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The Unique Disease Course of Children with Very Early onset-Inflammatory Bowel Disease
Judith R Kelsen1,2, Maire A Conrad1,2, Noor Dawany3
1Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia.
Insights
Very early onset-inflammatory bowel disease (VEO-IBD) is linked to more severe outcomes, including increased surgeries and growth failure, compared to later-onset IBD. Targeted therapies show promise for improving VEO-IBD patient outcomes.
Area of Science:
- Pediatric Gastroenterology
- Inflammatory Bowel Disease Pathogenesis
- Clinical Outcomes Research
Background:
- Understanding the clinical course of very early onset-inflammatory bowel disease (VEO-IBD) is crucial, especially given identified monogenic defects in some patients.
- Previous research has not fully elucidated whether VEO-IBD presents with a more severe disease trajectory than inflammatory bowel disease (IBD) diagnosed at older ages.
- This study aims to clarify the clinical severity of VEO-IBD.
Purpose of the Study:
- To determine if VEO-IBD is associated with more severe disease, defined by increased surgical intervention and growth failure, compared to intermediate-onset and older-onset pediatric IBD.
- To evaluate secondary outcomes including therapeutic response and hospitalization rates in VEO-IBD patients.
- To compare clinical characteristics and outcomes across different age-of-onset groups for pediatric IBD.
Main Methods:
- A comparative study design involving subjects with IBD diagnosed younger than 6 years (VEO-IBD), 6 to 10 years (intermediate-onset), and older than 10 years (older-onset).
- Retrospective data collection from medical records, including age of onset, disease phenotype, location, surgical history, medical therapies, and comorbidities.
- Follow-up duration of at least 1 year from diagnosis to assess outcomes.
Main Results:
- VEO-IBD patients (n=229) experienced significantly more diverting ileostomies and colectomies compared to older-onset IBD patients (n=521).
- Subjects with VEO-IBD exhibited less improvement in weight- and height-for-age Z scores and higher rates of medication failure at 1 year.
- VEO-IBD patients had increased hospital readmissions and showed successful utilization of targeted therapy, which was used almost exclusively in this group.
Conclusions:
- VEO-IBD is associated with a more severe clinical course, characterized by increased surgical interventions and impaired growth, relative to older-onset IBD.
- VEO-IBD patients are more prone to refractory disease and poor response to conventional therapies.
- Targeted therapy strategies offer potential for improved outcomes and curative effects in select VEO-IBD cases.
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.
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