Department of Gastroenterology, Kremlin Bicêtre Hospital, Assistance Publique-Hopitaux de Paris, Le Kremlin Bicêtre;; Paris Sud University, Le Kremlin Bicêtre.
Drug Development Department, Gustave Roussy, Villejuif.
Ann Oncol. 2017 Nov 1;28(11):2860-2865. doi: 10.1093/annonc/mdx403.
Immune check-point blockade agents have shown clinical activity in cancer patients but are associated with immune-related adverse events that could limit their development. The aim of this study was to describe the gastrointestinal immune-related adverse events (GI-irAE) in patients with cancer treated with anti-PD-1.
this is a retrospective study of consecutive adult patients who had a suspected GI-irAE due to anti-PD-1 antibodies between 2013 and 2016. Patients were recruited through a pharmacovigilance registry. Patients' data were reviewed by a multidisciplinary committee that included gastroenterologists, oncologists and a pathologist. Quantitative variables are described by median (range), qualitative variable by frequency (percentage).
Forty-four patients were addressed to a Gastroenterology unit for a suspected GI-IrAE. Twenty patients had a confirmed GI-irAE related to anti-PD-1, which occurred 4.2 months (0.2; 22.1) after the initiation of anti-PD-1. GI-IrAE incidence rate under anti-PD-1 treatment was estimated to be 1.5%. Among patients with GI-IrAE, main symptoms were diarrhoea (n = 16, 80%), abdominal pain (n = 13, 65%), nausea and vomiting (n = 11, 55%), intestinal obstruction (n = 1, 5%), and haematochezia (n = 2, 10%). No patient had colectomy. Four distinct categories of GI-irAE were observed: acute colitis (n = 8, 40%), microscopic colitis (n = 7, 35%), upper gastrointestinal tract inflammation (n = 4, 20%) and pseudo-obstruction (n = 1, 5%). Response rates to corticosteroids were 87.5% (7/8) in acute colitis, 57% (4/7) in microscopic colitis and 75% (3/4) in upper gastrointestinal tract inflammation. Median time to resolution was 36 days (6-172) in acute colitis, and 98 days (42-226) in microscopic colitis.
This study suggests that GI-irAE are different and less frequent with anti PD-1 than with anti CTLA-4.
免疫检查点抑制剂在癌症患者中显示出临床疗效，但与免疫相关的不良反应相关，这可能限制了它们的发展。本研究的目的是描述接受抗 PD-1 治疗的癌症患者的胃肠道免疫相关不良事件（GI-irAE）。
这是一项回顾性研究，纳入了 2013 年至 2016 年间因抗 PD-1 抗体而疑似发生 GI-irAE 的连续成年患者。患者通过药物警戒登记处招募。由包括胃肠病学家、肿瘤学家和病理学家在内的多学科委员会审查患者的数据。定量变量用中位数（范围）描述，定性变量用频率（百分比）描述。
44 例患者因疑似 GI-IrAE 就诊于胃肠病科。20 例患者被确认为与抗 PD-1 相关的 GI-irAE，发生在抗 PD-1 治疗开始后 4.2 个月（0.2；22.1）。抗 PD-1 治疗期间 GI-IrAE 的发生率估计为 1.5%。在发生 GI-IrAE 的患者中，主要症状为腹泻（n=16，80%）、腹痛（n=13，65%）、恶心和呕吐（n=11，55%）、肠梗阻（n=1，5%）和血便（n=2，10%）。无患者行结肠切除术。观察到 4 种不同类别的 GI-irAE：急性结肠炎（n=8，40%）、显微镜结肠炎（n=7，35%）、上胃肠道炎症（n=4，20%）和假性肠梗阻（n=1，5%）。急性结肠炎的皮质类固醇反应率为 87.5%（7/8），显微镜结肠炎为 57%（4/7），上胃肠道炎症为 75%（3/4）。急性结肠炎的中位缓解时间为 36 天（6-172），显微镜结肠炎为 98 天（42-226）。
本研究表明，与抗 CTLA-4 相比，抗 PD-1 引起的 GI-irAE 不同且频率较低。
