COMMENTARY

Can't-Miss Highlights From ACG 2023: Part 1

David A. Johnson, MD

Disclosures

November 10, 2023

This transcript has been edited for clarity.

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

I'm just back from the American College of Gastroenterology (ACG) Annual Scientific Meeting in Vancouver, Canada. It was a smashing success, with approximately 7500 people attending, including 5500 on site and the remainder remotely.

The science was so outstanding that I've chosen to break this overview into two different segments. The order of the discussion follows no particular prioritization. It's simply designed to make it a little easier for you to follow in snippets and keep this relatively short.

Intestinal Ultrasound for IBD

The first study I'd like to highlight was about monitoring inflammatory bowel disease using intestinal ultrasound, an evolving technology performed at the bedside in real time.[1]

This retrospective analysis comes to us from investigators at the University of Chicago Medicine, who followed patients at their clinic receiving upadacitinib and either undergoing routine intestinal ultrasound at their bedside or conventional management. Among patients undergoing intestinal ultrasound, clinical remission was defined by the measurement of bowel wall thickness ≤ 3 mm in the terminal ilium or the colon, and the absence of hyperemia by color Doppler signal.

The investigators reported that the average time to a major adjustment in medication — if needed — was 1 day in patients managed with intestinal ultrasound vs 17 days in the conventional management group. It was also shown that remission was achieved by those undergoing real-time assessment with intestinal ultrasound approximately 1 month sooner (27 days vs 55 days).

Intestinal ultrasound is something that you'll see more frequently in your institutions as it becomes more widespread. As this study shows, it's a simple and easy assessment that doesn't require radiation, with lots of advantages, that is ready for prime time.

Identifying Hereditary Genetic Cancer Predispositions

Investigators behind the next study[2] looked at the implementation of a digital risk assessment tool at US gastroenterology practices to identify those with potential inherited cancer susceptibility genes.

Normally, you'd expect 2%-4% of the population would have the genetic susceptibilities assessed here, such as Lynch syndrome. However, among patients in this practice who met the National Comprehensive Cancer Network criteria for genetic counseling and testing, 15.6% had some genetic abnormalities.

Profiles that we order because our patients have colon cancer may also yield information that requires further evaluation by their primary care doctors or subsequent onco-geneticists.

Services are available to assist with genetic testing and counseling. The ACG, in collaboration with Gastro Girl, Inc., offers the GI OnDEMAND support platform, which is something that you can take advantage of remotely.

Seladelpar's Expanded Therapy Designation

Seladelpar, a selective agonist for the peroxisome proliferator-activated receptor delta, has emerged as a promising therapy because of its anti-inflammatory effects. This is particularly useful as it relates to liver diseases. We know that bile acid metabolism is closely associated with the development of a number of liver diseases, from alcoholic to nonalcoholic fatty liver disease, primary biliary cholangitis, and sclerosing cholangitis.

Investigators from the randomized phase 3 ENHANCE study[3] looked at seladelpar treatment in patients with primary biliary cholangitis, with a particular focus on pruritus, which can be a very debilitating symptom of this disease. They monitored patients' response to serum interleukin-31, which is reported to be an effective marker of resolution or improvement of this sporadic symptom. They found that seladelpar had a very striking and highly significant effect.

Seladelpar was granted orphan drug status as a breakthrough therapy in 2019. Quite literally, the day after this presentation, it was granted an addendum to expand this to now reflect treatment of primary biliary cholangitis including pruritus.

In 2024, we can look for this drug to move forward to approval by the US Food and Drug Administration (FDA) in patients with cirrhosis or with compensated cirrhosis. It may get us around some of those issues we've seen in primary biliary cholangitis with use of obeticholic acid. This is a high-profile drug that I think will have a major effect once it's released.

Gut-Directed Cognitive-Behavioral Therapy Improves IBS Symptoms

Brain-gut behavioral therapies are recommended for irritable bowel syndrome, but we don't typically have the resources to provide them. It's estimated that 60% of gastroenterologists in the United States lack access to a GI psychologist. This is provided by some of the pathways offered in the GIQuIC Registry, so I recommend you take a look at that.

Using real-world user data, investigators studied an FDA-approved module called Mahana IBS. Investigators evaluated 699 patients and found that there was an approximately 40% increase in their chance of their symptoms improving.[4]  

Therefore, I recommend looking into these developmental brain-gut behavioral therapies, which include cognitive-behavioral therapy, gut-directed hypnotherapy, and mindfulness. We've seen these successfully applied to irritable bowel syndrome, functional diseases, and nonulcer dyspepsia. These are therapies that we really need to be embracing, because when our patients have access to them, it certainly improves their outcomes.

Missed Opportunities for Biopsy During Esophageal Food Impaction

When treating a patient for esophageal food impaction, the recommendation is to also perform biopsies to evaluate for eosinophilic esophagitis (EoE). Typically, endoscopists may want to do more when they're in there, but they worry about aspiration and may choose to get in and out. Nonetheless, the question remains, does biopsy lead to an incremental risk in those patients?

Investigators from the University in North Carolina conducted a retrospective analysis,[5] looking at a 7-year span of patients reporting with endoscopically confirmed esophageal food impaction. They found that in just 39% of cases were biopsies performed during the evaluation for EoE. Also, biopsies were performed in only 70% of cases where patients had mucosal findings or stricture suggestive of EoE.  

We have to recognize that if we don't perform the biopsy at this time, we're missing an opportunity because these patients sometimes don't return. Some studies suggest that a diagnosis of EoE can be delayed for up to 6 years.

This is something that can be done safely. It's ready and very actionable to implement in our practices. When you remove the foreign body, don't forget to take a couple of biopsies. I would recommend taking both distal and proximal samples for EoE evaluation.

Additional Data on EoE

There were two other studies of interest about EoE.

The first of these[6] was a safety and efficacy study of etrasimod, a selective sphingosine-1-phosphate (S1P) receptor modulator. This is a drug that you may know well from its recent approval for ulcerative colitis, but it's now being applied to EoE. S1P receptors are found on the surface membranes of the immune cells, T cells, and B cells.

Investigators assessed the potential for etrasimod for modulating that effect over 24 weeks and then followed by a maintenance phase beyond that. They found it was highly effective.

This is a phase 2 study, and I would expect to see further studies on this on the immediate horizon as it relates to histologic and symptomatic endpoints. It seems to offer an incredibly promising opportunity for another advance in EoE.

When it comes to the treatment of EoE, we have drugs that are available only for adults. For kids under 12 years of age, we don't really have any approved medications.

This led investigators[7] to look at using dupilumab, a human monoclonal IgG4 antibody that inhibits the interleukin-4 and interleukin-13 signaling that modulates the T-helper cells affecting the processing for antigens and allergens. Therefore, it makes a lot of sense why it works in EoE.

This is the first time it has been shown to provide a benefit in kids. The primary endpoints, both histologic and symptomatic, showed it to be highly effective. As a result, I would hope to see this available in the near future as an augmentation therapy in children under 12 years of age.

I'm going to stop there, and invite you to join me for part 2, where I'll offer more highlights from ACG 2023. Thanks for listening.

David A. Johnson, MD, a regular contributor to Medscape , is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease

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