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在东南亚一组克罗恩病儿童中,采用独家肠内营养并同时早期使用硫唑嘌呤在维持无类固醇缓解方面是有效的。

Exclusive enteral nutrition with concomitant early thiopurine use was effective in maintaining steroid-free remission in a Southeast Asian cohort of children with Crohn's disease.

作者信息

Ong Christina, Lim Poh Ting, Logarajah Veena, Liwanag Maria Janelle, Ang Bi Xia, Cher Yuqin, Chiou Fang Kuan, Kader Ajmal

机构信息

Gastroenterology Service, Department of Paediatric Medicine, KK Women's and Children's Hospital, KK Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

出版信息

BMC Gastroenterol. 2018 Dec 12;18(1):185. doi: 10.1186/s12876-018-0907-7.

Abstract

BACKGROUND

Exclusive enteral nutrition (EEN) is as effective as corticosteroids in inducing remission in children with Crohn's disease (CD). However, over 50% of these children relapse by 12 months of diagnosis. Thiopurines are commonly prescribed as maintenance therapy for CD, but evidence for its efficacy is controversial. Data on the effectiveness of EEN in Southeast Asian (SEA) children with CD is scarce. This study aims to evaluate the efficacy of EEN induction therapy in a cohort of SEA children with newly diagnosed CD. The secondary aim was to evaluate concomitant early azathioprine (EAZ) use in determining remission rate at 6 and 12 months.

METHODS

Case records of all children with newly diagnosed CD from 2011 to 2014 were reviewed and relevant demographic as well as clinical data were extracted. The primary outcome measure was the number of patients who completed EEN induction therapy and achieved remission (Paediatric Crohn's Disease Activity Index; PCDAI≤10). Factors influencing duration of remission were evaluated in particular early azathioprine (EAZ) defined as starting azathioprine within one month of diagnosis versus late azathioprine (LAZ) use.

RESULTS

Forty children with newly diagnosed CD were identified. Thirty-three children: 67% boys, median age 13y (range 3-17) completed 8 weeks of EEN induction therapy and 91% achieved remission. Significant improvements were seen in PCDAI scores (32.7 ± 9.2 to 4.2 ± 5.1; p < 0.001), mean BMI z-score (- 1.38 ± 1.57 to - 0.82 ± 1.27; p = 0.004) and baseline inflammatory markers: Erythrocyte Sedimentation Rate (51.6 ± 30.1 mm/h to 13.3 ± 7.1 mm/h; p < 0.0001) C-Reactive Protein (44.6 ± 51.0 mg/L to 5.2 ± 7.6 mg/L; p = 0.001), Albumin (30.7 ± 7.5 g/L to 38.7 ± 3.9 g/L; p < 0.0001), Platelets (464 ± 161 × 10 to 370 ± 111 × 10; p < 0.0001),. Early azathioprine initiation was associated with a remission rate of 80 and 73% at 6 and 12 months respectively. Remission was also maintained for longer duration in EAZ vs LAZ groups (p = 0.048).

CONCLUSION

EEN effectively induces remission in this cohort of SEA children with newly diagnosed CD. Early initiation of thiopurine with EEN induction therapy is effective in maintaining steroid-free remission for at least one year.

摘要

背景

在诱导克罗恩病(CD)患儿缓解方面,全肠内营养(EEN)与皮质类固醇同样有效。然而,超过50%的此类患儿在诊断后12个月内复发。硫唑嘌呤通常被用作CD的维持治疗药物,但其疗效证据存在争议。关于EEN对东南亚(SEA)CD患儿有效性的数据很少。本研究旨在评估EEN诱导疗法对一组新诊断的SEA CD患儿的疗效。次要目的是评估同时使用早期硫唑嘌呤(EAZ)对6个月和12个月缓解率的影响。

方法

回顾了2011年至2014年所有新诊断CD患儿的病例记录,并提取了相关人口统计学和临床数据。主要结局指标是完成EEN诱导治疗并实现缓解的患者数量(儿童克罗恩病活动指数;PCDAI≤10)。特别评估了影响缓解持续时间的因素,早期硫唑嘌呤(EAZ)定义为在诊断后1个月内开始使用硫唑嘌呤,与晚期硫唑嘌呤(LAZ)的使用情况进行对比。

结果

确定了40例新诊断的CD患儿。33例患儿(67%为男孩,中位年龄13岁(范围3 - 17岁))完成了8周的EEN诱导治疗,91%实现了缓解。PCDAI评分(从32.7±9.2降至4.2±5.1;p < 0.001)、平均BMI z评分(从 - 1.38±1.57降至 - 0.82±1.27;p = 0.004)以及基线炎症标志物均有显著改善:红细胞沉降率(从51.6±30.1mm/h降至13.3±7.1mm/h;p < 0.0001)、C反应蛋白(从44.6±51.0mg/L降至5.2±7.6mg/L;p = 0.001)、白蛋白(从30.7±7.5g/L升至38.7±3.9g/L;p < 0.0001)、血小板(从464±161×10降至370±111×10;p < 0.0001)。早期开始使用硫唑嘌呤在6个月和12个月时的缓解率分别为80%和73%。与LAZ组相比,EAZ组的缓解维持时间也更长(p = 0.048)。

结论

EEN能有效诱导这组新诊断的SEA CD患儿缓解。EEN诱导治疗时早期开始使用硫唑嘌呤可有效维持至少一年的无类固醇缓解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df14/6292012/b96d3f40f893/12876_2018_907_Fig1_HTML.jpg

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