- Email: [email protected]
W1117 Influence of CYP2C19 Polymorphism on Lansoprazole and Rabeprazole Maintenance Treatment of Reflux Esophagitis
AGA Abstracts
W1116 W1118
Evidence That PPI Withdrawal May Exacerbate Symptoms and Increase Esophageal Acid Exposure in Patients With Gastroesophageal Reflux Disease Fernando Fornari, Renato B. Fagundes, Helena A. Goldani, Taira P. Liell, José C. Tomiozzo, Sergio G. Barros
Omeprazole Magnesium 20.6mg is an Effective Therapy for Frequent Nocturnal Heartburn in Medically Unsupervised Subjects With Frequent Heartburn Geetha N. Erasala, Roger D. Gibb, David Ramsey, Lisa Galletta, John McRorie
Background: A recent study has shown that proton pump inhibitor (PPI) therapy induces acid-related symptoms in healthy volunteers after PPI withdrawal. Rebound acid hypersecretion (RAHS) is believed to arise from the trophic effects of the PPI-induced hypergastrinemia on the oxyntic mucosa, lasting 4-8 weeks after discontinuing the PPI therapy. Aims: To assess whether PPI withdrawal may exacerbate reflux symptoms and increase esophageal acid exposure in patients with gastroesophageal reflux disease (GERD). Methods: Patients consecutively investigated for GERD with a validated symptoms questionnaire and 24h pH monitoring off PPI had their data revised from a prospectively constructed database. Heartburn and regurgitation in the last week before pH monitoring were scored between 0 (no symptom) and 5 (worst). GERD was defined according to Montreal criteria. Patients were classified as “naïve to PPI therapy” (group 1) or “studied after discontinuing regular use of PPI”, which were reclassified according to the interval in days between PPI withdrawal and pH monitoring: 7-10 (group 2), 11-20 (group 3), and 21-90 (group 4). Results: Among 329 patients investigated for GERD (age 47 ± 15 years, 64% women, BMI 26 ± 3.8 kg/m2), those who discontinued PPI either between 7-10 days or 11-20 days scored higher for symptoms than groups 1 (naïve to PPI, P < 0.001) and 4 (21-90 days, P < 0.05). Acid exposure was higher only in patients who discontinued PPI between 11-20 days, in comparison with groups 1 (naïve do PPI, P < 0.05) and 4 (21-90 days, P < 0.01). When analyzing GERD patients (n = 249, figure), those who discontinued PPI between 7-10 days scored higher for symptoms compared to groups 1 and 4, whereas acid exposure was higher only in patients evaluated after 11-20 days of PPI withdrawal. Conclusions: This study suggests that PPI withdrawal may exacerbate reflux symptoms and increase acid exposure in patients with GERD. Symptoms were more remarkable soon after (7-10 days) discontinuation of PPI, whereas increased acid reflux had a later peak at 11-20 days, followed by attenuation of both symptoms and acid exposure. Whether these findings are related with a sequence of events starting with RAHS and ending with a protective response of the esophagus needs to be addressed.
Background: An AGA-sponsored Gallup poll showed heartburn frequently occurs at night among individuals with reflux symptoms: 79% reported nocturnal heartburn and 71% used OTC medications to treat their symptoms1. The aim of this study was to assess the efficacy of omeprazole magnesium 20.6mg, switched Rx to OTC in 2003, for treatment of frequent heartburn when dosed one pill a day prior to breakfast. Studies of OTC omeprazole magnesium demonstrated day-long (i.e., 24 hours) relief of frequent heartburn during a 14-day treatment course. Methods: Two randomized, double-blind, placebo-controlled, multicenter clinical studies were conducted in medically unsupervised subjects with frequent heartburn (2 or more days/wk; n=2,086). A post-hoc analysis of the subset of subjects reporting frequent nocturnal heartburn (2 or more nights/wk; n=1,114) was assessed for percent nights with no nocturnal heartburn over the 14-day treatment period. Results: Fifty-four percent of subjects experienced frequent heartburn at night during the run in period. After the first dose and over the 14-day treatment period, omeprazole magnesium 20.6mg was more effective than placebo for nocturnal heartburn relief (p<0.032). Conclusions: Omeprazole magnesium 20.6mg is effective therapy for nocturnal heartburn among medically unsupervised individuals with frequent heartburn, both after the initial dose and over a 14-day regimen. There was a >3-fold increase in the percent of subjects with zero nocturnal heartburn with the omeprazole 14-day regimen versus placebo.
