Pediatric IBD Research Focused on Prevention and Prediction in 2020
Research published during 2020 on inflammatory bowel disease (IBD) in pediatric patients focused on two major themes: preventing the development of IBD in children, and identifying predictors of response to therapy among younger patients, Anne Griffiths, MD, said at the Advances in Inflammatory Bowel Diseases (AIBD) 2020 Virtual meeting.
Dr Griffiths is co-lead of the IBD Center and holds the Northridge Chair in IBD at the Hospital for Sick Children in Toronto, Ontario, Canada.
She referenced an “elegant study with 5 million person-years of information” published in Gastroenterology this year, on Empiric Dietary Inflammatory Pattern (EDIP) scores in pediatric participants. Results to date show that an EPID is associated with an increased risk of Crohn disease (CD) developing in children, although this does not appear to be the case with ulcerative colitis (UC). “Perhaps this is something we can give to our patients—the information to help prevent IBD rather than just controlling it once it has set in,” Dr Griffiths stated.
The Canadian GEM Study, which has been ongoing for 20 years, has enrolled some 5000 healthy children considered at genetically at risk for IBD due to having siblings or parents with CD or UC. “We are now in the position of being able to do a nested cohort study comparing those who developed Crohn disease—now about 90 individuals—with those who remained healthy.” The first publication of the GEM study, recently published in Gastroenterology, looked at participants’ intestinal permeability at enrollment. “As was shown in this paper, elevated intestinal permeability was associated with a greater risk of developing Crohn disease in this cohort.”
Noting that this study is just one of many, Dr Griffiths said, “the idea is that when you pool together some of the observations at to what ‘high risk’ means, this might set the stage for an interventional trial — specifically a dietary trial— aimed at reducing the development of IBD in high-risk people.”
Turning from attempts to prevent IBD to attempts to predict clinical response to therapeutic agents, Dr Griffiths noted the international initiative, the Pediatric Inflammatory Bowel Disease Network (PIBD-Net), published “a very rigorous systematic review and meta-analysis of existing evidence that would allow us to determine what are the predictors of severe outcomes.”
Many outcomes were examined and 54 statements were developed related to prediction of clinical course. “What is disappointing is that only 6 statements concern true biomarkers—specifically antimicrobial serology and NOD2 polymorphisms,“ Dr Griffiths noted. “So at the moment we really don’t have good biomarker predictors; this is still something that’s very much needed.”
The likelihood of IBD being a single gene disorder “or phenocopy of complex IBD, is related to the severity of phenotype in addition to the age of onset,” Dr Griffiths explained. The European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) will soon publish a position paper “which I think will bring some greater clarity to the question of who among our patients with the onset of IBD at a young age should be investigated for monogenic forms of IBD—what are the predictors?” she said.
A study in which Dr Griffiths participated conducted “whole exome sequencing of 67 genes known to be associated with monogenic IBD” among 1096 pediatric patients in Toronto with a mean age of 11 years. Of the children studied, she said, “3% had a variant in one of these 67 genes.” Age at onset was also a factor, she added, particularly children aged 2 years or younger.
On the topic of treatment for pediatric IBD, Dr Griffiths explained that ESPGHAN along with the European Cancer Organization (ECCO) this year updated their guidelines on treatment of pediatric CD “with an emphasis on recognizing and identifying patients with IBD at high risk of severe disease” and using anti-tumor necrosis factor (TNFs) agents early in treatment. She noted that other research has shown an association between early induction with anti-TNFs and a higher likelihood of clinical remission and endoscopic healing in adults and children.
“If we use anti-TNFs early, what are our exit strategies?” Dr Griffiths asked. She described a study published in Gut in which researchers investigate the potential of certain protein biomarkers to predict which patients are likely to remain in remission of IBD after de-escalation of therapy.
Dr Griffiths praised “the remarkable speed” with pediatric and adult gastroenterologists collaborated to establish SECURE-IBD in response to the onset of the COVID-19 pandemic and its implications for patients with IBD. “It has only been through this database that we’ve been able to get some information on whether therapies we use to control IBD do or do not adversely affect outcomes and then to give guidance to our patients.”
Griffiths AM. Pediatric IBD year in review. Talk presented at: Advances in Inflammatory Bowel Diseases 2020 Virtual. December 12, 2020. Virtual