Debates tackle clinical relevance of GI disorders

All rise, the court is now is session to consider the longstanding clinical conundrums of ineffective esophageal motility (IEM) and eosinophilic esophagitis (EoE).

The two conditions underwent debates about their clinical relevance and best treatment practices in a “trial” between experts as part of Digestive Disease Week's virtual meeting, held online in May.

Experts offered their prosecution and defense of the issues, with a moderator acting as judge by offering a summary of clinical best practices during the meeting's Donald O. Castell, MD, Lecture: Controversies in Esophageal Disorders.

Case Docket No. 1: IEM

Defending the clinical relevance of IEM was Philip O. Katz, MD, a professor of medicine at Weill Cornell Medicine in New York City, who pleaded his case to the jury of virtual attendees.

“Remember, manometric abnormalities are based on a variation from normal asymptomatic volunteers who have not had an operation or an intervention,” Dr. Katz said. “If you're on the list of abnormalities, it's hard to call an abnormal finding clinically irrelevant. So point one: It's a named abnormality; it must have some clinical relevance.”

There are no biomarkers for esophageal motility disorders, “and in medicine, in general, a test does not always define the disease,” he said, offering the examples of gallstones or hiatal hernias that do not need to be fixed, yet play a role in the patient's clinical outcome.

Dr. Katz added that patients tend to appreciate a diagnosis. “[If] you tell them that their esophagus doesn't squeeze hard or the bolus doesn't move and that they feel it moving slowly, I think they do better,” he said. “I think they always do better if you give them a name for the symptom.”

But the definition of IEM has evolved over the years, measured initially by conventional manometry and distal amplitudes, then by contraction amplitudes, distal contractile intervals, and percentages of ineffective swallows, “all done in an attempt to refine the wastebasket diagnosis of nonspecific esophageal motility disorders,” Dr. Katz said.

Only time will tell how much and how often IEM is relevant, and ultimately, it requires a better definition than the current one, he said.

“Motility disorders and symptoms evolve over time. This is not a static business. So ultimately, in most cases, clinical judgment is the final arbiter as to the relevance of any abnormality in the patient in front of you,” he said.

The defense rests. On to the prosecution. Peter J. Kahrilas, MD, the Gilbert H. Marquardt Professor of Medicine at Northwestern University in Chicago, presented the con viewpoint that IEM is clinically irrelevant.

Like Dr. Katz, Dr. Kahrilas noted that the diagnosis has evolved. Future definitions could increase the percentage of ineffective swallows, include the concept of contraction reserve, “and there may even be a meal challenge invoked before this is viewed to be clinically relevant,” he said.

Dr. Kahrilas noted previous efforts to determine the condition's clinical relevance, including a symposium convened at Stanford in 2018.

Key points from the symposium include the concept that IEM is a heterogeneous, minor esophageal motor disorder not consistently associated with symptoms or disease, which can also occur in asymptomatic controls. It can be subcategorized with provocative tests, such as multiple repetitive swallows; a more extreme form of the condition would be in the setting of 70% or more failed test swallows.

However, there's no specific management available for IEM, and there's no pharmacological treatment that restores contractility or improves symptoms. Further, dysphagia is not perceived with incomplete esophageal bolus transit. Obstruction and pressurization are key to perceived dysphagia. When bolus transit is perceived, it is usually indicative of hypersensitivity, Dr. Kahrilas said, concluding that IEM is clinically irrelevant. “Bottom line: It's asymptomatic, and you can't do anything about it anyway.”

The debate's moderator, Stuart Jon Spechler, MD, chief of the division of gastroenterology and co-director of the Center for Esophageal Diseases at Baylor University Medical Center at Dallas, offered his summary judgment. He began by reiterating the ever-changing definition of IEM.

“When we compare studies on IEM, it's important to appreciate how much the diagnostic criteria have changed since 1997, when the condition was first described,” Dr. Spechler said. “It's also important to appreciate how heterogeneous this condition is. … Clearly, all IEM is not created equal.”

While IEM can be found in healthy asymptomatic individuals, it can also be associated with dysphagia and with gastroesophageal reflux disease, which might be treated surgically, he said. Preoperative IEM does not reliably predict dysphagia after surgery, and IEM can appear after antireflux operations. Finally, there's no clearly effective treatment for IEM, so even with an accurate diagnosis, the physician can't do very much about it, Dr. Spechler said.

