Limited ability of the proton-pump inhibitor test to identify patients with gastroesophageal reflux disease.

BACKGROUND & AIMS: The efficacy of proton-pump inhibitor (PPI) therapy often is assessed to determine whether patients' symptoms are acid-related and if patients have gastroesophageal reflux disease (GERD), although the accuracy of this approach is questionable. We evaluated the diagnostic performance of the PPI test, in conjunction with other tests, for the diagnosis of GERD. METHODS: We analyzed data from the DIAMOND study, a multinational trial that compared the ability of the reflux disease questionnaire with that of symptom-based clinical diagnosis to identify GERD in primary care patients with frequent upper-gastrointestinal symptoms. Patients (n = 308) were given placebo and further evaluated by endoscopy, wireless esophageal pH-metry, and symptom association monitoring. Those with GERD (n = 197) were identified based on the presence of reflux esophagitis, esophageal pH level less than 4 for more than 5.5% of 24 hours, or positive results from symptom association monitoring (or a positive result from the PPI test in patients with borderline levels of esophageal acidity). All patients then were given single-blind therapy with esomeprazole (40 mg once daily) for 2 weeks and symptoms were recorded daily. RESULTS: A positive response to the PPI test was observed in 69% of patients with GERD and in 51% of those without GERD. Response to placebo did not influence the diagnostic ability of the subsequent PPI test. More patients with reflux esophagitis had a positive result from the PPI test than patients without GERD (57% vs 35%; P = .002) or patients with GERD but no esophagitis. A clinical diagnosis by the primary care physician of an acid-related disease was not associated with response to PPIs. CONCLUSIONS: In a well-characterized population of primary care patients with frequent upper-gastrointestinal symptoms of any type, the PPI test has limited ability to identify patients with GERD, diagnosed by current standard tests. (ClinicalTrials.gov Number, NCT00291746.).

Accuracy of the diagnosis of GORD by questionnaire, physicians and a trial of proton pump inhibitor treatment: the Diamond Study.

OBJECTIVE: The aim of this study was to determine the accuracy of the diagnosis of gastro-oesophageal reflux disease (GORD) by the Reflux Disease Questionnaire (RDQ), family practitioners, gastroenterologists and a test of esomeprazole therapy. METHODS: This was a single-blind, single-arm study over 3-4 weeks from September 2005 to November 2006. Each symptom-based diagnostic assessment was made blinded to prior diagnoses. Patients were those presenting to their family practitioner with troublesome upper gastrointestinal symptoms (n=308). The RDQ was completed and a symptom-based diagnosis was made by the family practitioner. Placebo esomeprazole was started. Gastroenterologists made a symptom-based diagnosis and then performed endoscopy with 48 h oesophageal pH and symptom association monitoring to determine the presence/absence of GORD. Symptoms were recorded during treatment with 40 mg of esomeprazole for 2 weeks. The main outcome measure was RDQ scoring for the presence of GORD compared with symptom-based diagnosis by family physicians and gastroenterologists. RESULTS: GORD was present in 203/308 (66%) patients. Only 49% of the patients with GORD selected either heartburn or regurgitation as the most troublesome symptom. Sensitivity and specificity, respectively, of the symptom-based diagnosis of GORD, were 62% and 67% for the RDQ, 63% and 63% for family practitioners, and 67% and 70% for gastroenterologists. Symptom response to esomeprazole was neither sensitive nor specific for the diagnosis of GORD. CONCLUSIONS: The RDQ, family practitioners and gastroenterologists have moderate and similar accuracy for diagnosis of GORD. Symptom response to a 2 week course of 40 mg of esomeprazole does not add diagnostic precision.

Prevention of relapse of healed reflux esophagitis is related to the duration of intragastric pH > 4.

Proton pump inhibitors (PPIs) are the preferred treatment for maintenance of healed reflux esophagitis (RE). However, little is known regarding the relationship between prevention of RE relapse and degree of gastric acid suppression. The aim of this review was to examine this relationship in further detail. Data from four comparative studies on maintenance PPI therapy for prevention of relapse of RE were combined with data from two pharmacodynamic studies of duration of intragastric pH >4 during the 24-hour period on day 5 of PPI dosing in healthy subjects. A log-linear model was fitted to the data using the method of maximum likelihood. Variability in relapse rates and pH data was taken into account using a binomial and normal likelihood function, respectively. Pharmacodynamic studies resulted in a wide range of acid-suppressive effect, and based on corresponding maintenance of RE healing rates with different PPIs and doses, an inverse (non-linear) statistically significant relationship between percentage of time with pH >4 and maintenance of RE healing was identified (P<0.001). These findings indicate that long-term maintenance of healed RE is related to the extent of acid suppression in a 24-hour period.

