Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study.
Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study.
复制标题
DOI：
10.1016/s0140-6736(17)30317-3
复制
发表时间：
2017-04-29
期刊：
影响因子：
--
通讯作者：
Dubinsky MC
中科院分区：
文献类型：
--
作者：
Kugathasan S;Denson LA;Walters TD;Kim MO;Marigorta UM;Schirmer M;Mondal K;Liu C;Griffiths A;Noe JD;Crandall WV;Snapper S;Rabizadeh S;Rosh JR;Shapiro JM;Guthery S;Mack DR;Kellermayer R;Kappelman MD;Steiner S;Moulton DE;Keljo D;Cohen S;Oliva-Hemker M;Heyman MB;Otley AR;Baker SS;Evans JS;Kirschner BS;Patel AS;Ziring D;Trapnell BC;Sylvester FA;Stephens MC;Baldassano RN;Markowitz JF;Cho J;Xavier RJ;Huttenhower C;Aronow BJ;Gibson G;Hyams JS;Dubinsky MC
在小儿和成人克罗恩病中，穿刺和穿透性并发症造成了大量的发病率和医疗保健费用。目前尚无预测并发症风险的有效模型，治疗对风险的影响也未知。我们在美国和加拿大的28个地点对新诊断的克罗恩病儿童患者进行了一项前瞻性初始队列研究。评估基因型、抗菌血清学、回肠基因表达以及回肠、直肠和粪便微生物群。疾病并发症的竞争风险模型，并在独立的群体中得到验证。倾向评分匹配检测了诊断后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。在2008年11月1日至2012年6月30日期间，我们招募了913例患者，其中78例（9%）发生了克罗恩病并发症。经验证的竞争风险模型包括年龄、种族、疾病部位和抗微生物血清学，灵敏度为66%（95%CI 51-82），特异性为63%（55-71），阴性预测值为95%（94-97）。与未接受早期抗TNF α治疗的患者相比，接受早期抗TNF α治疗的患者发生穿透性并发症（风险比[HR] 0·30，95% CI 0·10-0·89; p=0·0296）的可能性较低，但不发生狭窄性并发症（1·13，0·51-2·51; 0·76）。瘤胃球菌与狭窄并发症有关，韦荣氏球菌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，该基因标记与风险模型中的狭窄相关（HR 1.70，95%CI 1.12 - 2.57; p= 0.0120）。当包括这种基因签名时，模型的特异性提高到71%。我们的研究结果支持克罗恩病儿童患者在诊断时进行危险分层和选择抗TNF α治疗的有用性。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。
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. 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. 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%. Our findings support the usefulness of risk stratification of paediatric patients with Crohn’s disease at diagnosis, and selection of anti-TNFα therapy. Crohn’s and Colitis Foundation of America, Cincinnati Children’s Hospital Research Foundation Digestive Health Center.