质子泵抑制剂的长期使用与肾细胞癌患者免疫检查点抑制剂相关性结肠炎风险增加相关。
Chronic Use of Proton Pump Inhibitors Is Associated With an Increased Risk of Immune Checkpoint Inhibitor Colitis in Renal Cell Carcinoma.
机构信息
Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
出版信息
Clin Genitourin Cancer. 2022 Jun;20(3):260-269. doi: 10.1016/j.clgc.2022.01.017. Epub 2022 Feb 1.
INTRODUCTION
Immune checkpoint inhibitors (ICIs) have become a standard of care in metastatic renal cell carcinoma (mRCC) but are associated with immune-related adverse events (irAEs) including colitis. Growing evidence suggests proton pump inhibitors (PPIs) increase the risk of inflammatory bowel disease (IBD). Given the pathophysiological overlap between IBD and ICI colitis, we sought to evaluate the relationship between PPI use and ICI colitis in mRCC patients.
PATIENTS AND METHODS
We performed a retrospective study of adult patients who received ICI therapy for mRCC between 2015 and 2018 at University of Texas Southwestern Medical Center affiliated hospitals. Clinical characteristics, oncological outcomes, ICI colitis details, and PPI use details were collected by manual chart review. The diagnosis of ICI colitis was made via biopsy when available, or by clinical criteria (symptoms and response to immunosuppressive therapy) when biopsy specimens were unavailable or inconclusive. Univariable and multivariable logistic regression analyses were conducted to assess the potential contribution of PPIs to ICI colitis.
RESULTS
A total of 176 patients received ICI therapy for mRCC, of which 16 (9.1%) were diagnosed with ICI colitis. Patients with ICI colitis presented with elevated stool lactoferritin and calprotectin and a wide range of endoscopic and histologic findings. There were no significant differences between patients with and without ICI colitis in age, gender, medical comorbidities, RCC history, and overall survival. However, exposure to ipilimumab and PPI use were more frequently observed in patients with ICI colitis than those without. In univariable and multivariable logistic regression analyses, exposure to ipilimumab and chronic use of PPIs > 8 weeks were significantly associated with ICI colitis.
CONCLUSION
In addition to ipilimumab use, chronic use of PPIs may be associated with ICI colitis in patients with mRCC.
简介
免疫检查点抑制剂（ICIs）已成为转移性肾细胞癌（mRCC）的标准治疗方法，但与包括结肠炎在内的免疫相关不良反应（irAEs）相关。越来越多的证据表明质子泵抑制剂（PPIs）会增加炎症性肠病（IBD）的风险。鉴于 IBD 和 ICI 结肠炎之间存在病理生理学重叠，我们试图评估 PPI 使用与 mRCC 患者 ICI 结肠炎之间的关系。
患者和方法
我们对 2015 年至 2018 年期间在德克萨斯大学西南医学中心附属医院接受 ICI 治疗的 mRCC 成年患者进行了回顾性研究。通过手动图表审查收集临床特征、肿瘤学结果、ICI 结肠炎详细信息和 PPI 使用详细信息。ICI 结肠炎的诊断通过活检获得，如果活检标本不可用或不确定，则通过临床标准（症状和对免疫抑制治疗的反应）进行诊断。进行单变量和多变量逻辑回归分析，以评估 PPI 对 ICI 结肠炎的潜在贡献。
结果
共有 176 名患者接受了 ICI 治疗 mRCC，其中 16 名（9.1%）被诊断为 ICI 结肠炎。患有 ICI 结肠炎的患者表现出粪便乳铁蛋白和钙卫蛋白升高，以及广泛的内镜和组织学发现。患有 ICI 结肠炎的患者与无 ICI 结肠炎的患者在年龄、性别、合并症、RCC 病史和总生存期方面无显著差异。然而，与无 ICI 结肠炎的患者相比，接受伊匹单抗和 PPI 暴露的患者更为常见。在单变量和多变量逻辑回归分析中，接受伊匹单抗和慢性使用 PPI > 8 周与 ICI 结肠炎显著相关。
结论
除了使用伊匹单抗外，慢性使用 PPI 可能与 mRCC 患者的 ICI 结肠炎有关。
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