，但我们讨论了优化方法以尽量减少副作用并最大化安全性，确保尽可能多的患者能够受益。专家评论：我们提供了在临床环境中药物起始和剂量优化的实用指南，并探讨了潜在的治疗持续时间。前瞻性展望考虑了硫嘌呤类药物在IBD治疗中的地位，以及大量遗传数据的应用在未来如何有助于指导硫嘌呤治疗。
