Combinations of abnormal pH-impedance metrics better predicted nonresponse to proton pump inhibitor therapy, as well as benefit of treatment escalation, than individual metrics in patients with gastroesophageal reflux disease (GERD) on twice-daily PPI.
The researchers found a higher proportion of nonresponders to PPI in a group of patients that had combinations of abnormal reflux burden, characterized as acid exposure time greater than 4%, more than 80 reflux episodes, and/or mean nocturnal baseline impedance (MNBI) less than 1,500 ohms, with 85% of these patients improving following initiation of invasive GERD management such as antireflux surgery or magnetic sphincter augmentation.
Not only does the combination of metrics offer more value in identifying responders to PPI than individual metrics, but the combination also offer greater value in “subsequently predicting response to escalation of antireflux management,” study authors C. Prakash Gyawali, MD, of Washington University, St. Louis, and colleagues wrote in Gastroenterology.
Currently in question is the applicability of thresholds for metrics from pH impedance monitoring for studies performed on PPI. According to Dr. Gyawali and colleagues, thresholds from the Lyon Consensus may be too high and likewise lack optimal sensitivity for detecting refractory acid burden in patients on PPI, while thresholds based on pH-metry alone, as reported in other publications, may also lack specificity.
To determine which metrics from “on PPI” pH impedance studies predict escalation therapy needs, the researchers analyzed deidentified pH impedance studies performed in healthy volunteers (n=66; median age, 37.5 years) and patients with GERD (n = 43; median age, 57.0 years); both groups were on twice-daily PPI. The investigators compared median values for pH impedance metrics between healthy volunteers and patients with proven GERD using validated measures.
Data were included from a total of three groups: tracings from European and North American healthy volunteers who received twice-daily PPI for 5-7 days; tracings from European patients with heartburn-predominant proven GERD with prior abnormal reflux monitoring off PPI who subsequently received twice-daily PPI; and tracings from a cohort of patients with regurgitation-predominant, proven GERD and prior abnormal reflux monitoring off PPI who subsequently received twice-daily PPI.
A improvement in heartburn of at least 50%, as recorded on 4-point Likert-type scales, defined PPI responders and improvements following antireflux surgery in the European comparison group. Additionally, an improvement of at least 50% on the GERD Health-Related Quality of Life scale also characterized PPI responders and improvements following magnetic sphincter augmentation in the North American comparison group.
There was no significant difference between PPI responders and nonresponders in terms of individual conventional and novel reflux metrics. The combinations of metrics associated with abnormal reflux burden and abnormal mucosal integrity (acid exposure time >4%, >80 reflux episodes, and MNBI <1,500 ohms) were observed in 32.6% of patients with heartburn and 40.5% of patients with regurgitation-predominant GERD, but no healthy volunteers. The combinations were also observed in 57.1% and 82.4% of nonresponders, respectively.
The authors defined a borderline category (acid exposure time, >0.5% but <4%; >40 but <80 reflux episodes), which accounted for 32.6% of patients with heartburn-predominant GERD and 50% of those regurgitation-predominant GERD. Nonresponse among these borderline cases was identified in 28.6% and 81%, respectively.
“Performance characteristics of the presence of abnormal reflux burden and/or abnormal mucosal integrity in predicting PPI nonresponse consisted of sensitivity, 0.50; specificity, 0.71; and AUC, 0.59 (P = .15),” the authors explained. “Performance characteristics of abnormal and borderline reflux burden categories together in predicting PPI nonresponse consisted of sensitivity, 0.86; specificity, 0.36; and AUC, 0.62 (P = .07).”
Limitations of this study included its retrospective nature, small sample sizes for the healthy volunteer and GERD populations, and the lack of data on relevant clinical information, including body mass index, dietary patterns, and PPI types and doses. Additionally, the findings may lack generalizability because of the inclusion of only patients with GERD who underwent surgical management.
Despite these limitations, the researchers wrote that the findings and identified “thresholds will be useful in planning prospective outcome studies to conclusively determine when to escalate antireflux therapy when GERD symptoms persist despite bid PPI therapy.”
The study researchers reported conflicts of interest with several pharmaceutical companies. No funding was reported for the study.
