Kelsen JR^1,2, Conrad MA^1,2, Dawany N³, Patel T^1,2, Shraim R¹, Merz A¹, Maurer K⁴, Sullivan KE^2,4, Devoto M^2,5,6. Inflamm Bowel Dis. 2019 Sep 27. pii: izz214. doi: 10.1093/ibd/izz214. [Epub ahead of print]

Author information

1 Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia.

2 Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania.

3 Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia.

4 Division of Immunology and Allergy, The Children's Hospital of Philadelphia.

5 Division of Human Genetics, The Children's Hospital of Philadelphia.

6 Department of Translational and Precision Medicine, University Sapienza, Rome, Italy.

Abstract

BACKGROUND: Insight into the pathogenesis of very early onset-inflammatory bowel disease (VEO-IBD) has expanded through the identification of causative monogenic defects detected in a subset of patients. However, the clinical course of this population remains uncertain. The study objective is to determine whether VEO-IBD is associated with more severe disease, defined as increased surgical intervention and growth failure, than older pediatric IBD. Secondary outcomes included therapeutic response and hospitalizations.

METHODS: Subjects with IBD diagnosed younger than 6 years old (VEO-IBD) were compared with children diagnosed 6 to 10 (intermediate-onset) and older than 10 years of age (older-onset IBD). Metadata obtained from the medical record included age of onset, disease phenotype and location, surgeries, medical therapy, and comorbid conditions. Length of follow-up was at least 1 year from diagnosis.

RESULTS: There were 229, 221, and 521 subjects with VEO, intermediate-onset, and older-onset IBD, respectively. Very early onset-inflammatory bowel disease subjects underwent more diverting ileostomies (P < 0.001) and colectomies (P < 0.001) than the older children. There was less improvement in weight- and height-for-age Z scores during the follow-up period in subjects with VEO-IBD. Additionally, subjects with VEO-IBD had higher rates of medication failure at 1 year and were more frequently readmitted to the hospital. Targeted therapy was successfully used almost exclusively in VEO-IBD.

CONCLUSION: Patients with VEO-IBD can have a more severe disease course with increased surgical interventions and poor growth as compared with older-onset IBD patients. Further, VEO-IBD patients are more likely to be refractory to conventional therapies. Strategies using targeted therapy in these children can improve outcome and, in some cases, be curative.