From the The Children's Hospital of Philadelphia, Department of Pediatrics, Philadelphia, PA.
the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
J Pediatr Gastroenterol Nutr. 2022 Nov 1;75(5):608-615. doi: 10.1097/MPG.0000000000003589. Epub 2022 Aug 17.
The primary aim of this study was to determine the proportion of pediatric Crohn disease (CD) subjects in sustained drug-free remission 52 weeks after stopping pharmacological therapy. We also aimed to explore the effects of the Crohn Disease Exclusion Diet (CDED) and microbiome composition on remission.
We performed a prospective study following 18 CD patients ages 13-21 years in deep clinical remission withdrawing from immunomodulator (n = 7) or anti-TNFα (n = 11) monotherapy at two tertiary care centers. Stool for calprotectin and microbiome analyses was collected over 52 weeks. Participants followed either the CDED or free diet after drug withdrawal. The primary endpoint was sustained relapse-free drug-free remission (calprotectin <250 µg/g) at 52 weeks.
Seventeen participants were followed through 52 weeks with 11 (64.7%) in sustained remission. There was no improvement in remission among participants following the CDED (5/9; 55.6%), P = 0.63. By 104 weeks, only 8 (47.1 %) participants remained off immunosuppressive therapies. Analysis of shotgun metagenomic sequence data revealed that taxonomic and gene function abundance in the gut microbiome was relatively stable for participants in remission and relapse. However, a predictive model incorporating gut microbial gene pathway abundance for amino sugar/nucleotide sugar metabolism and galactose metabolism from baseline samples predicted relapse at 52 weeks with 80% accuracy.
After withdrawal of immunomodulator or anti-TNFα monotherapy among a small cohort of pediatric CD subjects in deep remission, nearly 65% sustained remission at 52 weeks. Baseline microbiome alterations predicted relapse. Large prospective studies are needed to better understand outcomes after treatment de-escalation.
本研究的主要目的是确定在停止药物治疗 52 周后，小儿克罗恩病（CD）患者持续无药物缓解的比例。我们还旨在探讨克罗恩病排除饮食（CDED）和微生物组组成对缓解的影响。
我们在两家三级护理中心对 18 名年龄在 13-21 岁的深度临床缓解的 CD 患者进行了前瞻性研究，这些患者停用免疫调节剂（n=7）或抗 TNFα（n=11）单药治疗。在 52 周内收集粪便钙卫蛋白和微生物组分析。停药后，参与者遵循 CDED 或自由饮食。主要终点是在 52 周时持续无复发无药物缓解（钙卫蛋白<250μg/g）。
17 名参与者随访至 52 周，其中 11 名（64.7%）持续缓解。遵循 CDED 的参与者缓解情况无改善（5/9；55.6%），P=0.63。到 104 周时，只有 8 名（47.1%）参与者仍未接受免疫抑制治疗。 shotgun 宏基因组序列数据分析显示，缓解和复发参与者的肠道微生物组的分类和基因功能丰度相对稳定。然而，一个纳入基线样本中与氨基糖/核苷酸糖代谢和半乳糖代谢相关的肠道微生物基因途径丰度的预测模型，以 80%的准确率预测了 52 周时的复发。
在深度缓解的小儿 CD 患者中停止免疫调节剂或抗 TNFα 单药治疗后，近 65%的患者在 52 周时持续缓解。基线微生物组改变预测了复发。需要进行大型前瞻性研究，以更好地了解治疗降级后的结局。
