When PPIs Don't Work for Reflux, Surgery Beats Drugs

Maureen Salamon

June 05, 2018

WASHINGTON, DC — Fundoplication surgery works far better than continuous drug treatment for gastroesophageal reflux disease refractory to proton pump inhibitors (PPIs), as long as other conditions that can cause heartburn are carefully ruled out, a new study suggests.

"Fundoplication had fallen from favor with gastroenterologists, largely because it had been used inappropriately and can have bad side effects," said Stuart Spechler, MD, from the Baylor University Medical Center in Dallas. "But gastroenterologists have to appreciate that there is a role for invasive treatment in this disease."

Up to 40% of patients with reflux symptoms treated with PPIs deal with persistent symptoms, and there are few treatment options for this group, Spechler told the crowd of about 1800 people here at Digestive Disease Week 2018.

"We have to get out of the mindset that there's nothing we can do for these patients," he told Medscape Medical News. "We've been doing our patients somewhat of a disservice by not recommending reflux surgery when appropriate."

He and his colleagues recruited 366 patients with heartburn refractory to medical therapy from 10 Veterans Administration centers. However, rigorous screening determined that in 288 cases, the heartburn stemmed from another cause.

Just 78 patients — 21% of the original cohort — proceeded to randomization. Of these, 27 underwent laparoscopic Nissen fundoplication; 25 received active medical treatment with 20 mg of the PPI omeprazole twice daily plus up to 20 mg of baclofen three times daily or, in the case of baclofen failure, up to 100 mg of desipramine at bedtime; and 26 received placebo.

"The difference in treatment success rates at 1 year was dramatic," Spechler reported. Treatment success was defined as an improvement in the Gastroesophageal Reflux Disease–Health-related Quality of Life score from baseline of at least 50%.

In fact, the rate of success at 1 year was substantially higher in the fundoplication group than in the active treatment or placebo groups (66.7% vs 28.0% vs 11.5%).

"We were surprised," said Spechler. These patients had "already failed medical therapy when they came to us, and we didn't have a lot of valid options to offer them. But I wasn't at all convinced they were going respond to surgery either."

Nonreflux Disorders Causing Heartburn

The rigorous testing to exclude nonreflux disorders that can cause heartburn, such as eosinophilic esophagitis, achalasia, and heart or biliary disease — which PPIs don't always eliminate — included endoscopy with esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance with pH monitoring.

It was illuminating to see the small number of participants that remained after exclusion, Spechler said. "It's good to find out that reflux isn't the cause [of ongoing heartburn] in a lot of cases, so we don't end up doing an invasive procedure," he added.

Gastroenterologists should "understand the importance of a very complete, systematic workup, and shouldn't jump immediately to invasive therapy for patients with refractory, GERD-like symptoms," he pointed out.

The low number of participants who actually had PPI-resistant reflux is striking, said Ikuo Hirano, MD, from the Feinberg School of Medicine at Northwestern University in Chicago.

If a patient has ongoing symptoms while on PPI therapy, it makes sense to think of nonreflux causes of ongoing symptoms.

"The take-home message I got, which is an important message, is that the majority of patients who went into this trial labeled with refractory reflux did not have acid reflux as the cause of their symptoms," he told Medscape Medical News. "To translate that to clinical practice, if a patient has ongoing symptoms while on PPI therapy, it makes sense to think of nonreflux causes of ongoing symptoms."

However, for the participants who received active medical therapy, the medications combined with the low-dose PPI tend to induce sleepiness as a major adverse effect, making this a "practical limitation" of the study, Hirano explained.

And in the real world, patients would likely receive a higher dose of PPI before undergoing surgery. "I still have a little higher bar for sending patients to fundoplication," he said.

This research is particularly relevant to Peter Ernst, PhD, DVM, from the University of California, San Diego, who takes a PPI medication for reflux.

"I think the message is clear that if you're not responding to medical therapy, go to a surgical approach," Ernst told Medscape Medical News. "GERD can be quite annoying. I think most people would consider a two-thirds improvement a reasonable outcome."

Spechler is a consultant for Takeda and Ironwood. Hirano and Ernst have disclosed no relevant financial relationships.

Digestive Disease Week (DDW) 2018: Abstract 615. Presented June 4, 2018.

Follow Medscape Gastroenterology on Twitter @MedscapeGastro and Maureen Salamon @maureensalamon

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