Effect of esomeprazole 40 mg once or twice daily on asthma: a randomized, placebo-controlled study.

RATIONALE: Gastroesophageal reflux disease (GERD) is common among patients with asthma; however, studies investigating the effect of proton pump inhibitors on asthma outcomes report conflicting results. OBJECTIVES: To investigate the effect of esomeprazole 40 mg once or twice daily on asthma outcomes in patients with concomitant symptoms of GERD. METHODS: This 26-week, randomized, double-blind, placebo-controlled study (NCT00317044) included adult patients (18-70 yr) with moderate-to-severe asthma and symptomatic GERD. The change in morning peak expiratory flow (primary variable), evening peak expiratory flow, FEV(1), asthma symptoms, Asthma Quality of Life Questionnaire, Reflux Disease Questionnaire, and tolerability were assessed. MEASUREMENTS AND MAIN RESULTS: A total of 961 patients were randomized and 828 completed the study. Relative to baseline, improvement in morning peak expiratory flow was observed for both esomeprazole 40 mg once daily (+3.5 L/min; 95% CI, -3.2 to 10.2) and 40 mg twice daily (+5.5 L/min; 95% CI, -1.2 to 12.2), although no statistically significant between-treatment differences were apparent. At treatment end, both doses of esomeprazole significantly improved FEV(1) versus placebo (+0.09 L and +0.12 L; P = 0.0039 and P < 0.0001, respectively). However, only esomeprazole 40 mg twice daily demonstrated a significant improvement when FEV(1) was calculated over the entire 26-week period (+0.07 L; P = 0.0042). Significant improvements in Asthma Quality of Life Questionnaire total score were demonstrated for both esomeprazole doses compared with placebo (+0.28 and +0.41; P = 0.0006 and P < 0.0001, respectively). CONCLUSIONS: Esomeprazole may improve pulmonary function and asthma-related quality of life. However, the improvements were minor and of small clinical significance.

Long-term outcome of microscopic esophagitis in chronic GERD patients treated with esomeprazole or laparoscopic antireflux surgery in the LOTUS trial.

OBJECTIVES: Gastroesophageal reflux disease (GERD)-associated changes in esophageal histology have been reported mainly after short-term medical antireflux therapy, and few individual lesions have been examined. We report detailed histological findings from the LOTUS study, at baseline and at 1 and 3 years after laparoscopic antireflux surgery (LARS) or esomeprazole treatment in patients with chronic GERD. METHODS: LOTUS is a long-term, open, parallel-group, multicenter, randomized, controlled trial conducted in 11 European countries that compared LARS (n=248) with esomeprazole 20-40 mg daily (n=266). Biopsies from the distal esophagus 2 cm above the Z-line and at the Z-line were taken at baseline, and 1 and 3 years. The following lesions were assessed: basal cell hyperplasia (BCH), papillary elongation (PE), intercellular space dilatations (ISDs), intraepithelial eosinophils (EOSs), neutrophils, and necrosis/erosion. A severity score (SS, range 0-2) was calculated by taking the average score of all assessable lesions. RESULTS: All lesions were more severe on Z-line biopsies than at 2 cm, and almost all improved significantly from baseline to 1 and 3 years. The average SS (from 2 cm to Z-line) changed from 0.95 to 0.57 (1 year) and to 0.49 (3 years) on esomeprazole, and from 0.91 to 0.56 (1 year) and to 0.52 (3 years) after LARS (P<0.001 for both treatments at 1 and 3 years, with no significant difference between treatments). The proportions of patients with severe histological changes decreased from approximately 50% at baseline to 11% at 3 years. CONCLUSIONS: Both continuous esomeprazole treatment and laparoscopic fundoplication are associated with significant and similar overall improvement in microscopic esophagitis after 1 year that is maintained at 3 years.

The Reflux Disease Questionnaire: a measure for assessment of treatment response in clinical trials.

