PCAB Treatment: A New Weapon to Combat Erosive Esophagitis

This transcript has been edited for clarity.

Hello. My name is John Pandolfino, and I'm the Hans Popper Professor of Medicine at the Feinberg School of Medicine at Northwestern University. I'm also the division chief of gastroenterology and hepatology at Northwestern Medicine in Chicago.

Today we're going to be talking about erosive esophagitis. Erosive esophagitis is one of the most severe complications of gastroesophageal reflux disease (GERD). It occurs when the exposure of the caustic gastric juice overwhelms the defense mechanisms that we have to prevent reflux.

Typically, reflux is prevented by the antireflux barrier, which is made up of the crural diaphragm and the lower esophageal sphincter. Once that gastric juice gets up into the esophagus, it is typically cleared with peristalsis.

If you have intact peristalsis, the bolus is pushed right back into the stomach. It's also buffered by saliva — the delivery of the saliva from peristalsis.

There's also a defense mechanism at the tissue level where there are molecular-level tight junctions, a very strong mucosa that allows for the acid to not penetrate deeper into the layers of the esophagus (the mucosa and the submucosa). When that becomes excessive and it overwhelms those defense mechanisms, you get a breakdown in the mucosa. That's when esophagitis develops, which will lead to other complications, like ulceration, bleeding, and stricture.

The way we treat this is not at the root cause. We don't try to create an antireflux barrier unless we go through surgery. And we can't really improve the peristalsis and the salivation.

So we address the acidity, the causticity of the gastric juice. There are now two very effective medicines for this. One is the proton pump inhibitors (PPIs) and the other is the potassium-competitive acid blockers (PCABs).

There is a problem, though. The PPIs in and of themselves require a delicate interplay between mealtimes and the delivery of the medicine; you have to take the medicine 30-60 minutes before you have a meal.

The reason for that is that PPIs are prodrugs. They need to be absorbed and secreted back into the parietal cell, and they can only block the parietal cell when it's active. They are also irreversibly bound to that.

There are a lot of limitations with the PPIs. There are patients who have refractory esophagitis despite being on PPIs. We believe that most of this is not really related to being a hypermetabolizer, although there are some patients who hypermetabolize those medications. We feel that in most of these patients, it's due to that delivery; they're compliant but they don't get the timing right.

The way to circumvent that is with the PCABs. The PCABs get around this because they're acid-stable medications that are delivered in active form. They're able to bind both inactive and active proton pumps, circumventing all of these issues.

So if you have a patient who has a significant motility issue or really severe reflux, the PCABs are perfect. Where I found this most effective in my practice is in patients with scleroderma, achalasia after treatment, and gastroparesis. These are all patients who have defective clearance mechanisms or an inability to have accurate timing and synergy of the delivery of the medicine and the actual meal time.

We've had some very nice success with scleroderma patients who were previously refractory to PPI therapy where we were able to heal these patients. We were able to do this also with those with achalasia.

Last but not least, when you see patients who have really severe esophagitis, and they don't have scleroderma or are not post-achalasia, you have to consider that they may have gastroparesis. Those are also patients who are going to have problems with the absorption and timing of a PPI.

In this day and age, I think we have a new weapon to combat erosive esophagitis, especially very difficult refractory cases. PCABs are doing very nicely in our clinical practice and really fill a niche for our patients. Thank you very much for joining me today. I hope you learned something about erosive esophagitis and these new approaches.

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: Potassium-Competitive Acid Blockers (PCABs) Provide a New Weapon to Combat Erosive Esophagitis - Medscape - Apr 19, 2024.

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