Outcomes Following Acute Severe Colitis at Initial Presentation: A Multi-centre, Prospective, Paediatric Cohort Study
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Published on: July 12, 2018
Jasbir Dhaliwal1,2,3,4, Dominique Tertigas5, Nicholas Carman1
1SickKids IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
Insights
Most children with acute severe ulcerative colitis (ASUC) require advanced biologic therapies. Gut microbiome alterations and clinical factors predict the need for infliximab, guiding treatment selection.
Area of Science:
- Pediatric Gastroenterology
- Inflammatory Bowel Disease Research
- Microbiome Science
Background:
- Acute severe ulcerative colitis (ASUC) in children presents unique challenges in management and long-term outcomes.
- Understanding the initial presentation and treatment response is crucial for optimizing pediatric IBD care.
Purpose of the Study:
- To evaluate the outcomes of children with ASUC at their first presentation.
- To identify predictors for escalating therapy and long-term disease course.
Main Methods:
- Prospective follow-up of children (<17 years) with new-onset ASUC (Paediatric Ulcerative Colitis Activity Index [PUCAI] ≥65).
- Analysis of baseline fecal microbiome composition using 16S rRNA amplicon sequencing.
- Primary endpoint: corticosteroid-free clinical remission at 1 year.
Main Results:
- Of 105 children with ASUC, 51% were steroid-refractory and initiated infliximab; 61% achieved corticosteroid-free remission at 1 year.
- Gut microbiome in ASUC showed lower alpha-diversity, reduced beneficial anaerobes, and increased aerobes compared to mild UC.
- Hypoalbuminemia, higher PUCAI, older age, and male sex predicted the need for infliximab.
Conclusions:
- The majority of pediatric ASUC patients escalate therapy to biologics, often infliximab.
- Identifying predictors for advanced therapy can aid in selecting appropriate maintenance strategies for children with ASUC.
Aim:
To assess contemporary outcomes in children with acute severe ulcerative colitis [ASUC] at initial presentation.
Methods:
Between April 2014 and January 2019, children aged <17 years, with new onset ASUC (Paediatric Ulcerative Colitis Activity Index [PUCAI ≥65) were prospectively followed in a Canadian inception cohort study. 16S rRNA amplicon sequencing captured microbial composition of baseline faecal samples. Primary endpoint was corticosteroid-free clinical remission with intact colon at 1 year [PUCAI <10, no steroids ≥4 weeks].
Results:
Of 379 children with new onset UC/IBD-unclassified, 105 [28%] presented with ASUC (42% male; median [interquartile range; [IQR]) age 14 [11-16] years; extensive colitis in all). Compared with mild UC, gut microbiome of ASUC patients had lower α-diversity, decreased beneficial anaerobes, and increased aerobes; 54 [51%] children were steroid-refractory and given infliximab [87% intensified regimen]. Corticosteroid-free remission at 1 year was achieved by 62 [61%] ASUC cohort (by 34 [63%] steroid-refractory patients, all on biologics; by 28 [55%] steroid responders,13 [25%] on 5- aminosalicylic acid [5-ASA], 5 [10%] on thiopurines, 10 [20%] on biologics). By 1 year, 78 [74%] escalated to infliximab including 24 [47%] steroid-responders failed by 5-ASA and/or thiopurines. In multivariable analysis, clinical predictors for commencing infliximab included hypoalbuminaemia, greater PUCAI, higher age, and male sex. Over 18 months, repeat corticosteroid course[s] and repeat hospitalisation were less likely among steroid-refractory versus -responsive but -dependent patients (adjusted odds ratio [aOR] 0.71 [95% CI 0.57-0.89] and 0.54 [95% CI 0.45-0.66], respectively).
Conclusion:
The majority of children presenting with ASUC escalate therapy to biologics. Predictors of need for advanced therapy may guide selection of optimal maintenance therapy.
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