Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Gut. 2021 Apr;70(4):677-686. doi: 10.1136/gutjnl-2019-320185. Epub 2020 Oct 1.
Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn's disease (CD), including their impact on need for surgery.
Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines.
Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015).
Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD.
硫嘌呤类药物被广泛用于炎症性肠病（IBD）的维持治疗，但它们的应用证据有限，其作用也越来越受到质疑。本研究使用迄今为止报告的最大系列，评估了硫嘌呤类药物在溃疡性结肠炎（UC）和克罗恩病（CD）中的长期疗效，包括它们对手术需求的影响。
该研究在英国 IBD 生物资源库中纳入了 11928 名患者（4968 名 UC，6960 名 CD），这些患者最初接受硫嘌呤单药治疗，目的是维持药物诱导的缓解。使用患者水平的数据和一个定义来回顾性评估疗效，该定义要求在使用硫嘌呤类药物时避免升级为生物治疗或手术。分析包括总体疗效、治疗升级的时间事件分析以及比较硫嘌呤类药物耐受和不耐受患者的手术率。
使用 68132 患者年的暴露数据，硫嘌呤单药治疗在 4968 名 UC 患者中的 2617 名（52.7%）和 6960 名 CD 患者中的 2378 名（34.2%）中，在治疗期间表现出有效性（p<0.0001）。多变量分析证实了这一差异：在调整了治疗时代等变量后，硫嘌呤单药治疗在 CD 中的疗效明显低于 UC（OR 0.47，95%CI 0.43 至 0.51，p<0.0001）。硫嘌呤不耐受与 UC 患者手术风险增加相关（HR 2.44，p<0.0001）；而对 CD 患者手术需求的影响较小（HR=1.23，p=0.0015）。
硫嘌呤单药治疗是 UC 的一种有效长期治疗方法，但在 CD 中的疗效明显降低。
