Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada.
Gut. 2023 Jul;72(7):1288-1295. doi: 10.1136/gutjnl-2022-328866. Epub 2023 Jan 30.
To determine whether the use of proton pump inhibitors (PPIs) compared with the use of histamine-2 receptor antagonists (H2RAs) is associated with an increased risk of inflammatory bowel disease (IBD).
Population-based cohort study designed to address the impact of protopathic bias.
General practices contributing data to the UK Clinical Practice Research Datalink GOLD.
1 498 416 initiators of PPIs and 322 474 initiators of H2RAs from 1 January 1990 to 31 December 2018, with follow-up until 31 December 2019. Patients were analysed according to the timing of the IBD diagnosis after treatment initiation (early vs late).
Standardised morbidity ratio weighted Cox proportional hazards models were used to estimate marginal HRs and 95% CIs. In the early-event analysis, IBD diagnoses were assessed within the first 2 years of treatment initiation, an analysis subject to potential protopathic bias. In the late-event analysis, all exposures were lagged by 2 years to account for latency and minimise protopathic bias.
In the early-event analysis, the use of PPIs was associated with an increased risk of IBD within the first 2 years of treatment initiation, compared with H2RAs (HR 1.39, 95% CI 1.14 to 1.69). In contrast, the use of PPIs was not associated with an increased risk of IBD in the late-event analysis (HR 1.05, 95% CI 0.90 to 1.22). The results remained consistent in several sensitivity analyses.
Compared with H2RAs, PPIs were not associated with an increased risk of IBD, after accounting for protopathic bias.
确定质子泵抑制剂（PPIs）与组胺-2 受体拮抗剂（H2RAs）相比，是否会增加炎症性肠病（IBD）的风险。
基于人群的队列研究，旨在解决前病偏向的影响。
向英国临床实践研究数据链接 GOLD 提供数据的普通诊所。
1498416 名 PPI 初始使用者和 322474 名 H2RA 初始使用者，从 1990 年 1 月 1 日至 2018 年 12 月 31 日开始治疗，随访至 2019 年 12 月 31 日。根据治疗开始后 IBD 诊断的时间（早期与晚期）对患者进行分析。
使用标准化发病比加权 Cox 比例风险模型估计边缘 HR 和 95%CI。在早期事件分析中，IBD 诊断在治疗开始后的头 2 年内进行评估，该分析受到前病偏向的影响。在晚期事件分析中，所有暴露都滞后 2 年，以考虑潜伏期并尽量减少前病偏向。
在早期事件分析中，与 H2RAs 相比，PPIs 在治疗开始后的头 2 年内使用与 IBD 风险增加相关（HR 1.39，95%CI 1.14 至 1.69）。相比之下，在晚期事件分析中，PPIs 的使用与 IBD 风险增加无关（HR 1.05，95%CI 0.90 至 1.22）。在几次敏感性分析中，结果仍然一致。
在考虑前病偏向后，与 H2RAs 相比，PPIs 与 IBD 风险增加无关。
