Abnormal pH results were similar in patients with gastroesophageal reflux disease (GERD) who improved or failed to improve on a once-daily dose of a proton pump inhibitor (PPI), but 75% of patients who failed treatment demonstrated either functional heartburn or reflux hypersensitivity, based on data from 29 adults.
Previous research on PPI failure in GERD patients has focused on twice-daily doses; “the purpose of the study was to compare impedance-pH parameters between patients who failed versus those who responded to PPI once daily,” wrote Jason Abdallah, MD, of Case Western Reserve University in Cleveland and colleagues.
In a study published in, the investigators reviewed data from adults diagnosed with GERD who were treated with PPI therapy. The 16 who reported heartburn and/or regurgitation at least twice a week for 3 months while on a standard, once-daily PPI dose were classified as the failure group. The 13 patients who reported complete symptom resolution for at least 4 weeks while on the same standard dose were classified as the success group.
Most of the patients in the PPI-failure group (75%) were found to have either functional heartburn or reflux hypersensitivity with GERD. Impedance and pH parameters did not differ significantly between the PPI-failure and -success group, the researchers noted. Abnormal pH test results were similar between the groups, occurring in four of the patients who were successfully treated with PPI (31%) and four of the patients who failed PPI treatment (25%).
All patients completed the Short-Form 36 (SF-36) and GERD Health-Related Quality of Life (GERD-HRQL) questionnaires, and all underwent upper endoscopy and combined 24-hour esophageal impedance and pH monitoring within 2-4 weeks of study enrollment and while following their PPI treatment plans. There were no significant differences in demographic characteristics between the success and failure groups; the mean ages were 55 years and 47 years, respectively.
The patients in the success group averaged higher scores on the SF-36 than the failure group, but the difference was not significant. On the GERD-HRQL, treatment-failure patients reported that overall heartburn and either heartburn or bloating while lying down were the symptoms they found most annoying on a daily basis.
Among the treatment-failure patients, 10 (62%) had normal acid exposure and negative symptom-reflux association, 2 patients (13%) had normal acid exposure and positive symptom-reflux association, and 4 patients (25%) had abnormal esophageal acid exposure. Patients in the treatment failure group reported a total of 315 episodes of either heartburn or regurgitation.
Endoscopy findings were normal in most of the patients in both groups; 81% of the treatment-failure patients and 69% of the treatment-success patients had normal upper endoscopy findings. Abnormal findings in the treatment-success group included one case of erosive esophagitis, two cases of Barrett’s esophagus, three cases of nonobstructive Schatzki rings, and five cases of hiatal hernia. Abnormal findings in the treatment-failure group included two cases of Schatzki rings, one case of esophageal stricture, and three cases of hiatal hernia.
The total number of reflux events was similar between the groups; 1,279 in the treatment-failure group and 1,099 in the treatment-success group, with the number of reflux events per patient averaging 80 and 84, respectively.
“Our results support the hypothesis that PPI failure is primarily driven by esophageal hypersensitivity,” the researchers noted. The similarity in impedance and reflux “implies that the shift to nonacidic reflux is a general PPI phenomenon, as opposed to being unique to PPI-failure patients,” they said.
The study was limited by the small patient population, but the results provide some insight into refractory GERD and suggest that patients who fail to respond to once-daily PPI might benefit from a neuromodulator, as well as psychological interventions including cognitive-behavioral therapy, hypnotherapy, relaxation techniques, mindfulness, and biofeedback, the researchers concluded.
Dr. Abdullah had no financial conflicts to disclose; a coauthor disclosed relationships with companies including Ironwood Pharmaceuticals, Mederi Therapeutics, and Ethicon Pharmaceuticals.
SOURCE: Abdallah J et al. Clin Gastroenterol Hepatol. 2018;