Inadequate Acid Suppression—a Barrier to Healing Erosive Esophagitis

A discussion with leading physicians, Dr Joan Chen, assistant professor of gastroenterology and internal medicine at the University of Michigan Health, and Dr Prateek Sharma, professor of gastroenterology at the University of Kansas School of Medicine, about erosive esophagitis treatment challenges and how acid suppression affects long-term maintenance of healing.

TRANSCRIPT:

Announcer:  This program is sponsored by Phathom Pharmaceuticals, and is intended for healthcare professionals in the United States.

Joan Chen:  Approximately 20 to 30% of patients with severe grades of erosive esophagitis fail to heal on standard PPI therapy. Why might current treatments not work for some of our patients? Hello, and welcome to "Fireside Chats," a pocket series on acid-related disorders in clinical practice.

I'm your host, Dr. Joan Chen, assistant professor of gastroenterology and internal medicine at the University of Michigan Health. I'm here today with my colleague, Dr. Prateek Sharma, professor of gastroenterology at the University of Kansas, School of Medicine. Welcome, Prateek.

Dr. Prateek Sharma:  Thanks, Joan, for having me here today.

Dr. Chen:  I'm so happy you can join me. The issue at hand for today is that not all patients with erosive esophagitis will heal with currently available treatment. This can be frustrating for our physicians, and a burden to our patients.

Dr. Sharma:  That's a great observation, Joan. What we typically see is that among all grades of erosive esophagitis, 4-15% percent of patients will fail to achieve complete esophageal healing after 8 weeks of initial standard dose PPI therapy.

Also, what is clear and known is that patients with more severe disease have the highest failure rates. With one study, for example, showing that patients with the most severe form of erosive esophagitis, which is the Los Angeles or the LA grade D erosive esophagitis, can experience failure rates of approximately 30%.

Dr. Chen:  Wow. That's a high percentage of patients who will continue to have insufficiently-healed erosions even with PPI treatment.

Relapse does occur during the first 6 months of maintenance therapy for some patients, with reported relapse rates of 15 to 23% with mild esophagitis, or LA grades A or B, and 24 to 41% with moderate to severe esophagitis, or LA grades C or D. These issues can be challenging to manage in the clinic.

Dr. Sharma:  That's correct, Joan. This is a real problem. Patients with uncontrolled erosive esophagitis have the potential to experience serious complications, such as esophageal ulcer or esophageal stricture. We also know that reflux disease is the precursor for Barrett's esophagus, and is related to esophageal adenocarcinoma as well.

Dr. Chen:  We know that there are multiple reasons why currently available treatments may fail, including poor adherence to treatment or comorbidities. Another component, which sometimes we lose sight of is the extent to which acid needs to be suppressed to effectively heal erosions, correct?

Dr. Sharma:  That's correct again, Joan. We know for a while that there is an established relationship between the extent of gastric suppression and its impact on esophageal mucosal healing.

Dr. Chen:  That makes sense. Considering that when the gastric pH is low, like below a pH of 4, esophageal tissue has a reduced ability to proliferate and heal itself, right?

Dr. Sharma:  That's absolutely right. Studies have shown that there is a strong correlation between esophageal healing at 8 weeks, and the duration of time that the pH in the stomach above 4 was maintained.

In short, what we want to ensure, that acid is sufficiently suppressed, such that the gastric pH is raised to a level that is compatible with the healing of esophageal mucosa.

Dr. Chen:  Achieving a sufficient level of acid suppression can be challenging with our current standard of care, meaning PPIs, as the percentage of days spent above a pH of 4 can vary from 42 to 71%, depending on which PPI you use.

Dr. Sharma:  That's right, Joan. Part of the reason PPIs struggle to sustain acid suppression or full day may have to do with the inherent pharmacokinetics of the PPIs. PPIs have short half-lives of around 1 to 2 hours, depending on the PPI.

Because of this, and the irreversible binding of PPIs to acid pumps, what happens is towards the end of the dosing period, their levels may fall below a threshold that can inhibit newly-synthesized or newly-activated acid pumps.

Dr. Chen:  I also like to point out that another pitfall of PPI treatment is that its efficacy might depend on how fast the patient metabolizes the medication, with rapid metabolizers being more likely to fail treatment.

Dr. Sharma:  Joan, that's also absolutely true. We know that PPIs require acid for activation. They should be taken about 30 minutes before a meal, so that acid is present in the stomach in order to activate the PPIs. Taking all of this into account, compliance is key.

If patients don't adhere to the dosing requirements of PPI, specifically, consistent daily doses taken before a meal, they will not be able to achieve maximum acid suppression.

Dr. Chen:  The bottom line is that we need to remember that currently available treatments may not provide adequate acid suppression for all patients, and that inadequate acid suppression contributes to inadequate esophageal healing. Given these issues, what can we do to help some of these patients who fail to heal?

Dr. Sharma:  Excellent question, Joan. It comes down to an awareness of how PPIs need to be taken, the limitations of current therapies, and knowing that you may need to increase the frequency to twice daily. Switching to a different PPI with the goal of achieving sufficient acid suppression, specifically in those patients with more severe erosive esophagitis.

Dr. Chen:  That's really good advice, Prateek. Thank you so much for being here today to talk about this important issue.

Dr. Sharma:  That's my pleasure. It was great being here, and a great discussion, Joan. Thank you for having me on.

Dr. Chen:  To our listeners. I hope that this podcast has been informative on the need for adequate acid suppression in the initial healing of erosive esophagitis. Thank you for joining us today on Fireside Chats. Be sure to check out our next podcast in the series, where we will discuss challenges related to the maintenance of healing for patients with erosive esophagitis.

Announcer:  The references for the information discussed today are available in the transcript, which can be accessed on the site where you've listened to the podcast.

 
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