背景:免疫检查点抑制剂(ICIs)包括抗CTLA-4,抗PD-1和抗PD-L1抗体已越来越多地用于各种恶性肿瘤。这些ICI激活免疫功能来治疗恶性肿瘤;然而,这导致了称为免疫相关不良事件(irAE)的特征性并发症.在胃肠道,ICI会导致腹泻和小肠结肠炎等不良事件,因此保证停止治疗。这些irAE需要抑制免疫力的治疗;然而,没有基于已批准指南的治疗策略的报道.本综述旨在根据ICI诱导的难治性结肠炎的诊断,探讨其治疗现状。治疗,和预后。
结论:我们根据系统评价和荟萃分析(PRISMA)清单的首选报告项目对研究进行了系统评价。两名调查人员于2019年1月搜索了PubMed和Scopus。我们提取数据,包括ICI治疗的结肠炎和腹泻患者的数量。根据美国国家癌症研究所的不良事件通用术语标准(CTCAE)定义和皮质类固醇治疗和抗TNF-α抗体治疗的病例的进展(例如,英夫利昔单抗)进行记录。对于用抗TNF-α-抗体没有改善的病例,还记录了进一步治疗的细节。在接受抗CTLA-4抗体的患者中,14.6%的患者使用皮质类固醇,对5.7%的患者给予英夫利昔单抗。在接受抗PD-1/PD-L1抗体的患者中,2.37%的患者接受了糖皮质激素治疗.对于英夫利昔单抗治疗失败的难治性病例,每2周继续使用英夫利昔单抗,他克莫司管理,长期的皮质类固醇治疗,结肠切除术,或维多珠单抗给药报告.
结论:治疗ICI诱导的结肠炎对于避免停止癌症治疗是重要的。据报道,许多用于炎性肠病的治疗剂可有效治疗难治性ICI诱导的结肠炎。
BACKGROUND: Immune checkpoint inhibitors (ICIs) including anti-CTLA-4, anti-PD-1, and anti-PD-L1 antibodies have been increasingly used for various malignancies. These ICIs activate immune functions to treat malignant tumors; however, this causes characteristic complications called immune-related adverse events (irAE). In the gastrointestinal tract, ICIs cause adverse events such as diarrhea and enterocolitis, thus warranting treatment discontinuation. These irAEs require treatment that suppresses immunity; however, no treatment strategies based on approved guidelines have been reported. This review aimed to investigate the current treatment status for refractory cases of ICI-induced colitis in accordance with their diagnosis, therapy, and prognosis.
CONCLUSIONS: We systematically reviewed studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist. Two investigators searched PubMed and Scopus in January 2019. We extracted data, including the number of ICI-treated patients developing colitis and diarrhea. The number of cases classified as severe per the National Cancer Institute\'s Common Terminology Criteria for Adverse Events (CTCAE) definitions and the progress of corticosteroid-treated and anti-TNF-α- antibody-treated cases (e.g., infliximab) were recorded. Details of further treatment were also recorded for cases that did not improve with antiTNF-α- antibody. Among patients receiving anti-CTLA-4 antibody, corticosteroids were administered to 14.6% of patients, and infliximab was administered to 5.7% of patients. Among patients receiving anti-PD-1/PD-L1 antibody, corticosteroids were administered to 2.37% of patients. For refractory cases unsuccessful with infliximab, the continuation of infliximab every 2 weeks, tacrolimus administration, prolonged corticosteroid treatment, colectomy, or vedolizumab administration were reported.
CONCLUSIONS: Treatment of ICI-induced colitis is important to avoid the need to discontinue cancer treatment. Many therapeutic agents for inflammatory bowel disease are reportedly effective in treating refractory ICI-induced colitis.