Sean Delshad, MD, MBA, on PPI-Refractory GERD

In this podcast, Sean Delshad, MD, MBA, discusses the true extent of gastroesophageal reflux disease in the United States, the proportion of patients with GERD that is refractory to proton pump inhibitors, and prospects for new treatments of this common disease. 

References: 

• Delshad SD, Almario C2, Chey WD, et al. Prevalence of gastroesophageal reflux disease and proton pump inhibitor-refractory symptoms. Gastroenterology. 2020;158(5):1250-1261. https://doi.org/10.1053/j.gastro.2019.12.014
• Moayyedi P, Eikelboom JW, Bosch J, et al; COMPASS Investigators. Safety of proton pump inhibitors based on a large, multiyear, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157(3):682-691. https://doi.org/10.1053/j.gastro.2019.05.056
• Vaezi MF, Fass R, Vakil N et al. IW-3718 reduces heartburn severity in patients with refractory gastroesophageal reflux disease in a randomized trial. Published online February 21, 2020. Gastroenterology. https://doi.org/10.1053/j.gastro.2020.02.031
• Lee JK, Merchant SA, Schneider JL et al. Proton pump inhibitor use and the risk of colorectal, liver, and pancreatic cancers in a community-based population. Am J Gastroenterol. 2020;115(5):706-715. doi: 10.14309/ajg.0000000000000591

Sean Delshad, MD, MBA, is a clinical researcher from the Cedars-Sinai Center for Outcomes Research and Education and faculty member of the David Geffen School of Medicine at UCLA in Los Angeles, California.

TRANSCRIPT:

Rebecca Mashaw: Hello, and welcome to another installment of Podcasts360, your go‑to resource for medical news and clinical updates. I'm your moderator, Rebecca Mashaw with Consultant360 Specialty Network.

With us today is Dr Sean Delshad, clinical researcher from the Cedars Sinai Center for Outcomes Research and Education and a faculty member of the David Geffen School of Medicine at UCLA.

Dr Delshad will discuss the recently published report on the National Gastrointestinal Survey that he and his colleagues conducted to gather data on the prevalence of gastroesophageal reflux disease in the United States and to determine what proportion of patients with GERD show proton-pump-inhibitor-refractory symptoms.

Thank you for joining us today, Dr Delshad. You and your colleagues found that about 44% of the almost 71,000 participants in your study reported having had GERD symptoms in the past. Almost 31%—more than 23,000—said they'd had symptoms in the past week. How do these results compare with those of previous estimates of the prevalence of GERD in the United States?

Sean Delshad: Previous estimates of GERD in the United States ranged from 18% to 28%, with a weighted average of 20%. These prevalence rates were based on samples that are no longer representative of the US. That was a main reason we conducted our study to update our understanding of the prevalence and epidemiology of GERD.

In 2015, we performed the national GI survey, population‑based, out of GI symptoms and over 71,000 Americans. The survey was administered via an online mobile application. We were able to recruit a representative sample of the US by enacting quotas for certain demographics, such as age and sex, and matching it to the latest US Census data.

We found that 31% of our survey respondents had experienced symptoms in the past week. It's hard to make direct comparisons between our study and the various prior studies in the past because of different definitions and different populations. Our study does seem to imply that the prevalence of GERD is increasing.

Rebecca Mashaw: You also found that more than 54% of participants taking proton-pump inhibitors daily to treat GERD still reported symptoms. Based on these findings, which populations were most likely to experience treatment refractory GERD? Which patient demographics or characteristics played the largest role?

Sean Delshad: We looked at various predictors of GERD and PPI-refractory GERD. We specifically looked at age, gender, race, ethnicity, education level, marital status, income, and various comorbidities.

We found 5 groups that had increased odds of having PPI-refractory GERD: those who are younger, those who are women, those of Latino race or ethnicity, those with irritable bowel syndrome or IBS, and those with Crohn's disease.

From our study, it's not clear which characteristics play the largest role. That said, the highest odds ratio we found was in those with Crohn's disease. Those respondents had a 5‑time odds of having PPI-refractory GERD as compared to those without the disease.

Rebecca Mashaw: Your conclusions recommend further research and development of new therapies for GERD. What promising medications are under study now? What role do nutritional therapies, for example, play in the treatment regimen for PPI-refractory GERD?

Sean Delshad: Well, lifestyle modification should always be a part of the treatment plan for GERD and PPI-refractory GERD. We generally recommend avoiding known dietary triggers such as alcohol, caffeine, carbonated beverages, and spicy foods.

There's really limited evidence for avoiding these foods. The lifestyle modifications that are backed by the evidence include weight loss and elevating the head of the bed, for those who have nighttime symptoms.

There are new therapies that are showing promise for GERD. One is the new class of potassium‑competitive acid blockers. The most common and studied being vonoprazan. It works by preventing potassium from binding the gastric hydrogen potassium, ATPA. It's supposed to lead to a more sustained decrease in stomach acidity.

Other new therapies are targeting causes of GERD, other than gastric acid—A lot of PPI-refractory GERD symptoms may in fact be due to reflex of bile. Ironwood Pharmaceuticals, who I should mention funded our study, has created an extended-release gastric‑retained bile acid sequestrant, colesevelam, that is showing promise as well.

Michael Vaize and his colleagues just published a randomized trial that demonstrated significantly reduced heartburn symptoms when adding colesevelam to a traditional PPI for those experiencing refractory symptom.

Rebecca Mashaw: There have also been controversies about the long‑term use of PPIs, in particularly about the potential for adverse effects associated with long‑term use. What is your opinion on the relative risks and benefits of PPIs for patients who do find them effective in treating GERD?

Sean Delshad: We generally try to use PPIs at the lowest dose necessary for the shortest duration. Unfortunately, many of our patients do end up being on PPIs for a long time. There's been a lot of recent evidence suggesting that the prolonged use of PPIs is not associated with a lot of adverse events.

For example, data from a large randomized trial that was published in Gastroenterology September of 2019, demonstrated that patients who were on a PPI for 3 years had no increased rates of adverse events as compared to those who are not on a PPI.

There was one increased adverse event, that was C diff. But other than that, they didn't find anything. An even more recent study accepted to the Red Journal, just recently, they showed that those who are on PPIs for at least 2 years were not found to have an increased risk of various GI cancers that they looked at.

So, if patient finds PPI therapy beneficial, I would say the chances are the risk‑benefit ratio is in favor of continuing the therapy as necessary.

Rebecca Mashaw: What would you say are the key takeaways from your research for gastroenterologists who are treating patients with PPI-refractory GERD?

Sean Delshad: The main takeaway from our research is that PPI refractory GERD is very common. Fifty-four percent of the survey respondents had PPI-refractory GERD symptoms. That's huge. I think that big-picture takeaway here is that GERD is more than just gastric acids.

We need to think of other causes, such as functional GERD and bile acid reflux, and spend more energy researching and developing novel therapies starting with other causes.

Rebecca Mashaw: Thank you for sharing your insights with us today, Dr Delshad.

Sean Delshad: Just wanted to thank my mentors and coauthors on the study, Dr Christopher Almario and Dr Brennan Spiegel at Cedars Sinai.