BACKGROUND: Critical needs for treatment trials in gastroesophageal reflux disease (GERD) include assessing response to treatment, evaluating symptom severity, and translation of symptom questionnaires into multiple languages. We evaluated the previously validated Reflux Disease Questionnaire (RDQ) for internal consistency, reliability, responsiveness to change during treatment and the concordance between RDQ and specialty physician assessment of symptom severity, after translation into Swedish and Norwegian. METHODS: Performance of the RDQ after translation into Swedish and Norwegian was evaluated in 439 patients with presumed GERD in a randomized, double-blind trial of active treatment with a proton pump inhibitor. RESULTS: The responsiveness was excellent across three RDQ indicators. Mean change scores in patients on active treatment were large, also reflected in effect sizes that ranged from a low of 1.05 (dyspepsia) to a high of 2.05 (heartburn) and standardized response means 0.99 (dyspepsia) and 1.52 (heartburn). A good positive correlation between physician severity ratings and RDQ scale scores was seen. The internal consistency reliability using alpha coefficients of the scales, regardless of language, ranged from 0.67 to 0.89. CONCLUSION: The results provide strong evidence that the RDQ is amenable to translation and represents a viable instrument for assessing response to treatment, and symptom severity.

Validation of a four-graded scale for severity of heartburn in patients with symptoms of gastroesophageal reflux disease.

OBJECTIVES: To evaluate the reliability, responsiveness, and validity of a four-graded symptom severity scale (none, mild, moderate, severe) and an eight-graded frequency scale (number of days with symptoms during past week) for assessment of heartburn severity and frequency in patients with symptoms of heartburn but without esophagitis. METHODS: Data were taken from two 4-week clinical trials comparing esomeprazole 20 mg and/or 40 mg to omeprazole 20 mg. Both scales were analyzed in terms of mean scores and treatment success rates, after dichotomization to "treatment success" variables. RESULTS: Heartburn severity reliability was higher when assessed by patient diary cards than by the investigator (intraclass correlation coefficients were 0.79 and 0.59, respectively; corresponding figures for heartburn frequency were 0.77 and 0.78). There was good agreement between investigator and diary card assessments for the dichotomized variables "complete resolution" and "adequate relief" from heartburn. High correlation between investigator- and diary card-assessed heartburn severity and frequency was apparent. Responsiveness was high, as shown by comparing 4-week treatment success rates to the patients' perception of treatment effect according to the Overall Treatment Effect questionnaire. Construct validity was good (kappa values approximately 0.70 for agreement between complete resolution and the dichotomized Gastrointestinal Symptom Rating Scale [GSRS] Heartburn item). correlations between heartburn severity and frequency and the GSRS Heartburn item were similarly high. CONCLUSION: The four-graded heartburn severity and eight-graded frequency scales are reliable, responsive, and valid when used in clinical trials of patients with symptoms of gastroesophageal reflux disease, irrespective of the type of assessment (investigator assessment or patient diary cards).

Standardization of surgical technique in antireflux surgery: the LOTUS Trial experience.

BACKGROUND: To date, it has been difficult to compare medical therapy for gastroesophageal reflux disease with that of surgical management from a scientific viewpoint, mainly because of the lack of standardization of the operative technique. This study was designed to identify a methodology for standardization of surgical technique and to measure the effectiveness of this standardization. METHODS: Surgeons contributing to a major international multicenter trial comparing optimum medical therapy with surgical therapy for treatment of gastroesophageal reflux attempted to optimize their surgical techniques so that a realistic comparison could be made that may aid clinical decision-making. The surgeons met, shared their techniques using video, and produced a standardized set of criteria for the surgical centers and a common operative technique. Data collection methods ensured accuracy of the records of the procedure applied and the data were analyzed for consistency with set surgical standards. RESULTS: There was a high degree of conformity (>95%) between the recommended method of performing a Nissen fundoplication as defined in the trial protocol, and variations were restricted to isolated individuals. The operations were completed without mortality, few conversions, and with very low postoperative morbidity. CONCLUSIONS: This study has shown that, contrary to commonly held belief, surgeons are able to standardize their work for the purposes of measuring the outcome of an operative procedure within the context of a randomized, controlled trial.

Responsiveness of measures of heartburn improvement in non-erosive reflux disease.

BACKGROUND: When measuring treatment effect on symptoms, the treatment success variable should be as responsive as possible. The aim of the study was to investigate the responsiveness of various treatment success variables in patients with symptoms of heartburn. METHODS: A total of 1640 patients with non-erosive reflux disease (NERD) were treated with proton pump inhibitors for 4 weeks. Treatment success variables were based on a symptom questionnaire (Gastrointestinal Symptom Rating Scale) and on investigator-assessed heartburn, measured at baseline and after 4 weeks of treatment. The rates of treatment success were compared with patients' perceived change in symptoms, assessed by the Overall Treatment Effect questionnaire. RESULTS: Generally, more stringent treatment success criteria (i.e., those demanding the better response) translated into more responsive treatment success variables. For example, the treatment success variable 'no heartburn' at 4 weeks was more responsive than the variable 'at most mild heartburn' at 4 weeks. Treatment success variables based on change from baseline to 4 weeks were, in general, less responsive than those based on the week 4 assessments only. CONCLUSION: In patients with NERD, responsiveness varied among different treatment success definitions, with more demanding definitions (based on the 4-week assessment) giving better responsiveness.

