Aliment Pharmacol Ther 2012; 35: 154–164
Summary
Background The evolution of gastro‐oesophageal reflux disease (GERD) under current management options remains uncertain.
Aim To examine whether, ...depending on the initial presentation, non‐erosive (NERD) and erosive reflux disease (ERD) without Barrett’s oesophagus will progress to more severe disease under current routine care following the resolution of the initial condition.
Methods Patients with the primary symptom of heartburn were included at baseline, and stratified into non‐erosive (NERD) and erosive reflux disease (ERD), LA grades A–D (Los Angeles classification). After a 2‐ to 8‐week course with esomeprazole therapy to achieve endoscopic healing in ERD and symptom relief in NERD, patients were treated routinely at the discretion of their physician. We report oesophagitis status and the presence of endoscopic and confirmed Barrett’s oesophagus after 5 years.
Results A total of 6215 patients were enrolled in the study of whom 2721 patients completed the 5‐year follow‐up. Progression, regression and stability of GERD severity were followed from baseline to 5 years. Only a few patients with NERD and mild/moderate ERD progressed to severe forms of ERD and even Barrett’s oesophagus. Most patients remained stable or showed improvement in their oesophagitis; 5.9% of the NERD patients, 12.1% of LA grade A/B patients and 19.7% of LA grade C/D patients in whom no Barrett’s oesophagus was recorded at baseline progressed to endoscopic or confirmed Barrett’s oesophagus at 5 years.
Conclusion Most GERD patients remain stable or improve over a 5‐year observation period under current routine clinical care.
Summary
Background
Proton pump inhibitors (PPIs) are the treatment of choice for reflux esophagitis (RE). The effectiveness of PPIs throughout RE management, from healing to maintenance, has not been ...fully studied.
Aim
To compare esomeprazole with lansoprazole or pantoprazole for RE management using a management model.
Methods
Data from six studies comparing esomeprazole with lansoprazole or pantoprazole for healing (4–8 weeks) or maintenance of healing (6 months) of RE were incorporated into hypothetical management models to determine the proportion of patients in endoscopic remission after sequential healing and maintenance therapy, assuming that patients received the same PPI throughout. The number needed to treat (NNT) to achieve one more patient in remission with esomeprazole vs. other PPIs was estimated. The hypothetical model was validated using results from the EXPO study, which compared esomeprazole with pantoprazole for RE healing and maintenance.
Results
Overall, esomeprazole 40 mg produced higher rates of healing (life‐table estimates) than lansoprazole 30 mg (82.4–92.6% vs. 77.5–88.8%; p < 0.01) or pantoprazole 40 mg (95.5% vs. 92.0%; p < 0.001) and higher rates of endoscopic and symptomatic remission at 6 months than lansoprazole (83.0–84.8% vs. 74.0–75.9%; p < 0.001; life‐table estimates) or pantoprazole (70.9% vs. 59.6%; p < 0.0001; observed rates). In the hypothetical management model, the NNT for esomeprazole was 9 vs. lansoprazole and 8 vs. pantoprazole. The actual NNT for esomeprazole vs. pantoprazole in the EXPO study was 9 (95% confidence interval: 6; 16).
Conclusions
In this management model, esomeprazole was more effective than either lansoprazole or pantoprazole for maintaining remission after sequential healing and 6 months’ maintenance therapy for RE.
Summary
Background and aims: Gastro‐oesophageal reflux disease (GERD) can be associated with a variety of extra‐oesophageal disorders (EED) such as chronic cough, asthma, laryngeal disorder or chest ...pain. The aim of the study was to estimate and compare the prevalence of EED in a population with symptomatic GERD presenting as either erosive reflux disease (ERD) or non‐erosive reflux disease (NERD).
Methods: Baseline data were collected from a prospective, multicentre, open cohort study (ProGERD) in which patients will be followed for 5 years after initial treatment with esomeprazole. Within the framework of this trial, all patients underwent gastroscopy and filled out a questionnaire designed to assess EED. The influence of potential prognostic factors on the prevalence of EED was analysed by multivariate (stepwise logistic regression) analysis.
Results: 6215 patients (3303 male, 2912 female; mean age 54 years) presenting with heartburn were included. EED was detected in 32.8% of all patients. The proportion was significantly higher (P = 0.0002) in ERD patients (34.9%) than in NERD patients (30.5%). As judged from the multivariate analysis, female gender, age, oesophagitis of LA grade C/D, duration of GERD disease greater than 1 years and smoking were significantly associated with EED. ERD patients with oesophagitis of LA grade A or B did not have a significantly higher risk of EED than patients with NERD.