W1117 Influence of CYP2C19 Polymorphism on Lansoprazole and Rabeprazole Maintenance Treatment of Reflux Esophagitis Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa Background: Reflux esophagitis (RE) sometimes recurs despite ongoing maintenance proton pump inhibitor (PPI) treatment. Lansoprazole (LPZ) is metabolized by CYP2C19, and the acid suppressive effects of LPZ are influenced by the CYP2C19 polymorphism. In contrast, due to the different metabolic pathways, the suppressive effects of rabeprazole (RPZ) on gastric acid secretion are less affected by CYP2C19 polymorphism. It has been confirmed that the Japanese population has a greater variation in distribution of the CYP2C19 genotype than that in Western countries. This study aimed to endoscopically evaluate the RE relapse rates during PPI (LPZ or RPZ) maintenance treatment for each CYP2C19 genotype in Japanese patients. Methods: One hundred and thirteen patients (average age, 61.9 years; male/female, 59/54) with initial healing of RE by 8 weeks of PPI therapy were enrolled. As maintenance therapy, patients were treated with LPZ 15 mg/day (the first 82 consecutive patients) or RPZ 10 mg/day (the next consecutive 31 patients) for 6 months. The CYP2C19 genotype was assessed before the treatment. Patients were endoscopically investigated for relapse at 6 months. Results: No significant differences were seen in background factors between CYP2C19 genotypes, or between LPZ and RPZ groups. The overall relapse rate in the LPZ group was 23.2%, and the relapse rate for each CYP2C19 genotype was 38.5% for homoEM, 22.0% for heterozygous-EM hetero-EM, and 0% for PM, with significant differences seen between groups. The overall relapse rate in the RPZ group was 3.2% (1/31), and no statistical differences seen between CYP2C19 genotypes. The overall relapse rate was significantly higher in the LPZ group than it in the RPZ group. Conclusions: Administration of RPZ (10 mg/day) demonstrated much lower recurrence rate during RE maintenance therapy, and the efficacy may be uninfluenced by the CYP2C19 polymorphism.
W1119 Rikkunshito Improves PPI-Refractory NERD: A Prospective Randomized MultiCenter Trial in Japan Kazunari Tominaga, Yasuhiro Fujiwara, Yasuyuki Shimoyama, Eiji Umegaki, Ryuichi Iwakiri, Kazuhide Higuchi, Motoyasu Kusano, Kazuma Fujimoto, Tetsuo Arakawa, Study Group the GERD 4 Background & Aim: Proton pump inhibitors (PPIs) cannot completely relieve the symptoms of patients with non-erosive gastroesophageal reflux disease (NERD) even if double the standard dose is administered. Therefore, additional therapeutic modalities for refractory NERD patients to PPIs are required. We conducted a study in Japanese refractory NERD patients to compare efficacy in relieving symptoms of a traditional Japanese medicine, rikkunshito, in combination with a standard dose of rabeprazole (RPZ) with a double dose regimen of RPZ by a prospective randomized multi-center trial. Methods: Refractory NERD is defined as a score of more than 8 points estimated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), for five questions on acid reflux-related symptoms, and seven questions on dyspeptic (dysmotility) symptoms, after 4 weeks treatment with RPZ (10 mg). In this multi-center trial, 65 patients with refractory NERD were randomly assigned to 4 weeks of either combination therapy (n=30, mean age 64.2, M/F=12/18): rikkunshito (7.5 g/day, three times) with RPZ (10 mg) once daily or a double dose of RPZ (n=35, mean age 63.9, M/F=12/23). Severity of gastrointestinal symptoms was assessed using FSSG after treatment commencement. The primary endpoint was change in the FSSG score, and therapeutic improvement was defined as patients with a 50% decrease from the previous
S-655
AGA Abstracts
W1116 W1118
Evidence That PPI Withdrawal May Exacerbate Symptoms and Increase Esophageal Acid Exposure in Patients With Gastroesophageal Reflux Disease Fernando Fornari, Renato B. Fagundes, Helena A. Goldani, Taira P. Liell, José C. Tomiozzo, Sergio G. Barros