Effect of baseline symptom severity on patient-reported outcomes in gastroesophageal reflux disease.

OBJECTIVE: Patient-reported outcome instruments are becoming increasingly important tools in clinical trials. We aimed to investigate the effect of baseline symptom severity on: (i) a global rating of change using the Overall Treatment Effect questionnaire; (ii) the change from baseline for some commonly used questionnaires, namely the Gastrointestinal Symptom Rating Scale and the Quality of Life in Reflux and Dyspepsia questionnaire; and (iii) treatment differences assessed by Gastrointestinal Symptom Rating Scale in patients with symptoms of gastroesophageal reflux disease. METHODS: We used pooled data from two 4-week studies of patients with gastroesophageal reflux disease (but without endoscopically verified esophagitis) randomized either to esomeprazole (20 or 40 mg) or to omeprazole 20 mg. We also used data from a study of omeprazole (10 or 20 mg) or ranitidine 300 mg in gastroesophageal reflux disease patients with or without esophagitis. The analysis is based on descriptive statistics. RESULTS: Little impact of baseline symptoms/problems exists on the global rating of change (Overall Treatment Effect questionnaire). For example, the percentage of patients experiencing a large improvement with acid-suppressive therapy according to Overall Treatment Effect ranged from 63.2% for those with mild reflux at baseline to 70.3% for those with severe reflux. Change from baseline in the Gastrointestinal Symptom Rating Scale reflux dimension and quality of life in reflux and dyspepsia sleep disturbance and food/drink problems dimensions were associated with baseline symptoms/problems, with the largest change seen for patients with severe symptoms/problems at baseline. Baseline symptom severity was also associated with a clear effect on treatment differences, which tended to be larger for patients with severe symptoms than for patients with mild baseline symptoms. CONCLUSIONS: In patients with gastroesophageal reflux disease, baseline symptom/problem severity had little association with the global rating of change, whereas a clear association with change in symptoms/problems and on treatment differences was apparent. The magnitude of change increased with increasing baseline severity of symptoms/problems.

The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria.

BACKGROUND & AIMS: Barrett's esophagus (BE) is a premalignant condition for esophageal adenocarcinoma, its diagnosis relying initially on recognition of a columnar-lined distal esophagus. We aimed to develop and validate explicit, consensus-driven criteria for the endoscopic diagnosis and grading of BE. METHODS: An international working group agreed on criteria and developed materials for their formal evaluation using video-endoscopic recordings gathered in a standardized manner in 29 patients. The criteria included assessment of the circumferential (C) and maximum (M) extent of the endoscopically visualized BE segment as well as endoscopic landmarks. The recordings were scored according to these criteria by a separate international panel of 29 endoscopists. RESULTS: The Prague C & M Criteria give explicit guidance on the endoscopic recognition of BE and grading of its extent. The overall reliability coefficients (RC) for the assessment of the C & M extent of the endoscopic BE segment above the gastroesophageal junction were 0.95 and 0.94, respectively. The rates of exact agreement (for C & M values) for pairwise comparisons of individual patient values were 53% and 38%, respectively, whereas the values for agreement within a 2-cm interval were 97% and 95%, respectively. The overall RC for endoscopic recognition of BE >/=1 cm was 0.72, whereas for BE <1 cm, it was 0.22. The RCs for recognizing the location of the gastroesophageal junction and the diaphragmatic hiatus were 0.88 and 0.85, respectively. CONCLUSIONS: The Prague C & M Criteria have high overall validity for the endoscopic assessment of visualized BE lengths.

Assessing symptoms in gastroesophageal reflux disease: how well do clinicians' assessments agree with those of their patients?