Conclusions: Patients with GERD have a high probability of experiencing EED, which may be associated with a number of prognostic factors such as duration and severity of GERD. Extra‐oesophageal disorders are slightly, but statistically, more prevalent in ERD than in NERD patients.
Summary
Aims : To determine the impact of gastro‐oesophageal reflux disease (GERD) on the quality of life, to assess changes in the quality of life during treatment with esomeprazole and to define ...factors that can predict these changes.
Methods : Patients with GERD (n = 6215) were included in a prospective cohort study (ProGERD). All patients underwent endoscopy and received esomeprazole. At baseline and after 2 weeks of treatment, symptoms and quality of life were assessed. Factors that influenced changes in the quality of life were determined by multiple regression analyses.
Results : At baseline, the quality of life in GERD patients was lower than that in the general population, and was similar to that in patients after acute coronary events. No differences in symptoms or quality of life were observed between the subgroups of patients with non‐erosive GERD, erosive GERD and Barrett's oesophagus. After treatment with esomeprazole, the symptoms and quality of life were improved in all subscales within 2 weeks (P < 0.001). The mean score of the disease‐specific quality of life instrument (Quality of Life in Reflux and Dyspepsia Patients) increased from 4.6 to 6.2 points, representing a highly relevant clinical improvement. The generic quality of life (SF‐36) reached levels similar to those in the general population, but, again, no difference was found between the three different subgroups of GERD patients. The main factors associated with an improvement in the quality of life after treatment were symptom relief, severe erosive reflux disease, absence of extra‐oesophageal disorders, avoidance of non‐steroidal anti‐inflammatory drug intake and positive Helicobacter pylori status.
Conclusions : GERD causes a significant impairment in the quality of life that can be attenuated or normalized within a time period as short as 2 weeks by treatment with esomeprazole. These findings were similar across the whole GERD patient spectrum.
Summary
Background
As treatments for constipation become increasingly available, it is important to know when to progress along the treatment algorithm if the patient is not better.
Aim
To establish ...the definition of failure of a treatment to provide adequate relief (F‐PAR) to support this management and referral process in patients with chronic constipation.
Methods
We conducted an international Delphi Survey among gastroenterologists and general practitioners with a special interest in chronic constipation. An initial questionnaire based on recognised rating scales was developed following a focus group. Data were collected from two subsequent rounds of questionnaires completed by all authors. Likert scales were used to establish a consensus on a shorter list of more severe symptoms.
Results
The initial focus group yielded a first round questionnaire with 84 statements. There was good consensus on symptom severity and a clear severity response curve, allowing 67 of the symptom‐severity pairings to be eliminated. Subsequently, a clear consensus was established on further reduction to eight symptom statements in the final definition, condensed by the steering committee into five diagnostic statements (after replicate statements had been removed).
Conclusions
We present an international consensus on chronic constipation, of five symptoms and their severities, any of which would be sufficient to provide clinical evidence of treatment failure. We also provide data representing an expert calibration of commonly used rating scales, thus allowing results of clinical trials expressed in terms of those scales to be converted into estimates of rates of provision of adequate relief.
We describe the design and report the first results of the Progression of Gastroesophageal Reflux Disease (ProGERD) study, to our knowledge the largest prospective study of GERD patients.
Patients ...were recruited at 1,253 centers in Germany, Austria, and Switzerland. Following an assessment of medical history, all patients were endoscoped and received esomeprazole for 2 to 8 weeks before entering the 5-year observational phase.
A total of 6,215 patients (53% male, age 54±14) were included. Of these patients, 46% reported at least daily symptoms, 15% were unable to work at least once during the prior year, and 71% had visited a physician due to reflux symptoms. Barrett's esophagus (BE) was found in 11% of our GERD patients. In polychotomous regression analysis, the main factors related to the occurrence of the three GERD subgroups (nonerosive, erosive disease, and BE) were age, gender, duration of GERD, body mass index (BMI), smoking, and previous PPI use. Factors associated with longer disease duration were increasing age, male gender, BMI, increasing symptom severity, presence of erosive GERD or BE, positive family history, and smoking.
The findings indicate that GERD is a great burden for patients, and has significant socioeconomic implications. The long-term follow-up period with further endoscopic and histologic evaluations, will help further our understanding of the natural course of the disease.
Aim:
To compare the effectiveness of Helicobacter pylori eradication in curing peptic ulcer disease in trials involving both gastric ulcer and duodenal ulcer.
Methods:
Twenty‐four relevant randomized ...controlled trials and randomized comparative trials met the predefined selection criteria. Only proton pump inhibitor‐based eradication trials were considered for the evaluation of eradication efficacy and ulcer healing. For the determination of relapse rates, all trials independent of the eradication therapy regimen were considered.
