新诊断为克罗恩病儿童复杂疾病病程的预测：一项多中心发病队列研究。
Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study.
机构信息
Division of Pediatric Gastroenterology, Emory University School of Medicine, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA.
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
出版信息
Lancet. 2017 Apr 29;389(10080):1710-1718. doi: 10.1016/S0140-6736(17)30317-3. Epub 2017 Mar 2.
BACKGROUND
Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown.
METHODS
We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk.
FINDINGS
Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51-82) and specificity of 63% (55-71), with a negative predictive value of 95% (94-97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10-0·89; p=0·0296) but not stricturing complication (1·13, 0·51-2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12-2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%.
INTERPRETATION
Our findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy.
FUNDING
Crohn's and Colitis Foundation of America, Cincinnati Children's Hospital Research Foundation Digestive Health Center.
背景
狭窄和穿透性并发症在儿科和成人发病的克罗恩病中导致了大量的发病率和医疗保健费用。目前尚无有效的预测并发症风险的模型，也不清楚治疗对风险的影响。
方法
我们在美国和加拿大的 28 个地点进行了一项新诊断的克罗恩病儿科患者的前瞻性发病队列研究。评估了基因型、抗菌血清学、回肠基因表达以及回肠、直肠和粪便微生物群。在独立的研究组中，建立并验证了一种用于疾病并发症的竞争风险模型。倾向评分匹配测试了诊断后 90 天内抗肿瘤坏死因子 α（TNFα）治疗暴露对并发症风险的影响。
结果
在 2008 年 11 月 1 日至 2012 年 6 月 30 日期间，我们招募了 913 名患者，其中 78 名（9%）经历了克罗恩病并发症。验证的竞争风险模型包括年龄、种族、疾病部位和抗菌血清学，并提供了 66%（95%CI 51-82）的敏感性和 63%（55-71）的特异性，阴性预测值为 95%（94-97）。接受早期抗 TNFα 治疗的患者发生穿透性并发症的可能性较低（风险比 [HR] 0.30，95%CI 0.10-0.89；p=0.0296），而不是狭窄性并发症（1.13，0.51-2.51；0.76）。与未接受早期抗 TNFα 治疗的患者相比，Ruminococcus 与狭窄性并发症有关，而 Veillonella 与穿透性并发症有关。在诊断时，控制细胞外基质产生的回肠基因上调，该基因特征与风险模型中的狭窄性有关（HR 1.70，95%CI 1.12-2.57；p=0.0120）。当包含该基因特征时，模型的特异性提高到 71%。
结论
我们的研究结果支持在诊断时对克罗恩病患儿进行风险分层，并选择抗 TNFα 治疗。
资助
美国克罗恩病和结肠炎基金会、辛辛那提儿童医院研究基金会消化健康中心。
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