Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB, T2N 4Z6, Canada.
Alimentiv Inc (Formerly Robarts Clinical Trials), 100 Dundas St, Suite #200, London, ON, N6A 5B6, Canada.
Dig Dis Sci. 2022 Apr;67(4):1128-1155. doi: 10.1007/s10620-021-06948-w. Epub 2021 Mar 26.
Patients treated with immune checkpoint inhibitors (ICIs) may develop ICI-associated enterocolitis, for which there is no approved treatment.
We aimed to systematically review the efficacy and safety of medical interventions for the prevention and treatment of ICI-associated enterocolitis.
MEDLINE, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials (RCTs), cohort and case-control studies, and case series/reports, evaluating interventions (including corticosteroids, biologics, aminosalicylates, immunosuppressants, and fecal transplantation) for ICI-associated enterocolitis. Clinical, endoscopic, and histologic efficacy endpoints were evaluated. The Grading of Recommendations, Assessment, Development, and Evaluation criteria were used to assess overall quality of evidence.
A total of 160 studies (n = 1514) were included (one RCT, 3 retrospective cohort studies, 156 case reports/case series). Very low quality evidence from one RCT suggests budesonide is not effective for prevention of ICI-associated enterocolitis in ipilimumab-treated patients (relative risk 0.93 [95% confidence interval 0.56, 1.56]). Very low quality evidence suggests that corticosteroids, infliximab, and vedolizumab may be effective for treatment of ICI-associated enterocolitis by inducing clinical response and remission. No validated indices for measuring disease activity were used. Biologic treatment was used in 42% (641/1528) of patients, as reported in 97 studies. ICIs were discontinued in 65% (457/702) of patients, as reported in 63 studies.
Current treatment recommendations for ICI-associated enterocolitis are based on very low quality evidence, primarily from case reports and case series. Large-scale prospective cohort studies and RCTs are needed to develop prophylactic and therapeutic treatments to minimize interruption or discontinuation of oncological therapies.
接受免疫检查点抑制剂（ICI）治疗的患者可能会发生 ICI 相关性肠炎，目前尚无批准的治疗方法。
我们旨在系统地综述预防和治疗 ICI 相关性肠炎的医学干预措施的疗效和安全性。
检索 MEDLINE、EMBASE 和 Cochrane 图书馆，以确定评估干预措施（包括皮质类固醇、生物制剂、氨基水杨酸盐、免疫抑制剂和粪便移植）治疗 ICI 相关性肠炎的随机对照试验（RCT）、队列和病例对照研究以及病例报告/病例系列。评估临床、内镜和组织学疗效终点。使用推荐分级、评估、制定与评价（GRADE）标准评估总体证据质量。
共纳入 160 项研究（n=1514）（1 项 RCT、3 项回顾性队列研究、156 项病例报告/病例系列）。一项 RCT 的极低质量证据表明布地奈德对伊匹单抗治疗患者的 ICI 相关性肠炎预防无效（相对风险 0.93[95%置信区间 0.56，1.56]）。极低质量证据表明，皮质类固醇、英夫利昔单抗和维得利珠单抗可能通过诱导临床缓解来治疗 ICI 相关性肠炎。没有使用验证的疾病活动度评估指标。97 项研究报告有 42%（641/1528）的患者接受生物治疗。63 项研究报告有 65%（457/702）的患者中断 ICI 治疗。
目前针对 ICI 相关性肠炎的治疗建议基于极低质量的证据，主要来自病例报告和病例系列。需要开展大规模前瞻性队列研究和 RCT，以制定预防和治疗措施，尽量减少肿瘤治疗的中断或停止。