Results:
Data from 2102 patients were analysed comparing gastric ulcer with duodenal ulcer. No statistical differences between gastric ulcer and duodenal ulcer patients were found with regard to eradication rates (summarized odds ratio, 1.23; 95% confidence interval, 0.98–1.55) or ulcer relapse rates, whether in successfully H. pylori eradicated patients (summarized odds ratio, 0.69; 95% confidence interval, 0.26–1.84) or unsuccessfully H. pylori eradicated patients (summarized odds ratio, 1.48; 95% confidence interval, 0.85–2.56). Owing to heterogeneity, healing rates were not comparable.
Conclusions:
The eradication of H. pylori infection cures both gastric and duodenal ulcer, and the cure rates are similar. This suggests that H. pylori is the key factor in peptic ulcer disease independent of the ulcer site.
Summary
Aim : To assess whether the eradication of Helicobacter pylori leads to long‐term relief of symptoms in functional dyspepsia.
Methods : Eight hundred patients with functional dyspepsia were ...randomized to receive double‐blind treatment with twice‐daily 30 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L30AC), twice‐daily 15 mg lansoprazole, 1000 mg amoxicillin and 500 mg clarithromycin for 7 days (L15AC), or once‐daily 15 mg lansoprazole for 14 days (LP). Dyspepsia and reflux symptoms were monitored for 12 months.
Results : In intention‐to‐treat analysis, the non‐ulcer dyspepsia sum score showed a statistically significant benefit in terms of symptom relief in the L30AC group (P = 0.0068) compared with the LP group, but there was no significant difference between the L15AC and LP groups (P = 0.2). When all patients in the two eradication therapy arms were considered together, successful eradication had a significant benefit with regard to the complete absence of symptoms (P < 0.04). H. pylori eradication did not lead to an increase in reflux symptoms.
Conclusion : This study suggests that H. pylori infection causes dyspeptic symptoms in a subset of patients with functional dyspepsia, and that these patients may obtain long‐term symptomatic benefit following H. pylori eradication.
Summary
Background Ability to predict freedom from heartburn relapse during maintenance therapy for healed reflux oesophagitis may facilitate optimal treatment choices for individual patients.
Aim ...To determine factors predicting freedom from heartburn relapse during maintenance proton pump inhibitor therapy in patients with healed reflux oesophagitis.
Methods This post‐hoc analysis used data from the maintenance phase of the EXPO study (AstraZeneca study code: SH‐NEG‐0008); 2766 patients with healed reflux oesophagitis and resolved heartburn received once‐daily esomeprazole 20 mg or pantoprazole 20 mg for 6 months. Multiple logistic regression analysis determined factors associated with freedom from heartburn relapse.
Results Heartburn relapse rates were lower with esomeprazole than pantoprazole in all subgroups analysed. Esomeprazole treatment was the factor most strongly associated with freedom from heartburn relapse (odds ratio 2.08; P < 0.0001). Other factors significantly associated with freedom from heartburn relapse were Helicobacter pylori infection, greater age, non‐obesity, absence of epigastric pain at baseline, pre‐treatment nonsevere heartburn and GERD symptom duration ≤5 years.
Conclusions Several factors predict freedom from heartburn relapse during maintenance proton pump inhibitor therapy for healed reflux oesophagitis, the strongest being choice of proton pump inhibitor. These findings outline the importance of optimizing acid control and identifying predictors of relapse for effective long‐term symptom management in reflux oesophagitis patients.
Summary
Background Gastro‐oesophageal reflux disease (GERD) is a common disorder associated with substantial reductions in health‐related quality of life (HRQL).
Aim To describe patterns of change ...in HRQL during 5 years of follow‐up in a large population of GERD patients.
Methods In 2000, a total of 6215 GERD patients were enrolled in the Progression of GERD (ProGERD) study. During follow‐up, patients received any medication considered necessary. HRQL was assessed yearly with the Short‐Form 36 and the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaires. Associations between patient characteristics and changes in HRQL were analysed using multiple logistic regression models.
Results After 5 years, data on HRQL were available for 4597 (74%) patients. Both generic and disease‐specific HRQL improved after baseline and remained well above baseline levels in the following years. A clinically relevant decrease in QOLRAD scores was reported by 3–5% of patients. According to our multivariate analysis, a decrease in HRQL was associated with a higher reflux symptom load and the presence of night‐time heartburn.
Conclusions Only a small minority of the ProGERD population reported a clinically relevant decrease in HRQL, which was associated most strongly with nocturnal heartburn.
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