Best practices for gastroesophageal reflux disease in Asia-Pacific

The treatment of gastroesophageal reflux disease (GERD) continues to rely on proton pump inhibitors (PPIs), but advances in the field take account of new management options, such as antireflux surgery for reflux hypersensitivity and diaphragmatic breathing in refractory GERD or rumination, as pointed out during a lecture presented at this year’s virtual Asian Pacific Digestive Week (APDW 2021).

“The efficacy of PPIs depends on the GERD phenotype… They're very good for esophagitis and they're not bad for heartburn relief [as well as for] regurgitation, but there is a significant subgroup of patients with reflux disease whose symptoms do not respond to PPI therapy,” according to Dr Nicholas Talley from Hunter Medical Research Institute (HMRI) in Newcastle, Australia.     

In terms of potency, there are some PPIs that are less effective at acid suppression, Talley stated. For example, a 20-mg dose of esomeprazole or rabeprazole is more potent than omeprazole the same dose.

“If you compare the relative potency of PPIs and potassium competitive acid blockers, vonoprazan is more effective at suppressing acid compared with esomeprazole and rabeprazole, although in terms of clinical trial efficacy, these drugs really are remarkably similar and the differences are minor in terms of outcomes,” Talley said.

He also noted that while there's been a lot of discussion about the safety of PPIs in recent years, the drugs are very low-risk. Citing a trial evaluating the safety of pantoprazole vs placebo over 3 years, Talley noted the only safety signal that emerged was enteric infections (1.4 percent vs 1.0 percent; odds ratio, 1.33). [Gastroenterology 2019;157:682-691]

“There was no other statistically significant difference in safety events between pantoprazole and placebo identified in this trial. This is really level one evidence, so, our PPIs are remarkably safe, and that is important,” he said.

However, Talley noted that the management of refractory reflux remains problematic, as was discussed in detail in the Asia Pacific Consensus Report in 2016.

First of all, the response to neuromodulators is very mixed in the setting of refractory reflux, which involves patients who failed PPI therapy trials of 8 to 12 weeks and are still symptomatic, he said. “Tricyclics and selective serotonin reuptake inhibitors may have some efficacy and can be used as top-up therapy, but the value addition is small.”

Interestingly, Talley pointed to antireflux surgery providing a clinical benefit in reflux hypersensitivity. In a landmark USA trial evaluating antireflux surgery vs medical therapy vs no intervention in patients with refractory GERD, those with reflux hypersensitivity (documented on oesophageal pH monitoring) showed an excellent response to surgery (67 percent success) compared with a limited response to combination medical therapy (28 percent success). [N Engl J Med 2019;381:1512-1523; N Engl J Med 2019;381:1580-1582]

“However, surgery should only be considered in very carefully selected cases with severe refractory GERD symptoms who have definitely failed medical therapy,” Talley stressed.

Another approach to consider for refractory heartburn is diaphragmatic breathing, which was done in a very elegant study in Singapore, he said.

A small but important randomized trial showed that diaphragmatic breathing did improve reflux symptoms and belching. Talley pointed out that this might be related to an increased cruel diaphragmatic tone, although the exact mechanism remains uncertain. [Clin Gastroenterol Hepatol 2018;16:407-416]

When it comes to the management of severe heartburn and regurgitation, Talley suggested that clinicians carefully assess the patients whom they are giving PPI therapy to.

“If they're refractory, consider perhaps some additional therapies like alginate or even a H2 receptor antagonist trial for a short period and then … test patients more thoroughly to come up with their likely underlying problem and go from there in terms of management,” he added.