Does a Response to Proton Pump Inhibitor Therapy Indicate GERD?

Just because a patient’s upper gastrointestinal symptoms are alleviated by proton pump inhibitors (PPIs) doesn’t necessarily mean that they have gastroesophageal reflux disease (GERD), according to the December issue of Clinical Gastroenterology and Hepatology.

The efficacy of PPI therapy often is tested to determine whether patients’ symptoms are acid-related and if they have GERD—a chronic digestive disease that occurs when stomach acid, or occasionally bile, flows back (refluxes) into the esophagus. The backwash of acid irritates the lining of your esophagus and causes GERD signs and symptoms. There has been debate, however, about whether response to PPI therapy accurately identifies GERD.

Peter Bytzer et al. evaluated the diagnostic accuracy of the PPI test, analyzing data from a large, multi-national trial (the DIAMOND study) that compared the ability of several different methods to identify GERD. The study included 308 patients with frequent upper-gastrointestinal symptoms such as heartburn, central chest pain, or regurgitation.

The subjects were first given placebo and evaluated by endoscopy, wireless esophageal pH-metry, and symptom association monitoring. Individuals with GERD (n = 197) were identified based on the presence of reflux esophagitis, esophageal pH levels below 4, or positive results from symptom association monitoring. All patients were then given esomeprazole (40 mg daily) for 2 weeks and symptoms were recorded daily.

A positive response to the PPI test was observed in 69% of patients who actually had GERD and in 51% of those who did not. The below figure shows the responses of the most bothersome symptoms in patients with and without GERD.

Responses of the most bothersome symptoms in the last 3 days of active treatment with PPIs among patients with and without GERD. Abd, abdominal; Regurg, regurgitation

The PPI test has been widely used clinically to assess whether upper-GI symptoms are acid-related. However, some studies reported that it has a low level of specificity, and its value as a diagnostic test is limited compared with pH monitoring and symptom association monitoring.

The DIAMOND study addressed this issue in a relevant study population of patients attending primary care for any upper-gastrointestinal symptom, rather than just patients with reflux disease. Bytzer et al. state that in this well-characterized population of primary care patients with frequent upper-gastrointestinal symptoms of any type, the PPI test had a limited ability to correctly identify those with GERD, diagnosed by state-of-the art tests.

In an editorial that accompanies the article, Sander Veldhuyzen van Zanten points out that whether a patient responds to a PPI treatment is still clinically the most relevant result, irrespective of the cause. In primary care, patients are usually treated without an endoscopic examination, and it might not matter whether a patient who is complaining of upper-gastrointestinal symptoms has GERD or dyspepsia—all that matters is whether the patient feels better.

van Zanten also reminds readers that the PPI test is poorly defined —it is important to consider whether the PPI is given once a day or twice a day, the duration of therapy, and how treatment response is defined.

More Information About GERD:

• The NIH Website on GERD
• The Mayo Clinic Website on GERD

Read the article online.
Bytzer P, Jones R, Vakil N, et al. Limited ability of the proton-pump inhibitor test to identify patients with gastroesophageal reflux disease. Clin Gastroenterol Hepatol 2012;10:1360−1366.

Read the accompanying editorial.
van Zanten SV. Diamond GERD diagnosis studies: clinical feelings are good, but are measurements using a ppi test better? Clin Gastroenterol Hepatol 2012;10:1367−1368.