New Treatments Where We Desperately Need Them, and Other Noteworthy Data: DDW 2019

David A. Johnson, MD


June 25, 2019

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. At the recently concluded 50th annual Digestive Disease Week, several studies were presented that caught my eye, which I'd like to share with you now.

Fecal Transfer Capsules Prove Their Worth

First was a study of fecal microbiome transfer via oral capsules in cirrhotic patients with recurrent hepatic encephalopathy who were on standard of care. The study was performed by Bajaj and colleagues[1] at Virginia Commonwealth University, who randomized patients to receive placebo or 15 fecal microbial transplant capsules from a single donor. The capsules were all enriched with Lachnospiraceae and Ruminococcaceae, bacterial elements that they had noted to be relatively deficient in such patients. They looked at the endpoints of duodenal integrity and inflammation, recurrent hepatic encephalopathy, and hospitalizations, all of which improved notably in patients who received these capsules. Tolerability was good, and treatment led to improvement in diversity in the duodenum, dysbiosis, and barrier function, as well as enhanced encephalopathy parameters.

Vedolizumab Comes Out on Top in Head-to-Head Trial

Next was a head-to-head comparison study of two biologic therapies, vedolizumab versus adalimumab, in 769 patients with moderate to severe ulcerative colitis.[2] The study endpoints were mucosal healing and symptom recurrence. Notably, about 25% of the study patients were allowed to have prior tumor necrosis factor failures other than with adalimumab. The clinical response rate at week 14 was approximately 12% in favor of vedolizumab over adalimumab. When they looked at mucosal healing at 52 weeks, it was significantly improved with vedolizumab over adalimumab, again at approximately 12% (39.7% vs 27.7%). These results may change practice as it relates to induction and continuation of disease remission.

An Agonist on the Fast Track for Gastroparesis

Velusetrag is a 5-hydroxytryptamine receptor 4 agonist that has been studied in both the upper and lower gastrointestinal tract. Abell and colleagues[3] reported the effect of this agent in patients with idiopathic gastroparesis or well-controlled diabetic gastroparesis. They looked at composite endpoints at dose variants of 5 mg, 15 mg, and 30 mg of the study drug versus placebo. The study drug resulted in improvements in all symptom domains only at 5 mg, which is kind of interesting. But the really exciting thing was that normalization of gastric emptying at the end of 28 days in the 5 mg, 15 mg, and 30 mg groups was 44%, 65%, and 71%, respectively, and 0% for the placebo. I can't believe these numbers; they're off the chart. There will be more to follow, as this drug was fast-tracked by the US Food and Drug Administration a couple of years ago. We desperately need a drug in gastroparesis.

Two Studies Put the Focus on Proton Pump Inhibitors

Paul Moayyed and his group[4] offered a reassuring study on the side effects of proton pump inhibitors (PPIs). They looked at the composite of PPI exposure over 3 years in combination with aspirin and/or rivaroxaban for cardiac prevention in more than 17,000 patients with over 53,000 patient-years. There was no difference as it relates to the standard PPI consequences, with the exception of a slight rise in the odds of enteric infections.

It is estimated that persistent symptoms occur in approximately 30% of patients with gastroesophageal reflux disease (GERD) taking PPIs. Michael Vaezi and colleagues[5] conducted an industry-sponsored study looking at the impact of adding the bile acid sequestrant IW-3718 on individual GERD symptoms. They reported a statistical improvement in parameters related to heartburn and regurgitation. Interestingly, they noted that 10 other GERD-related symptoms also improved. Again, we'll need to wait and see what comes out of this promising phase 3 study, but we desperately need something in these PPI partial responders.

New Risks for Opiate Use

It is really important for you to pay attention to the next study, which looked at the association between opiate use and bile duct dilation in patients with normal liver function. We all know that opioid use has become a rampant problem in the United States, with prescriptions tripling over the past 20 years. Researchers[6] from Stanford University looked at their referral rate for endoscopic ultrasound/endoscopic retrograde cholangiopancreatography for bile duct dilation, which has gone up fivefold over the past decade. They found the association between opiate use and bile duct dilation to be particularly evident in patients with an intact gallbladder; in those who used opiates, bile duct diameter was 43.5% greater than in non–opiate users. In patients with cholecystectomy, opiate users had a 6.6% greater diameter than non–opiate users. We need to start to look at opiate use in patients. We screen out opioid users for esophageal motility, because you can see the same effect [from opioids] in the esophagus as it relates to hypercontractility.

When to Stop Surveillance for Barrett Esophagus

Elsewhere, there was an interesting study[7] on when to stop endoscopic surveillance of Barrett esophagus. Database experts looked at two independently developed European and US models, each calibrated to empiric US Surveillance, Epidemiology, and End Results cancer registry data. The bottom line is, the optimal age to stop surveillance in non-dysplastic Barrett esophagus without a comorbidity is 83 years. This is surprising to me, because it prevented 14% more cancer cases than stopping this surveillance earlier. If they had comorbidities, you'd stop up to 8 years earlier. This indicates that comorbidities must be taken into account when considering extending the time that we survey these patients.

Consequential Complications in Nonalcoholic Fatty Liver Disease

The last study[8] looked at the risk for hepatic progression in patients with nonalcoholic fatty liver disease (NAFLD). One of the study's coauthors was Dr Hashem B. El-Serag, who we should congratulate as well for being named the new president of the American Gastroenterological Association. He and his colleagues performed a retrospective cohort study of 13,159 patients (mean age, 65.6 years; 45.3% obese) with NAFLD at 130 facilities of the Veterans Administration. After a median follow-up of 7.6 years, a little less than one third developed cirrhosis complications, and approximately 40% died. At 5 and 10 years, the rate of cirrhosis complications was 17% and 27.5%, respectively, and the overall mortality was 21.7% and 47.2%, respectively. However, if you developed a complication, those latter numbers went up to 56% and 92%, respectively. So, complications really derail these patients when it comes to mortality. There were some co-factors that were more predictive, such as obesity, diabetes, and hypertension, which were independently related to the increased risk for cirrhosis complications. We need to be aware of these things and be more proactive in our evaluation, perhaps looking for more ways we can intervene to prevent some of these progressions in cirrhosis and monitoring these patients appropriately.

I wish a happy 50th anniversary to Digestive Disease Week. This year's meeting offered some exciting science that we'll be following up on in the months ahead. Hopefully some of these studies whet your appetite as to what's coming, and some may even offer practice-changing insights in the short term.

This is Dr David Johnson. Thanks again for listening.

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