Causes of failure of antacids (PPIs) with reflux esophagitis (Part 2)

Posted by Doctor Mai Vien Phuong - Department of Examination & Internal Medicine, Vinmec Central Park International General Hospital

Patients who continue to have symptoms despite PPI therapy are considered to have refractory GERD, usually defined as the persistence of typical symptoms unresponsive to stable, twice-daily doses of PPIs. every day for at least 12 weeks of treatment. Up to 30% of GERD patients have treatment-resistant GERD.

Causes of failure of antacids (PPIs) with reflux esophagitis include:

Prior to further evaluation, all patients with suspected PPI failure should be evaluated for adherence. Poor compliance is probably the most common cause of reported PPI failure.
Several factors can contribute to patient compliance when prescriptions are long-term prescribed. These factors include knowledge of the disorder being treated and the type of medication prescribed, severity of symptoms, side effects, amount of medication or supplements, age and personality of the patient. patients (see Table 2). In addition, GERD is primarily a symptom-driven disease in which many patients continue to take medication as long as they have symptoms. When symptoms subside, patients often no longer want to use PPIs, leading to discontinuation of treatment. According to a large population-based survey, only 55% of GERD patients took a PPI once daily for the 4 weeks prescribed. In contrast, 37% took their PPIs for 12 days or less during the month.
Table 2. Factors that may adversely affect patient adherence to PPI:

While patients can adhere to once-daily PPI therapy, many may not be taking their medication properly. This is particularly relevant for PPIs, as timing and frequency of dosing are critical to achieving maximum effectiveness. PPIs should be taken about half an hour before meals. This is supported by a study that demonstrated significantly better control of stomach acid when omeprazole or lansoprazole was taken 15 minutes before breakfast, compared with no breakfast. Unfortunately, many patients are not aware of the need to take PPIs before meals, often because the doctor has not given proper instructions. Some patients may take PPIs at bedtime, again reducing the effectiveness of the drug by not taking it before meals.
An important clue for poor adherence is the recurrence of GERD-related symptoms after a period of definitive treatment of symptoms. Unlike the case of H 2 β-blockers, resistance to PPIs has not been documented.

It has been shown that Helicobacter pylori infection improves the effectiveness of acid suppression by PPIs. Studies have shown that the efficacy of PPIs in acid suppression is increased in H. pylori-positive patients when compared with non-H. pylori-infected patients. The proposed underlying mechanism is the migration of H. pylori closer to the corpuscle responsible for acid production during PPI treatment. These areas of the stomach contain parietal cells, which are responsible for acid production. However, long-term treatment with PPIs in patients with H. pylori infection can lead to atrophic gastritis, which can progress to intestinal metaplasia and dysplasia.
Holtmann et al demonstrated that among all patients with erosive esophagitis who received pantoprazole 40 mg once daily for 4 weeks, 23.7% of H. pylori infected patients did not cure their esophagitis. when compared with 13.4% of H. pylori-positive patients (P = 0.0005). Reduction of GERD symptoms was also significantly (P < 0.05) higher in H. pylori-positive patients (84%) when compared with H. pylori-negative patients (78%). However, the prevalence of H. pylori infection is decreasing rapidly in the United States and other developed countries resulting in a very low prevalence, inexplicably large proportion of patients with PPI failure.

Oral bioavailability may differ significantly from one PPI to another and may be further reduced when the drug is taken with food or an antacid. Bioavailability has been suggested as a contributing mechanism to PPI failure. For example, the bioavailability of omeprazole is about 30-40%, which is significantly lower than the 80% bioavailability of lansoprazole or pantoprazole. However, these pharmacokinetic properties appear to be clinically limited. With some minor differences, all PPIs have been shown repeatedly to have equivalent clinical efficacy.

A single summary was published in 1995 investigating the possible role of specific mutations in H+/K+ ‐ATPase that may lead to PPI resistance. Such contributing mutations were not found; however, no further studies on specific genetic mutations that cause PPI resistance are available in the literature.

Invite readers to refer to the following sections:
Causes of failure of antacids (PPIs) with reflux esophagitis (Part 1) Causes of failure of antacids (PPIs) with inflammatory bowel disease Reflux esophagitis (Part 2) Causes of failure of antacids (PPIs) with reflux esophagitis (Part 3) Causes of failure of antacids (PPIs) with reflux esophagitis (Part 3) Part 4)