Background & Aims

The early stages of Crohn's disease (CD) course are heterogeneous, and it is a challenge to predict the course of disease in patients with new diagnosis.

Methods

We performed an observational longitudinal study of 156 adults (79 male; median age, 27.7 years; 57 treatment naïve) with newly diagnosed CD (within 6 months of enrollment), referred from medical centers and community clinics in Israel from 2013 through 2017. Study participants each received semi-annual scheduled evaluations. Indolent disease was defined as a disease course without need for strict interventions to control complicated course of CD (hospitalization or surgery, or decision to start steroid, immunomodulator, or biologic therapy). Cox regression and receiver operating characteristic analyses were used to identify factors associated with early indolent or complicated course of CD. We validated our findings in an independent cohort of patients with CD from a separate medical center in Israel in 2018.

Results

Over a median follow-up period of 17.2 months (interquartile range, 8.8–23.8 months), 52 patients (33.3%) had an indolent course of CD, 29 (18.5%) required hospitalizations, and 75 (48%) were recommended to start steroid, immunomodulator, or biologic therapies. The median time to first intervention was 3.4 months (95% CI, 2.4–4.4). We developed a model based on clinical factors that identified 4 factors associated with complicated course in treatment-naïve patients: body mass index <25 kg/m² (hazard ratio [HR], 2.45; 95% CI, 1.07–5.43; P = .033), serum level of vitamin B12 <350 pg/mL (HR, 2.78; 95% CI, 1.21–6.41; P = .016), white blood cells ≥7 × 10³/μL (HR, 2.419; 95% CI, 1.026–5.703; P = .044), and serum level of ALT ≥25 IU/L (HR, 2.680; 95% CI, 1.186–6.058; P = .018). This model discriminated between patients with vs without a complicated course of disease with 90% and 89% accuracy at 6 and 12 months after diagnosis, respectively. A validation cohort demonstrated a discriminatory ability of 79% at 3 months after diagnosis, and a nomogram was constructed.

Conclusions

In an observational longitudinal study of 156 patients with newly diagnosed CD, we found that one third have an early indolent course of disease. We identified factors that can be measured at diagnosis to identify patients at risk for an early complicated course—these might be used in patient management and selection of treatment.

中文翻译：

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新诊断的克罗恩病的早期惰性病程并不罕见并且可能是可预测的

背景与目标

克罗恩病 (CD) 病程的早期阶段具有异质性，预测新诊断患者的病程是一项挑战。

方法

我们对 2013 年至 2017 年从以色列医疗中心和社区诊所转诊的 156 名新诊断 CD（入组后 6 个月内）的成年人（79 名男性；中位年龄，27.7 岁；57 名初治）进行了一项观察性纵向研究。研究参与者每人接受半年一次的预定评估。惰性疾病被定义为不需要严格干预来控制复杂的 CD 病程（住院或手术，或决定开始类固醇、免疫调节剂或生物治疗）的病程。Cox 回归和受试者工作特征分析用于确定与早期惰性或复杂 CD 病程相关的因素。我们于 2018 年在以色列独立医疗中心的 CD 患者独立队列中验证了我们的发现。

结果

在 17.2 个月的中位随访期（四分位距，8.8-23.8 个月）中，52 名患者（33.3%）有惰性 CD 病程，29 名（18.5%）需要住院治疗，75 名（48%）被推荐开始类固醇、免疫调节剂或生物疗法。首次干预的中位时间为 3.4 个月（95% CI，2.4-4.4）。我们基于临床因素开发了一个模型，该模型确定了与初治患者复杂病程相关的 4 个因素：体重指数 <25 kg/m ²（风险比 [HR]，2.45；95% CI，1.07–5.43；P = .033)，血清维生素 B12 水平 <350 pg/mL (HR, 2.78; 95% CI, 1.21–6.41; P = .016 ), 白细胞≥7 × 10 ³ /μL (HR, 2.419; 95%置信区间，1.026–5.703；P =.044)，血清 ALT 水平≥25 IU/L (HR, 2.680; 95% CI, 1.186–6.058; P = .018 )。该模型在诊断后 6 个月和 12 个月时分别以 90% 和 89% 的准确率区分患有与不具有复杂病程的患者。一个验证队列在诊断后 3 个月表现出 79% 的鉴别能力，并构建了列线图。

结论

在一项对 156 名新诊断 CD 患者的观察性纵向研究中，我们发现三分之一的患者早期病程缓慢。我们确定了可以在诊断时测量的因素，以识别有早期复杂病程风险的患者——这些可能用于患者管理和治疗选择。