Relief of Night-time Symptoms Associated With Gastroesophageal Reflux Disease Following 4 Weeks of Treatment With Pantoprazole Magnesium: The Mexican Gastroesophageal Reflux Disease Working Group.

BACKGROUND/AIMS: To evaluate the effectiveness of pantoprazole magnesium (pantoprazole-Mg) 40 mg in the relief of esophageal and extra-esophageal symptoms of gastroesophageal reflux disease (GERD), particularly night-time symptoms. METHODS: Patients (aged 18-50 years) with 3-month history of heartburn and/or acid regurgitation plus at least one other symptom in the last week were enrolled in a nationwide, prospective and observational study in Mexico. Patients received pantoprazole-Mg 40 mg once daily during 4 weeks. Symptoms were assessed through a physician-administered structured interview and the patient-completed ReQuest in Practice™ questionnaire. Night-time GERD was defined as arousal from sleep during the night due to GERD-associated symptoms. RESULTS: Out of 4,343 patients included at basal visit, 3,665 were considered for the effectiveness per protocol analysis. At baseline, patients had a median of 8 GERD related symptoms. Patients with night-time GERD symptoms (42.7%) were more likely to have extra-esophageal symptoms (P < 0.001) than other GERD patients. Pantoprazole-Mg 40 mg once daily for 4 weeks improved a broad range of GERD-associated symptoms from baseline (80% reduction on physicians assessments; 68-77% reduction on ReQuest in Practice™ dimensions), including both day- and night-time GERD symptoms; improvements were the greatest for extra-esophageal symptoms in patients with night-time symptoms. Pantoprazole-Mg was well tolerated. CONCLUSIONS: Pantoprazole-Mg 40 mg significantly improved a broad range of esophageal and extra-esophageal GERD related symptoms including sleep disturbances, as well as well-being, in patients with daytime or night-time GERD, making it a good option for patients with GERD, especially when extra-esophageal and night-time symptoms are present.

Efficacy, safety, and tolerability of pantoprazole magnesium in the treatment of reflux symptoms in patients with gastroesophageal reflux disease (GERD): a prospective, multicenter, post-marketing observational study.

BACKGROUND: To improve proton pump inhibitor effects, pharmacological modifications have been developed such as the use of enantiomer molecules (e.g., S-omeprazole, S-pantoprazole, or dexlansoprazole), or addition of NaHCO3 (for an immediate release) or magnesium (with a lower absorption for a more sustained effect). OBJECTIVE: The objective of this study was to assess the efficacy, safety, and tolerability of pantoprazole magnesium 40 mg once daily for 4 weeks, on the relief of reflux symptoms in gastroesophageal reflux disease (GERD) patients. METHODS: A phase IV, open-label, prospective, multicenter study was designed. Patients included were prescribed pantoprazole magnesium 40 mg orally once daily for 28±2 days. All patients had a history of persistent or recurrent heartburn and/or acid regurgitation for at least 3 months. Effectiveness and tolerability data obtained from patients who completed a minimum of 4 weeks of pantoprazole magnesium treatment were considered for analysis. RESULTS: The account of baseline characteristics and demographics of GERD symptom intensity was made by analyzing the group of 4,343 patients that fulfilled all inclusion criteria; 54% were females (n=2,345) and 46% (n=1,998) males, with a mean age of 36.2±7.5 years. Severity of symptoms, assessed by the physician using the 4-point Likert scale, reduced by at least 80% from baseline intensity after treatment in the per protocol population. In the case of the intention-to-treat population, the improvement in symptom intensity was 73%. The number of patients that experienced any adverse events was 175/5,027 (3.48%). CONCLUSIONS: Pantoprazole magnesium is a safe, effective, and well-tolerated drug that significantly improves GERD symptoms.

Proton pump inhibitors in gastroesophageal reflux disease: "a custom-tailored therapeutic regimen".

The Montreal Definition and Classification divides Gastroesophageal Reflux Disease (GERD) into esophageal symptomatic syndromes (and with mucosal damage) and extraesophageal syndromes (with acid established association and proposed association). In typical GERD symptoms, an 8-week treatment with PPIs is satisfactory in most cases (> 90%). Response rates to PPIs in GERD are highly variable, as they also rely on an appropriate clinical diagnosis of the disease; endoscopy differentiates the macroscopic GERD phenotype. The non-erosive variety (50-70% prevalence) has a different symptomatic response rate, as gastric acid is not the sole etiology of symptoms. The possible explanations of treatment failure include treatment adherence, PPI metabolism alterations and characteristics, and inadequate diagnosis. Refractory symptoms are related to gastric content neutralization by the chronic use of PPIs.Extraesophageal manifestations are associated with other pathophysiological mechanisms where an autonomic nervous system disturbance gives rise to symptoms. In these clinical entities, the relationship between symptoms and acid needs to be established in order to determine the use of PPIs, or consider other drugs. In other words, so as to "custom-tailor the best-fitting therapy" we need to answer the questions for whom, for what, how and for how long. Finally, PPI safety and tolerability are factors to be considered in elderly patients requiring chronic PPI use, who usually have chronic concomitant illnesses.

Distal esophageal hypercontractility is related to abnormal acid exposure.

