Presentations in GERD: Activity of Novel Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator ADX10059 in GERD
The novel metabotropic glutamate receptor 5 negative allosteric modulator ADX10059 has been shown to reduce reflux and esophageal acid exposure in both healthy individuals and patients with GERD. Zerbib and colleagues presented results from a double-blind, placebo-controlled, multicenter trial evaluating the effects of single-agent ADX10059 on symptom control in patients with GERD. The study enrolled 103 patients with responses to prior PPIs. After undergoing a 2-week baseline PPI washout period, patients were randomly assigned to receive ADX10059 120 mg (50 patients) or placebo (53 patients) twice daily for 2 weeks. The mean age of enrolled patients was 52 years, mean body mass index (BMI) was 26.7 kg/m2, and 52% were male. ADX10059 was significantly superior to placebo in regard to the change in the mean number of GERD symptom-free days from baseline to Week 2 (0.46 to 2.5 vs 0.72 to 1.71; P=.045) and the change in the mean number of heartburn-free days (0.98 to 2.93 vs 1.28 to 2.11; P=.037). ADX10059 also appeared to reduce heartburn and regurgitation severity and the number of days with postprandial GERD. Compared to placebo, ADX10059 was also associated with greater reductions in antacid use (P=.017) and improvements in total Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI SYM) score (P=.048), PAGI SYM heartburn/ regurgitation subscale (P=.007), and sleep disturbance (P=.022). Patient-reported medication efficacy was also significantly greater with ADX10059 versus placebo (P=.047). The 3 most common adverse events included dizziness (16%), vertigo (12%), and upper abdominal pain (10%); 66% of adverse events were mild, and no severe adverse events were observed.
Association Between BMI and Acid Exposure in Patients With Extraesophageal Reflux Disease
Although an association between obesity and the development of GERD has been observed, the relationship between BMI and esophageal acid exposure in patients with extraesophageal reflux disease has not been defined. To investigate this issue, Aslam and colleagues conducted a 48-hour off-treatment pH monitoring study of 365 patients with extraesophageal symptoms (80%) or typical GERD (20%). The median age of enrolled patients was 53 years; 73% were female; and the median BMI was 28 kg/m2 (interquartile ratio, 24-32 kg/m2). The investigators found a significant association between increasing BMI and greater esophageal acid exposure (P=.004), whether BMI was evaluated as a continuous variable or as a categorical variable, with normal BMI defined as 19 to less than 25 kg/m2, overweight as 25 to less than 30 kg/m2, and obese as more than 30 kg/m2. The greatest increase in acid exposure was noted between BMI of 25-30 kg/m2. BMI had a minimal effect above 30 kg/m2. Overall, these findings suggest a significant, nonlinear relationship between BMI and acid exposure.
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