Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis.
Importance of endoscopic and histological evaluation in the management of immune checkpoint inhibitor-induced colitis.
复制标题
DOI：
10.1186/s40425-018-0411-1
复制
发表时间：
2018-09-25
影响因子：
10.9
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Abu-Sbeih H;Ali FS;Luo W;Qiao W;Raju GS;Wang Y
免疫检查点抑制剂 (ICPI) 是治疗晚期恶性肿瘤的有效方法，但可能导致免疫介导的腹泻和结肠炎 (IDC)。目前，IDC 的治疗指南仅取决于临床症状。此类不良事件的内窥镜和组织学特征尚未得到充分研究，无法帮助制定治疗计划。我们的目的是描述 IDC 的内镜和组织学特征，并评估它们与临床结果的关联。我们的研究包括因 IDC 接受内窥镜检查的患者（1/2010 至 3/2018）。发病时患有胃肠道感染的患者被排除在外。高风险内镜特征是溃疡深度超过 2 毫米、大于 1 厘米以及广泛的结肠受累。进行单变量和多变量逻辑回归来评估内镜和组织学特征与临床结果的关联。总共纳入182名患者；大多数是白人 (92%)、男性 (65%)，平均年龄为 60 岁。从 ICPI 启动到 IDC 的中位时间为 7 周。 53% 患有 3-4 级腹泻，32% 患有 3-4 级结肠炎。 49 例患者有粘膜溃疡，66 例为非溃疡性炎症，67 例内镜检查正常。溃疡患者钙卫蛋白较高（P = 0.04）。乳铁蛋白检测组织学和内镜炎症的敏感性分别为 90% 和 70%。 IDC 发病后 7 天之前接受内窥镜检查的患者的 IDC 症状持续时间和类固醇治疗持续时间比 IDC 发病 7 天后接受内窥镜检查的患者更短（分别为 P = 0.026 和 P = 0.053）。与接受内镜检查≤30天的患者相比，症状出现时间> 30天的患者接受内镜检查的患者需要更长的类固醇治疗时间（P = 0.02），有更多的症状复发（P <0.01），并且接受英夫利昔单抗/维多珠单抗附加治疗较晚（P = 0.03）。高风险特征与更频繁（P = 0.03）和更长持续时间（P = 0.02）住院以及英夫利昔单抗/维多珠单抗需求相关（P <0.01）。活动性组织学炎症患者的复发率（P<0.01）和重复内镜检查（P<0.01）较多。 47 名患者需要重复内窥镜检查。多变量逻辑回归显示，较长的 ICPI 治疗时间与更频繁的住院治疗相关（OR 1.00；95%CI 1.00–1.01；P<0.01），高危内镜特征与英夫利昔单抗/维多珠单抗的需求相关（OR 3.89；95%CI 1.68-9.01；P<0.01）。高风险内镜特征和活动性组织学炎症是具有临床意义的疾病严重程度的重要标志，应及时使用来设计以 IDC 为重点的治疗算法。本文的在线版本 (10.1186/s40425-018-0411-1) 包含补充材料，可供授权用户使用。
Immune checkpoint inhibitors (ICPI) are efficacious treatments for advanced malignancies but can result in immune mediated diarrhea and colitis (IDC). Currently, the guidelines for the treatment of IDC depend only on clinical symptoms. Endoscopic and histologic features of such adverse events are not well studied in a manner that can help to gauge treatment plans. We aimed to characterize endoscopic and histologic features of IDC and to assess their association with clinical outcomes. Our study included patients who had undergone endoscopy for IDC (1/2010 to 3/2018). Patients with GI infection at time of onset were excluded. High-risk endoscopic features were ulcers deeper than 2 mm, larger than 1 cm, and extensive colonic involvement. Univariate and multivariate logistic regression were performed to assess the association of endoscopic and histological features with clinical outcomes. A total of 182 patients was included; most were white (92%), males (65%) with a mean age of 60 years. Median time from ICPI initiation to IDC was 7 weeks. Fifty-three percent had grade 3–4 diarrhea, and 32% grade 3–4 colitis. Forty-nine patients had mucosal ulcerations, 66 non-ulcerative inflammation and 67 normal endoscopy. Calprotectin was higher in patients with ulceration (P = 0.04). The sensitivity of lactoferrin to detect histologic and endoscopic inflammation was 90% and 70% respectively. Patients who underwent endoscopy earlier than 7 days after IDC onset had shorter duration of IDC symptoms and duration of steroid treatment than those who underwent endoscopy after 7 days of IDC onset (P = 0.026 and P = 0.053, respectively). Patients who underwent endoscopy > 30 days of symptom onset required longer duration of steroids (P = 0.02), had more recurrent symptoms (P < 0.01) and received later infliximab/vedolizumab add-on therapy than did those who underwent endoscopy ≤30 days (P = 0.03). High-risk features were associated with more frequent (P = 0.03) and longer duration (P = 0.02) hospitalization and infliximab/vedolizumab requirement (P < 0.01). Patients with active histological inflammation had more recurrence (P < 0.01) and repeat endoscopy (P < 0.01). Repeat endoscopy was required in 47 patients. A multivariate logistic regression revealed that longer ICPI treatment was associated with more frequent hospitalizations (OR 1.00; 95%CI 1.00–1.01; P < 0.01) and high-risk endoscopic features were associated with the requirement of infliximab/vedolizumab (OR 3.89; 95%CI 1.68–9.01; P < 0.01). High risk endoscopic features and active histologic inflammation represent important markers of disease severity with clinical implications and should be used in a timely manner to devise IDC-focused treatment algorithms. The online version of this article (10.1186/s40425-018-0411-1) contains supplementary material, which is available to authorized users.
登录
查看更多内容
DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
7.3
作者：
Dougan M
通讯作者：
Dougan M
DOI：
10.1056/nejmoa1709684
发表时间：
2017-10-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Wolchok JD;Chiarion-Sileni V;Gonzalez R;Rutkowski P;Grob JJ;Cowey CL;Lao CD;Wagstaff J;Schadendorf D;Ferrucci PF;Smylie M;Dummer R;Hill A;Hogg D;Haanen J;Carlino MS;Bechter O;Maio M;Marquez-Rodas I;Guidoboni M;McArthur G;Lebbé C;Ascierto PA;Long GV;Cebon J;Sosman J;Postow MA;Callahan MK;Walker D;Rollin L;Bhore R;Hodi FS;Larkin J
通讯作者：
Larkin J
影响因子：
45.3
作者：
Horn, Leora;Spigel, David R.;Eberhardt, Wilfried E. E.
通讯作者：
Eberhardt, Wilfried E. E.
影响因子：
12.6
作者：
Verschuren, Eduard Cornelis;van den Eertwegh, Alfonsus Johannes;de Boer, Nanne Klaas
通讯作者：
de Boer, Nanne Klaas