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Anti-Saccharomyces cerevisiae Antibodies as a Prognostic Biomarker in Children With Crohn Disease

Chandrakumar, Abin*,†,‡; Georgy, Michael; Agarwal, Prasoon*,§,||; ‘t Jong, Geert W.*,†,§,¶; El-Matary, Wael‡,¶

Journal of Pediatric Gastroenterology and Nutrition: July 2019 - Volume 69 - Issue 1 - p 82–87
doi: 10.1097/MPG.0000000000002311
Original Articles: Gastroenterology: Inflammatory Bowel Disease
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Objective: Although anti-Saccharomyces cerevisiae antibodies (ASCAs) could be a useful biomarker in differentiating Crohn disease (CD) from ulcerative colitis (UC), their role as prognostic markers in children with CD has been underinvestigated. This longitudinal prospective observational study aimed to assess the prognostic value of ASCA status among children with CD managed using biologics.

Methods: The study population comprised children with inflammatory bowel disease diagnosed with CD from 2012 to 2018. Cox regression model with adjustment for a priori covariates was used to examine the response to anti-tumor necrosis factor (TNF) biological therapy among ASCA-positive patients in comparison to ASCA-negative patients.

Results: There were 273 measurements available from the study cohort comprising children with CD, who were followed up for a median duration of 14 months (interquartile range 5–42). ASCA-positive patients had a higher risk for moderate to severe clinical disease (odds ratio 2.88; 95% confidence interval [CI] 1.2–7.55) and extensive endoscopic distribution (odds ratio 3.30; CI 1.12–9.74) at baseline in comparison to ASCA-negative patients, respectively. In comparison to ASCA immunoglobulin G (IgG)-negative patients, ASCA IgG–positive patients who were treated with biologics had a significantly lower relapse rate (adjusted hazard ratio 0.12; CI 0.02–0.93). Ten (14%) patients had an unstable ASCA value with either ASCA immunoglobulin A or ASCA IgG status changing from positive to negative or vice versa.

Conclusions: ASCA-positive children with CD present with more extensive (endoscopic) and clinically severe disease. ASCA IgG is a useful prognostic marker among children with CD who receive biologics.

*Department of Pharmacology and Therapeutics, University of Manitoba

Clinical Research Unit, Children's Hospital Research Institute of Manitoba

Section of Pediatric Gastroenterology, Winnipeg Children's Hospital, Max Rady College of Medicine, Rady Faculty of Health Sciences and Children's Hospital Research Institute

§Manitoba Developmental Origins of Chronic Diseases in Children Network (DEVOTION), University of Manitoba

||Diabetes Research Envisioned and Accomplished in Manitoba (DREAM), Children's Hospital Research Institute of Manitoba

Department of Pediatrics and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences and Children's Hospital Research Institute, Winnipeg, Manitoba, Canada.

Address correspondence and reprint requests to Wael El-Matary, MBBCh, MD, MSc, FRCPCH, FRCPC, Head, Section of Pediatric Gastroenterology, Professor, Department of Pediatric and Child Health, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, AE 408 Children's Hospital, Health Sciences Centre, 840 Sherbrook St, Winnipeg, MB R3A 1S1, Canada (e-mail: welmatary@exchange.hsc.mb.ca).

Received 20 October, 2018

Accepted 16 January, 2019

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org).

This study was supported through funding from the Children's Hospital Research Institute of Manitoba (CHRIM) and the Children's Hospital Foundation, Winnipeg. A.C. was supported by the Children's Hospital Research Institute of Manitoba graduate studentship (in collaboration with Research Manitoba) for the year 2017 to 2018. A.C. currently receives support from the Women's Health Research Foundation of Canada (WHRF) graduate scholarship for the year 2018 to 2019. P.A. is supported by the Manitoba Health Research Council (MHRC) post-doctoral fellowship.

Abin Chandrakumar and Michael Georgy Shared first authors.

W.E. served as an advisory board member for both Janssen, Canada and AbbVie, Canada. He also received research support for Janssen, Canada.

The remaining authors report no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.jpgn.org).

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,