Omeprazole Magnesium 20.6mg is an Effective Therapy for Frequent Nocturnal Heartburn in Medically Unsupervised Subjects With Frequent Heartburn Geetha N. Erasala, Roger D. Gibb, David Ramsey, Lisa Galletta, John McRorie
Background: A recent study has shown that proton pump inhibitor (PPI) therapy induces acid-related symptoms in healthy volunteers after PPI withdrawal. Rebound acid hypersecretion (RAHS) is believed to arise from the trophic effects of the PPI-induced hypergastrinemia on the oxyntic mucosa, lasting 4-8 weeks after discontinuing the PPI therapy. Aims: To assess whether PPI withdrawal may exacerbate reflux symptoms and increase esophageal acid exposure in patients with gastroesophageal reflux disease (GERD). Methods: Patients consecutively investigated for GERD with a validated symptoms questionnaire and 24h pH monitoring off PPI had their data revised from a prospectively constructed database. Heartburn and regurgitation in the last week before pH monitoring were scored between 0 (no symptom) and 5 (worst). GERD was defined according to Montreal criteria. Patients were classified as “naïve to PPI therapy” (group 1) or “studied after discontinuing regular use of PPI”, which were reclassified according to the interval in days between PPI withdrawal and pH monitoring: 7-10 (group 2), 11-20 (group 3), and 21-90 (group 4). Results: Among 329 patients investigated for GERD (age 47 ± 15 years, 64% women, BMI 26 ± 3.8 kg/m2), those who discontinued PPI either between 7-10 days or 11-20 days scored higher for symptoms than groups 1 (naïve to PPI, P < 0.001) and 4 (21-90 days, P < 0.05). Acid exposure was higher only in patients who discontinued PPI between 11-20 days, in comparison with groups 1 (naïve do PPI, P < 0.05) and 4 (21-90 days, P < 0.01). When analyzing GERD patients (n = 249, figure), those who discontinued PPI between 7-10 days scored higher for symptoms compared to groups 1 and 4, whereas acid exposure was higher only in patients evaluated after 11-20 days of PPI withdrawal. Conclusions: This study suggests that PPI withdrawal may exacerbate reflux symptoms and increase acid exposure in patients with GERD. Symptoms were more remarkable soon after (7-10 days) discontinuation of PPI, whereas increased acid reflux had a later peak at 11-20 days, followed by attenuation of both symptoms and acid exposure. Whether these findings are related with a sequence of events starting with RAHS and ending with a protective response of the esophagus needs to be addressed.
Background: An AGA-sponsored Gallup poll showed heartburn frequently occurs at night among individuals with reflux symptoms: 79% reported nocturnal heartburn and 71% used OTC medications to treat their symptoms1. The aim of this study was to assess the efficacy of omeprazole magnesium 20.6mg, switched Rx to OTC in 2003, for treatment of frequent heartburn when dosed one pill a day prior to breakfast. Studies of OTC omeprazole magnesium demonstrated day-long (i.e., 24 hours) relief of frequent heartburn during a 14-day treatment course. Methods: Two randomized, double-blind, placebo-controlled, multicenter clinical studies were conducted in medically unsupervised subjects with frequent heartburn (2 or more days/wk; n=2,086). A post-hoc analysis of the subset of subjects reporting frequent nocturnal heartburn (2 or more nights/wk; n=1,114) was assessed for percent nights with no nocturnal heartburn over the 14-day treatment period. Results: Fifty-four percent of subjects experienced frequent heartburn at night during the run in period. After the first dose and over the 14-day treatment period, omeprazole magnesium 20.6mg was more effective than placebo for nocturnal heartburn relief (p<0.032). Conclusions: Omeprazole magnesium 20.6mg is effective therapy for nocturnal heartburn among medically unsupervised individuals with frequent heartburn, both after the initial dose and over a 14-day regimen. There was a >3-fold increase in the percent of subjects with zero nocturnal heartburn with the omeprazole 14-day regimen versus placebo.
