Optimal Wireless Reflux Monitoring Metrics to Predict Discontinuation of Proton Pump Inhibitor Therapy

Abstract

Introduction: Ambulatory reflux monitoring performed off proton pump inhibitor (PPI) is the gold standard diagnostic test for nonerosive gastroesophageal reflux disease (GERD). However, the diagnostic metrics and optimal duration of monitoring are not well defined. This study evaluated the performance of multiple metrics across distinct durations of wireless reflux monitoring off PPI against the ability to discontinue PPI therapy in patients with suboptimal PPI response.

Methods: This single-arm clinical trial performed over 4 years at 2 centers enrolled adults with troublesome GERD symptoms and inadequate response to > 8 weeks of PPI. Participants underwent 96-hour wireless pH monitoring off PPI. Primary outcome was whether the subject successfully discontinued PPI or resumed PPI within 3 weeks.

Results: Of 132 participants, 30% discontinued PPI. Among multiple metrics assessed, total acid exposure time (AET) of 4.0% performed best in predicting PPI discontinuation (odds ratio 2.9 [95% confidence interval 1.4, 6.4]; P = 0.006), with other thresholds of AET and DeMeester score performing comparably. AET was significantly higher on day 1 of monitoring compared with other days, and prognostic performance significantly declined when only assessing the first 48 hours of monitoring (area under the curve for 96 hours 0.63 vs area under the curve for 48 hours 0.57; P = 0.01).

Discussion: This clinical trial highlights the AET threshold of 4.0% as a high-performing prognostic marker of PPI discontinuation. 96 hours of monitoring performed better than 48 hours, in predicting ability to discontinue PPI. These data can inform current diagnostic approaches for patients with GERD symptoms who are unresponsive to PPI therapy.

Trial registration: ClinicalTrials.gov NCT03202537.

Figure 1.. Flow chart of study enrollment.

Parenthesis indicate site (patients from Northwestern University/patients from Washington University).

Figure 2.. Receiver operating characteristics for an acid exposure time threshold of 4.0% in predicting ability to discontinue PPI for four different durations of reflux monitoring off PPI.

Area under the curve (AUC) for 96 hours of monitoring is significantly greater than that of 24 hours (p=0.03) and that of 48 hours (p=0.10). AUC is similar for 24 hours (day 1) and 48 hours (days 1 and 2) of monitoring (p=0.49). AUC is similar for 96 hours total and 96 hours excluding day 1 (days 2, 3, and 4) of monitoring (p=0.43).

Figure 3.

Forest plot comparing risk estimates for predicting ability to discontinue PPI between 96-hour, 48-hour, and 96-hour with day 1 excluded monitoring