Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Division of Gastroenterology, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Inflamm Bowel Dis. 2024 Sep 3;30(9):1443-1453. doi: 10.1093/ibd/izad196.
Very early onset inflammatory bowel disease (VEOIBD) is defined as disease onset in patients younger than 6 years. Challenges in treatment of VEOIBD include lack of approved therapies and increased incidence of monogenic immunodeficiencies. We report on patterns of anti-TNF use, efficacy, and safety in a large cohort of patients with VEOIBD.
Very early onset inflammatory bowel disease patients receiving care at a single center were prospectively enrolled in a data registry and biorepository starting in 2012. Whole exome sequencing was available to all patients. Clinical data including IBD medication use and response were extracted from the medical record. We examined antitumor necrosis factor (anti-TNF) cumulative exposure and time to failure and evaluated the effect of covariates on anti-TNF failure using Cox proportional hazard regression.
In this cohort of 216 VEOIBD patients with median 5.8-year follow-up, 116 (53.7%) were TNF-exposed. Sixty-two TNF-exposed patients (53.4%) received their first dose at younger than 6 years. Cumulative exposure to anti-TNF was 23.6% at 1 year, 38.4% at 3 years, and 43.4% at 5 years after diagnosis. Cumulative exposure was greater in patients with Crohn's disease (P = .0004) and in those diagnosed in 2012 or later (P < .0001). Tumor necrosis factor failure occurred in 50.9% of those exposed. Features predictive of anti-TNF failure included ulcerative colitis/IBD-unclassified (hazard ratio, 1.94; P = .03), stricturing (hazard ratio, 2.20; P = .04), and younger age at diagnosis (hazard ratio, 1.25; P = .01). Adverse events occurred in 22.6% of infliximab-exposed and 14.3% of adalimumab-exposed.
Efficacy and safety of anti-TNFs in VEOIBD is comparable to what has previously been reported in older patients.
非常早发性炎症性肠病（VEOIBD）的定义是患者在 6 岁以下发病。VEOIBD 治疗面临的挑战包括缺乏批准的治疗方法和单基因免疫缺陷病发病率的增加。我们报告了在一个大型 VEOIBD 患者队列中抗 TNF 药物的使用、疗效和安全性模式。
自 2012 年起，在一家单中心接受治疗的非常早发性炎症性肠病患者前瞻性地入组了一个数据登记和生物标本库。所有患者均进行全外显子组测序。从病历中提取包括 IBD 药物使用和反应在内的临床数据。我们检查了抗肿瘤坏死因子（抗 TNF）的累积暴露和失败时间，并使用 Cox 比例风险回归评估了协变量对抗 TNF 失败的影响。
在这个中位随访时间为 5.8 年的 216 名 VEOIBD 患者队列中，116 名（53.7%）患者接受了 TNF 治疗。62 名 TNF 暴露患者（53.4%）在 6 岁以下接受了首剂治疗。诊断后 1 年、3 年和 5 年时抗 TNF 的累积暴露分别为 23.6%、38.4%和 43.4%。在克罗恩病患者（P =.0004）和在 2012 年或以后诊断的患者（P <.0001）中，累积暴露更大。暴露组中 50.9%的患者发生了抗 TNF 失败。抗 TNF 失败的预测因素包括溃疡性结肠炎/未分类 IBD（风险比，1.94；P =.03）、狭窄（风险比，2.20；P =.04）和诊断时年龄较小（风险比，1.25；P =.01）。英夫利昔单抗暴露组和阿达木单抗暴露组的不良事件发生率分别为 22.6%和 14.3%。
VEOIBD 中抗 TNF 的疗效和安全性与以往报道的老年患者相似。
