COMMENTARY

13 Highlights From the American College of Gastroenterology's 2022 Meeting

David A. Johnson, MD

Disclosures

November 01, 2022

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 meeting, held this year in the fantastic city of Charlotte, North Carolina. Kudos to the ACG staff for doing a phenomenal job. This year was once again a hybrid meeting, although I think those that attended in person would agree that there was a feeling of tremendous enthusiasm about being back in the presence of our colleagues, seeing people for the first time in many years outside of Zoom calls, reconnecting, and listening to the best cutting-edge science. It was just incredible.

I'd like to share with you the highlights that I found to be the most provocative from ACG 2022.

Upadacitinib Shows Limited, Dose-Dependent Benefits in Ulcerative Colitis

First was a multicenter study[1] by Brian Feagan and colleagues looking at upadacitinib, a Janus kinase inhibitor currently approved for use in rheumatoid arthritis and psoriatic arthritis and being investigated for multiple other applications.

In this case, investigators conducted a post hoc analysis of its use in patients with ulcerative colitis who were randomized to receive placebo or upadacitinib at 15 mg or 30 mg and were followed for 52 weeks. Upadacitinib led to significant improvements when used in the 30-mg dose, and the clinical remission extension was about a month over the 15-mg dose.

The results are still not quite there yet in terms of what I'd expect for these agents, even though they extended the clinical disease remission. But nonetheless, I'd recommend reading the abstract.

Treating Dyspepsia With Virtual Reality

Another study looked at using virtual reality in the treatment of functional dyspepsia. Cognitive-behavioral therapy has been very effective in a variety of disease states, particularly in recent years with irritable bowel syndrome.

Investigators conducted a double-blind, randomized, controlled study[2] using a virtual reality headset with three different programs that participants could use vs a control group. They found significant improvements in the scores related to dyspepsia and quality-of-life outcomes.

I think cognitive-behavioral therapy will emerge more in our functional disease armamentarium going forward, but we'll need to stay tuned to this space.

The Advantages of High-Quality Index Colonoscopies

Next was a presentation by Dr Joseph Anderson and colleagues[3] looking at high-quality index colonoscopy for predicting risk reduction for advanced outcomes at 10 years for patients who had no adenoma or serrated polyps on their index exam.

They looked at 14,257 individuals from the New Hampshire Colonoscopy Registry. They found that the absolute risk for advanced outcomes was 4% with high-quality exams — meaning, with an adenoma detection rate of 25 or greater — compared with 6.7% if you had a low-quality exam.

I think it will be helpful if the investigators look at more standard current-day values of 40% for high-level adenoma detection and really push the quality issue. If that happens, I think we'll see sustained benefit here, because quality matters.

A Clear Need for Genetic Counselling in Young-Onset Colon Cancer

Investigators at the Cleveland Clinic had looked for quite some time at the issue of younger onset colon cancer.[4] In doing so, they noted that 1 in 5 patients with younger-onset colon cancer have pathogenic germline variants regardless of their family history. However, less than two thirds of patients at the Cleveland Clinic were being referred for genetic counseling and testing, which caused them to realize that they needed to do a better job.

When it comes to colorectal cancer before age 50, the guidelines suggest that all patients should be referred for a germline pathogenic variant evaluation. This is something that is not standardly done, even in a Center of Excellence like the Cleveland Clinic. This led the investigators to suggest that health systems should consider implementing pathways to mitigate the potential impact of under-referral.

Two Studies on Recently Approved Eosinophilic Esophagitis Treatment

There were two presentations[5,6] given by Dr Evan Dellon looking at dupilumab, which has now been approved for eosinophilic esophagitis (EoE). Dupilumab is a fully human monoclonal antibody that blocks a shared receptor component for interleukin-4 and interleukin-13, which are the key drivers for type 2 inflammation with EoE.

This team shared 24- and 52-week data showing that dupilumab was efficacious and sustained when administered in once-weekly dosing.

It's important to recognize these are all nonresponders to proton pump inhibitors. The majority also had been on a variety of other treatments, including steroids. These are patients who typically have more severe disease. Whether or not this newer agent needs to be used in mild disease remains to be seen. They'll certainly be more to follow on that question soon.

A Return to On-Demand Treatment for Nonerosive Reflux Disease

Next was a multicenter study[7] by Dr Ronnie Fass and colleagues looking at the use of vonoprazan, a competitive acid blocker approved in the United States for Helicobacter pylori but not yet for reflux disease.

This is an expanded phase 2, double-blind trial looking at patients with nonerosive reflux disease who received once-daily vonoprazan and were then randomized to receive either placebo or vonoprazan at 10 mg, 20 mg, or 40 mg on demand as needed. Patients could not take more than one dose of the study drug for 24 hours after a heartburn episode and could take no rescue antacids within 3 hours after taking the study drug.

Investigators showed there was a significant effect when patients were shifted to taking vonoprazan solely on demand, where it was highly effective at achieving the primary endpoint of complete and sustained resolution. Rapid onset within 3 hours was achieved by approximately 70% of patients receiving vonoprazan at the 40-mg dose.