BACKGROUND AND AIMS: Nutcracker esophagus (NE) is a frequent primary motility disorder of the distal esophagus, and the relationship with acid exposure remains controversial. We studied simultaneous distal esophageal hypercontractility (EH) using two sensors at 8 and 3 cm above the lower sphincter (LES) and abnormal exposure to acid (pH DeMeester score). METHODS: From 400 screened patients with chest pain and heartburn, 54 (age 44.5 ± 8.8 years and 74% females) had abnormal manometry and underwent acid exposure measurement. Frequencies of the EH disorder were classic NE (EH(3 cm)) found in 29 (40.8%) patients, diffuse (EH(3,8 cm)) in 30 patients (42.3%), and upper segmental (EH(8 cm)) in 12 patients (16.9%). RESULTS: We found a positive correlation among age with high amplitude in EH(3 cm) and EH(3,8 cm). DeMeester's score (DMS) had the lowest value for EH(3,8 cm) (2.58 ± 0.23) compared with EH(8 cm) (3.78 ± 0.3, p <0.003) and EH(3 cm) (3.12 ± 0.2, p <0.06). Surface response for joint effect of age and DMS on amplitude at EH(3 cm) confirmed the highest amplitude was for older age and lower DMS. CONCLUSIONS: EH(3 cm) and EH(3,8 cm) were common for esophageal motility and were inversely associated with DMS. Meanwhile, acid exposure was higher in younger patients and hypercontractility was more frequent in older subjects. The former group may benefit more from proton pump inhibitors and the latter from visceral analgesics or possibly both.

[Utility of rabeprazole as a diagnostic test in non-erosive gastroesophageal reflux disease]. / Utilidad del rabeprazol como prueba diagnóstica en la enfermedad por reflujo gastroesofágico no erosiva.

BACKGROUND: Proton pump inhibitor test (PPIt) has been shown adequate diagnostic usefulness and cost-effectiveness in the evaluation of patients with gastroesophageal reflux disease (GERD). However, comparative studies of PPIt with 24 hr esophageal pH-metry (24-pH) in non erosive GERD (NERD) are scarce and the utility of rabeprazole as a PPIt has not been evaluated. OBJECTIVE: To investigate the diagnostic utility of rabeprazole test in patients with NERD. MATERIAL AND METHODS: An open label trial was performed, and NERD patients with heartburn at least 3 times per week were included. Symptomatic evaluation before, during and after rabeprazole 20 mg bid for 7 days was performed. All patients underwent 24-pH before treatment with rabeprazole. Patients were classified in three groups: 1) abnormal pH, 2) normal pH and symptom index (SI) positive, and 3) normal pH and SI negative. A positive rabrepazole test was considered when symptoms improvement was higher than 50% at the end of the test. Sensitivity, specificity, negative predictive value, positive predictive value and positive likelihood ratio were calculated considering the 24-pH as gold standard. RESULTS: Sixty four patients, 47 (72%) female were studied. Forty four percent of the patients had normal pH, 29% with SI positive and 71% with SI negative. Sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio were 82%, 47%, 78%, 52% and 1.406 respectively. No adverse events were reported. CONCLUSION: PPI test with rabeprazole 20 mg bid for 7 days is a simple and useful test in the diagnostic approach of patients with NERD.

[Non-erosive gastroesophageal reflux disease. Incidence of clinical forms, characteristics of esophageal exposure to acid and symptomatic correlations]. / Enfermedad por reflujo gastroesofágico no erosiva. Frecuencia de sus variedades clínicas, características de la exposición esofágica al ácido y correlación sintomática.

BACKGROUND: It is estimated that up to 70% of community-based patients with heartburn have no evidence of esophageal mucosal injury or non-erosive gastroesophageal reflux disease (NERD). Studies in NERD patients using esophageal pH monitoring and symptom index (SI) have suggested different subgroups or clinical forms. OBJECTIVE: Our aim was to investigate frequency of different subgroups of patients with NERD according to esophageal pH-monitoring parameters and SI, and to determine esophageal acid exposure characteristics and the relationship between symptoms and acid reflux in NERD. MATERIAL AND METHODS: Patients with heartburn at least 3 times per week during 12 weeks during the last year and negative upper GI endoscopy were studied. All patients were submitted to 24 h esophageal pH-metry and SI was calculated. Patients were classified into three groups: group I, patients with abnormal pH-metry; group II, patients with normal pH-metry and positive SI (> or = 50%), and group III, patients with normal pH-metry and negative SI (< 50%). Total number of reflux episodes, length of episode, % time pH < 4, and Johnson-DeMeester score were evaluated. RESULTS: Three hundred patients, 206 women and 94 men, were included. A total of 137 (46%) were classified in group I, 62 (21%) in group II, and 101 (33%) in group III. There were no significant differences in gender and age among groups. All pH parameters were significantly higher in group I. In group II, there was good correlation between heartburn and acid reflux. Esophageal acid exposure in group III was minimal and there was no relationship among symptoms and acid reflux episodes. CONCLUSIONS: Subjects with NERD represent a heterogeneous group of patients. Three subgroups of patients with NERD were identified by pH-metry and SI; a) patients with abnormal acid exposure; b) patients with hypersensitive esophagus (heartburn with physiologic amounts of acid reflux), and c) patients with no correlation between symptoms and acid reflux.