“So is ineffective esophageal motility clinically relevant?” he asked. “Well, I can give you a definite perhaps; in some patients it appears to be relevant, and in others, it clearly is not.”

Case Docket No. 2: EoE

The next debate covered another longstanding conflict, whether maintenance therapy is needed for EoE, with the defense coming from Alain Schoepfer, MD, an associate professor of gastroenterology at Lausanne University Hospital and the University of Lausanne in Switzerland.

Dr. Schoepfer compared not treating EoE to “free solo” rock climbing, the practice of not using ropes or other safety measures. “If you do not want your EoE patients to do free solo climbing,” he said, “then you should definitely install a safety rope. And the safety rope ought to be our maintenance therapy.”

He emphasized that untreated EoE leads to esophageal stricture formation in roughly one-third of untreated patients after 10 years, which poses a major risk for ongoing symptoms. In addition, continuous maintenance therapy can dramatically reduce the risk of infection. The natural risk of ongoing fungal infections is 9% in those who do not take maintenance therapy, compared to less than 2% of patients who adhere to therapy, Dr. Schoepfer said.

“However, you're aware that there is not only white and black in life, but there are many gray zones,” he said. “So in this sense, I would like to discuss with you some of the challenges we are facing when prescribing chronic maintenance therapy.”

Surveillance of patients on chronic maintenance therapies shows that they are sometimes difficult to motivate to undergo regular endoscopic and histologic follow-up, Dr. Schoepfer said. Another issue involves long-term treatment adherence, particularly when patients are asymptomatic.

Treatment end points are relevant for patients because they strongly determine treatment adherence, he added. “Patients in the short term, but also in the long term, are very focused on improvement of their symptoms and of the quality of life, and they are less keen on their having an improvement on biologic end points, such as improvement of histological activity and/or endoscopic activity,” Dr. Schoepfer said.

Monitoring patients on chronic maintenance therapy can be cumbersome because physicians have to invite them repetitively for ongoing biopsies, he added, and practices should apply less invasive monitoring options.

Jeffrey A. Alexander, MD, a gastroenterologist at the Mayo Clinic in Rochester, Minn., countered that PPIs, steroids, or dietary restrictions may not be needed for all patients with EoE.

“I think there's a group of patients who have a flare of symptoms after successful acute treatment,” Dr. Alexander said. “I don't think there's any argument these people are going to need long-term therapy to control for symptoms. The group that I would debate is the group that has no flare of symptoms after successful acute treatment.”

He noted that progressive fibrotic disease related to diagnostic delay has been shown only in patients who eventually present for medical care, often after a period of years. “So the scenario here is we have patients with trivial or no symptoms, they advance to mild symptoms, maybe more symptoms and fibrotic chronic disease, then they present to the doctor. And here's where we find the high stricture rate,” Dr. Alexander said.

For every person treated for EoE in the U.S., there could be two dozen with EoE who have mild or minimal symptoms that never brought them to the doctor, he noted. There also may be a subgroup of patients with EoE who have a mild or less progressive form of disease, Dr. Alexander said.

Data showing a very high stricture rate over time may not represent the entire EoE population, he concluded, adding that survey data support a more benign course in many patients. Steroid and/or dietary therapy can be expensive, and steroids can be inconvenient, factors that lead to adherence issues and a high failure rate with long-term therapy, said Dr. Alexander.

“And finally, if one chooses no treatment and we go on to develop aggressive fibrotic disease, it can be safely and easily treated with esophageal dilation, and then long-term maintenance therapy can be initiated,” he said.

Again, Dr. Spechler ruled on the topic. Treatment reduces the rates of both symptom and histologic recurrence, he said. In addition, controlling EoE inflammation potentially reduces the risks of stricture formation and food impaction, although that has not been established by prospective studies, he noted.

That being said, the cost of these treatments can be a barrier, especially for steroid preparations, Dr. Spechler added. “Those topical steroids can be very expensive, they're inconvenient, and with no FDA approval, insurance companies might not cover the costs of topical steroid treatment. These medications can have side effects,” he said.

Furthermore, he said some patients lose treatment response when these medications are given long-term. Long-term therapy also has unproven benefits for patients with mild EoE disease phenotypes, who might do just fine with only intermittent treatment.

“So is maintenance therapy needed for eosinophilic esophagitis? I think we can say yes—for patients with severe disease phenotypes,” he concluded. “But for patients with mild disease phenotypes, I think you can only get a definite perhaps.”