W1117 Influence of CYP2C19 Polymorphism on Lansoprazole and Rabeprazole Maintenance Treatment of Reflux Esophagitis Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Tooru Shimosegawa Background: Reflux esophagitis (RE) sometimes recurs despite ongoing maintenance proton pump inhibitor (PPI) treatment. Lansoprazole (LPZ) is metabolized by CYP2C19, and the acid suppressive effects of LPZ are influenced by the CYP2C19 polymorphism. In contrast, due to the different metabolic pathways, the suppressive effects of rabeprazole (RPZ) on gastric acid secretion are less affected by CYP2C19 polymorphism. It has been confirmed that the Japanese population has a greater variation in distribution of the CYP2C19 genotype than that in Western countries. This study aimed to endoscopically evaluate the RE relapse rates during PPI (LPZ or RPZ) maintenance treatment for each CYP2C19 genotype in Japanese patients. Methods: One hundred and thirteen patients (average age, 61.9 years; male/female, 59/54) with initial healing of RE by 8 weeks of PPI therapy were enrolled. As maintenance therapy, patients were treated with LPZ 15 mg/day (the first 82 consecutive patients) or RPZ 10 mg/day (the next consecutive 31 patients) for 6 months. The CYP2C19 genotype was assessed before the treatment. Patients were endoscopically investigated for relapse at 6 months. Results: No significant differences were seen in background factors between CYP2C19 genotypes, or between LPZ and RPZ groups. The overall relapse rate in the LPZ group was 23.2%, and the relapse rate for each CYP2C19 genotype was 38.5% for homoEM, 22.0% for heterozygous-EM hetero-EM, and 0% for PM, with significant differences seen between groups. The overall relapse rate in the RPZ group was 3.2% (1/31), and no statistical differences seen between CYP2C19 genotypes. The overall relapse rate was significantly higher in the LPZ group than it in the RPZ group. Conclusions: Administration of RPZ (10 mg/day) demonstrated much lower recurrence rate during RE maintenance therapy, and the efficacy may be uninfluenced by the CYP2C19 polymorphism.
W1119 Rikkunshito Improves PPI-Refractory NERD: A Prospective Randomized MultiCenter Trial in Japan Kazunari Tominaga, Yasuhiro Fujiwara, Yasuyuki Shimoyama, Eiji Umegaki, Ryuichi Iwakiri, Kazuhide Higuchi, Motoyasu Kusano, Kazuma Fujimoto, Tetsuo Arakawa, Study Group the GERD 4 Background & Aim: Proton pump inhibitors (PPIs) cannot completely relieve the symptoms of patients with non-erosive gastroesophageal reflux disease (NERD) even if double the standard dose is administered. Therefore, additional therapeutic modalities for refractory NERD patients to PPIs are required. We conducted a study in Japanese refractory NERD patients to compare efficacy in relieving symptoms of a traditional Japanese medicine, rikkunshito, in combination with a standard dose of rabeprazole (RPZ) with a double dose regimen of RPZ by a prospective randomized multi-center trial. Methods: Refractory NERD is defined as a score of more than 8 points estimated using the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG), for five questions on acid reflux-related symptoms, and seven questions on dyspeptic (dysmotility) symptoms, after 4 weeks treatment with RPZ (10 mg). In this multi-center trial, 65 patients with refractory NERD were randomly assigned to 4 weeks of either combination therapy (n=30, mean age 64.2, M/F=12/18): rikkunshito (7.5 g/day, three times) with RPZ (10 mg) once daily or a double dose of RPZ (n=35, mean age 63.9, M/F=12/23). Severity of gastrointestinal symptoms was assessed using FSSG after treatment commencement. The primary endpoint was change in the FSSG score, and therapeutic improvement was defined as patients with a 50% decrease from the previous
S-655
AGA Abstracts