Outcomes Following Acute Severe Colitis at Initial Presentation: A Multi-centre, Prospective, Paediatric Cohort Study

Jasbir Dhaliwal; Dominique Tertigas; Nicholas Carman; Sally Lawrence; Jennifer C Debruyn; Eytan Wine; Peter C Church; Hien Q Huynh; Mohsin Rashid; Wael El-Matary; Colette Deslandres; Jeffrey Critch; Amanda Ricciuto; Matthew W Carroll; Eric I Benchimol; Aleixo Muise; Kevan Jacobson; Anthony R Otley; Bruce Vallance; David R Mack; Thomas D Walters; Michael G Surette; Anne M Griffiths

doi:10.1093/ecco-jcc/jjad143

Outcomes Following Acute Severe Colitis at Initial Presentation: A Multi-centre, Prospective, Paediatric Cohort Study

J Crohns Colitis. 2024 Feb 26;18(2):233-245. doi: 10.1093/ecco-jcc/jjad143.

Authors

Jasbir Dhaliwal^{1

2

3

4}, Dominique Tertigas⁵, Nicholas Carman¹, Sally Lawrence⁶, Jennifer C Debruyn⁷, Eytan Wine⁸, Peter C Church^{1

9}, Hien Q Huynh⁸, Mohsin Rashid¹⁰, Wael El-Matary¹¹, Colette Deslandres¹², Jeffrey Critch¹³, Amanda Ricciuto^{1

2}, Matthew W Carroll⁸, Eric I Benchimol^{1

2

9}, Aleixo Muise¹, Kevan Jacobson⁶, Anthony R Otley¹⁰, Bruce Vallance⁶, David R Mack¹⁴, Thomas D Walters¹, Michael G Surette^{5

15}, Anne M Griffiths^{1

2

9}

Affiliations

¹ SickKids IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
² Child Health and Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
³ Cincinnati Children's Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati, USA.
⁴ Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH, USA.
⁵ Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
⁶ B.C. Children's Hospital, Division of Gastroenterology, Hepatology and Nutrition, Vancouver, BC, Canada.
⁷ Alberta Children's Hospital, Section of Pediatric Gastroenterology, Hepatology and Nutrition, University of Calgary, Calgary, AB, Canada.
⁸ Stollery Children's Hospital, Division of Gastroenterology, Hepatology and Nutrition, Edmonton, AB, Canada.
⁹ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
¹⁰ IWK Health Centre, University of Dalhousie, Division of Gastroenterology, Hepatology and Nutrition, Halifax, NS, Canada.
¹¹ Winnipeg Children's Hospital, Department of Paediatrics, University of Manitoba, Winnipeg, MN, Canada.
¹² CHU Sainte-Justine, Department of Paediatrics, University of Montreal, Montreal, QC, Canada.
¹³ Janeway Children's Health and Rehabilitation Centre, Memorial University, St. John's, NFLD, Canada.
¹⁴ Children's Hospital of Eastern Ontario IBD Centre, Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada.
¹⁵ Department of Medicine, McMaster University, Hamilton, ON, Canada.

Abstract

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.

Keywords: Ulcerative colitis; paediatric acute severe colitis.

Publication types

Multicenter Study

MeSH terms

Adrenal Cortex Hormones / therapeutic use
Biological Products* / therapeutic use
Canada
Child
Cohort Studies
Colitis, Ulcerative* / diagnosis
Colitis, Ulcerative* / drug therapy
Female
Humans
Infliximab / therapeutic use
Male
Mesalamine / therapeutic use
Prospective Studies
RNA, Ribosomal, 16S
Steroids / therapeutic use
Treatment Outcome

Substances

Infliximab
RNA, Ribosomal, 16S
Mesalamine
Adrenal Cortex Hormones
Steroids
Biological Products

Grants and funding

27862/CAPMC/ CIHR/Canada