That's something we can start to look at, as perhaps some patients don't want to take medications daily. There's still more to see regarding the frequency and ongoing use. But the take-home message is that on-demand treatment may be back for acid suppression.

Increasing Response with Risankizumab in Crohn's Disease

In a study of an inflammatory bowel medication, intravenous risankizumab, an anti-p19 interleukin-23 inhibitor that had been shown to be superior to placebo, Dr Mala Dubinsky presented 52-week follow-up data.[8] The outcomes focused on clinical and endoscopic improvements.

The data were good. The combined endoscopic response/clinical remission was 23% and 36% for the 180-mg and 360-mg doses, respectively, which is administered at induction by infusion and then by subcutaneous dosing.

So again, we're not looking at the best of the best, but we're seeing at least response in a class of therapy that may warrant further evaluation. Stay tuned.

Analyzing the Effects of Vedolizumab and Ustekinumab During Pregnancy

There were also new data from the Pregnancy Inflammatory bowel disease And Neonatal Outcomes (PIANO) Registry.[9] With her wonderful registry, Dr Uma Mahadevan has done great work looking at maternal and neonatal outcomes.

In this circumstance, they looked at vedolizumab and ustekinumab, where the data were either unavailable or conflicting. They found no increase in pregnancy- or infant-related complications with either [vedolizumab or ustekinumab] compared with no exposure to anti–tumor necrosis factor alpha drugs, thiopurines, or a combination of them. Interestingly, ustekinumab was associated with a lower rate of preterm birth and C-section.

The continued use of these medications appears safe in pregnancy.

Remaining Alert to Rituximab-Related Enteropathy

Next was an interesting study[10] from the University of Chicago looking at rituximab, which we know is a monoclonal antibody therapy directed at CD20-positive B lymphocytes and is increasingly used in both malignant and autoimmune conditions. A consequence of this treatment, however, is that it may result in hypogammaglobulinemia due to B cell depletion, which can cause gastrointestinal side effects.

Investigators looked in a retrospective fashion over a 13-year interval and found 10 patients with enteropathy. These are mostly patients with lymphoma, which is the most common indication for rituximab. They found that 70% had pathologic diagnosis consistent with common variable immune deficiency enteropathy. All of them received intravenous immunoglobulin drug therapy. Only two had symptomatic improvement, however, and others received prednisone, budesonide, infliximab, and vedolizumab, none of which led to clinical improvement. Ultimately, 60% required long-term parenteral nutrition.

The take-home message is to be aware of this rituximab-associated enteropathy, and certainly be aware that it's not necessarily responsive to the standard inflammatory bowel–type therapies. These patients may require long-term parenteral nutrition.

Two Novel Treatments for Clostridioides difficile

There were two studies relating to C difficile.

The first is an open-label study of RBX2660, which is an investigational microbiome-based live biotherapeutic administered via enema.[11]Treatment success, which was defined as remaining recurrence-free for 8 weeks after treatment, was achieved by approximately 75% of patients. Patients who responded were followed out to 6 months, at which point 84% remained C difficile recurrence–free.

There was a similar study called the ECOSPOR IV, a double-blind, placebo-controlled trial looking at SER-109, an oral therapy processed from acute spores.[12] This treatment was delivered by four capsules three times a day over 3 days. Patients received an induction with a bottle of magnesium citrate. This treatment showed a similar type of effectiveness, with 79% of patients free of C difficile recurrence at 24 weeks.

So, there's benefit to both treatments, which is certainly a relief to those who provide care for patients with C difficile.

There is also an implication here when it comes to biomic transfer products, which is something that we may be using in the short term as soon as these things are approved by the US Food and Drug Administration.

Significant Improvements With Bile Acid Sequestrants in Microscopic Colitis

The final study I'd like to highlight looked at bile acid sequestrants in microscopic colitis.

It was a very interesting presentation of findings from Dr Darrell Pardi and colleagues,[13] who identified 282 patients with microscopic colitis and treated with bile acid sequestrants at Mayo Clinic Rochester. Virtually all of them had been treated with another medication prior to this, including loperamide, budesonide, bismuth subsalicylate, or mesalamine. The most common bile acid sequestrant these patients received was cholestyramine (65%).

There was a significant improvement for most patients, with nearly 50% experiencing a complete response and 16% a partial response; 25% had no response. One third of those patients with a complete or partial response were still taking a concomitant medication; but, again, most patients improved.

Not all patients had bile acid testing beforehand, which I thought was interesting. There was no dosing effect as it relates to the bile acid sequestrants — meaning, you go to higher dosing, it had more efficacy. And of course, there were varying rates of baseline diarrhea severity and history of cholecystectomy prior to treatment, but none of those seem to matter when it comes to predicting response.

Therefore, the take-home message here is to think about bile acid sequestrants. We should remember the potential for bile acid malabsorption in microscopic colitis. Potentially, though, there's long-term risk reduction, and it's a far easier treatment compared with ongoing steroid exposure, so these are results I find actionable even today.

Hopefully these results provide some value to you, and I encourage you to go to the website for ACG 2022, where you can read these abstracts in full for more information.

I'm Dr David Johnson. Thanks for listening. See you next time.

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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