Worse Survival and Gastrointestinal Toxicity Outcomes Among Patients Receiving Proton Pump Inhibitors During Checkpoint Inhibitor Therapy.

Malek Shatila, Samanthika Devalaraju, Kei Takigawa, Christine Catinis, Irene Lee, Elliot Baerman, Sean Ngo, Nitish Mittal, Stephen Glombicki, Antonio Pizuorno Machado, Linfeng Lu, Abdullah Sagar Aleem, John Thompson, Pauline Funchain, Shilpa Grover, Hao Chi Zhang, Anusha Shirwaiker Thomas, Yinghong Wang
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Abstract

Background: Immune checkpoint inhibitors (ICIs) for cancer carry a risk of immune-related adverse events (irAEs). Upper and lower gastrointestinal tract inflammation are common toxicities. Proton pump inhibitors (PPIs) are used to treat upper gastrointestinal irAEs. Studies have suggested these agents may also worsen lower gastrointestinal irAEs. Our study evaluated the effect of PPI exposure on gastrointestinal irAE severity.

Methods: This was a single-center retrospective chart review including all patients receiving ICIs between January 2010 and February 2024 who developed upper or lower gastrointestinal toxicity. Patients were grouped based on PPI use, defined as receiving a PPI any time from 3 months before ICI initiation until gastrointestinal toxicity diagnosis.

Results: A total of 1,228 patients were included: 88 (7.2%) with upper gastrointestinal toxicity and 1,140 (92.8%) with lower toxicity. Upper gastrointestinal irAEs were more severe among PPI users (69.6% with grade 3 toxicity in the PPI group vs 29.6% in the non-PPI group; P<.05). Similarly, lower gastrointestinal irAEs were more severe among PPI users, with a higher need for multiple lines of biologic treatment, higher hospitalization rates, and longer hospital stays (P<.05 for all). PPI use was associated with significantly worse overall survival among patients receiving ICIs (P<.05).

Conclusions: Our study is the largest to date showing the impact of PPI use on immunotherapy toxicity. PPI use may predispose to more severe toxicities and worse outcomes. PPIs may also reduce immunotherapy efficacy, as reflected by worse overall survival. These findings support the judicious use of PPIs in patients receiving ICIs and call for prospective studies to validate our results.

在检查点抑制剂治疗期间接受质子泵抑制剂治疗的患者更差的生存和胃肠道毒性结果。
背景:用于癌症的免疫检查点抑制剂(ICIs)具有免疫相关不良事件(irAEs)的风险。上、下胃肠道炎症是常见的毒性反应。质子泵抑制剂(PPIs)用于治疗上胃肠道irAEs。研究表明,这些药物也可能使下消化道irae恶化。我们的研究评估了PPI暴露对胃肠道irAE严重程度的影响。方法:这是一项单中心回顾性图表综述,包括2010年1月至2024年2月期间接受ICIs治疗的所有出现上消化道或下消化道毒性的患者。患者根据使用PPI进行分组,定义为在ICI开始前3个月至胃肠道毒性诊断期间接受PPI治疗。结果:共纳入1228例患者:上消化道毒性88例(7.2%),低毒性1140例(92.8%)。上消化道irae在PPI使用者中更为严重(PPI组为69.6%,为3级毒性,非PPI组为29.6%;结论:我们的研究是迄今为止最大的显示PPI使用对免疫治疗毒性影响的研究。PPI的使用可能导致更严重的毒性和更糟糕的结果。PPIs也可能降低免疫治疗的疗效,这反映在更差的总生存率上。这些发现支持在接受ici的患者中明智地使用PPIs,并呼吁进行前瞻性研究来验证我们的结果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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