OBJECTIVES: This study aimed to determine the extent of agreement between clinicians and patients regarding assessments of reflux symptom severity in patients with gastroesophageal reflux disease. METHODS: Data were analyzed from four randomized clinical trials involving 2,674 patients treated with esomeprazole, omeprazole, ranitidine, or placebo. The extent of agreement was determined for symptom severity before and after 4-8 wk of treatment, and for the absence of symptoms after treatment. Agreement was further analyzed by determining weighted kappa values, which were interpreted according to the criteria of Landis and Koch. RESULTS: Before treatment, clinician-patient agreement regarding symptom severity in the four studies was slight to moderate (kappa: 0.17-0.53); 48-52% of assessments agreed for heartburn, 24-35% for epigastric pain, 36-43% for regurgitation, and 63% agreed for dysphagia. Poor agreement reflected clinician underestimation of symptom severity relative to patient ratings in three studies and clinician overestimation in one study. Agreement regarding symptom severity improved following treatment, and was fair to substantial (kappa: 0.31-0.73); 58-78% of assessments agreed for heartburn, 42-60% for epigastric pain, 66-76% for regurgitation, and 86% agreed for dysphagia. After treatment, agreement was greatest for patients reporting absence of symptoms and decreased with increasing severity of symptoms. CONCLUSIONS: The agreement between clinicians and patients in their assessments of the severity of reflux symptoms is poor, particularly before treatment and for more severe symptoms. Improvements in clinician-patient communication may help to bridge this gap, and greater reliance on patient assessments may be appropriate.

Esomeprazole 40 mg provides improved intragastric acid control as compared with lansoprazole 30 mg and rabeprazole 20 mg in healthy volunteers.

AIM: To compare the effects of standard-dose esomeprazole with those of standard doses of lansoprazole and rabeprazole on intragastric pH during repeated daily oral dosing in healthy volunteers. METHODS: In two standardized, randomized crossover studies, Helicobacter pylori negative healthy volunteers (study A: 19 males, 5 females; study B: 13 males, 10 females) received esomeprazole 40 mg and either lansoprazole 30 mg (study A) or rabeprazole 20 mg (study B) orally once daily in the morning for 5 days. Continuous 24-hour intragastric pH recording was performed on day 5. RESULTS: The intragastric pH was maintained >4 for 65% (95% CI 59.5-71.3) of the 24-hour period with esomeprazole and for 53% of the time (95% CI 47.0-58.9) with lansoprazole in study A (p < 0.001). In study B, the proportion of time with pH >4 was 61% (95% CI 53.6-68.3) with esomeprazole versus 45% (95% CI 37.7-52.5) with rabeprazole (p = 0.005). The 24-hour median pH and the proportion of volunteers with intragastric pH >4 for > or =12 h and > or =16 h were significantly higher with esomeprazole than with either lansoprazole or rabeprazole. CONCLUSION: Esomeprazole 40 mg provides significantly more effective and more sustained gastric acid control than lansoprazole 30 mg or rabeprazole 20 mg in healthy volunteers.

Factor structure of the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire evaluated in patients with heartburn predominant reflux disease.

AIM: To test whether the original factor structure of the Quality of Life in Reflux and Dyspepsia (QOLRAD) can be replicated in Nordic patients and English speaking patients. PATIENTS AND METHODS: Clinical trial patients with heartburn without esophagitis completed the Swedish, Norwegian, Finnish and Danish versions (n = 634) and the English version (n = 1185). The factor structure was examined using models generated by exploratory and confirmatory factor analysis. RESULTS: The exploratory factor analysis suggested that the original five-factor structure solution was the most optimal. The Nordic versions explained 67% and the English version 72% of the variance. The factor loading of 22 out of 25 items was >0.55. In the confirmatory factor analysis, because of the sample size, only the Swedish and Norwegian data were used. Confirmatory factor analysis indicated an acceptable goodness of fit of the five-factor solution to the data with a goodness of fit index of 0.85 in the Swedish, 0.77 in the Norwegian and 0.91 in the English speaking population. The internal consistency reliability ranged from 0.70 to 0.94 (in the Nordic translations) and from 0.85 to 0.92 (in the English version), supporting the homogeneity of the items within the factors and thus their construct validity. The QOLRAD distinguished severity and frequency of heartburn, thereby documenting its known-group validity to distinguish between groups of patients. CONCLUSIONS: The factor structure and dimensionality of the English version and the Swedish and Norwegian translations of the QOLRAD could be replicated by the exploratory and confirmed by the confirmatory factor analysis. The QOLRAD is a valid and reliable instrument for use in clinical trials.

The effect of the area under the plasma concentration vs time curve and the maximum plasma concentration of esomeprazole on intragastric pH.

OBJECTIVE: The aim of this study was to create a useful model of the effect of the area under the plasma concentration vs time curve (AUC) and the maximum plasma concentration (C(max)) of esomeprazole on intragastric pH, measured as the percentage of total time with intragastric pH above 4 (%pH>4) during a 24-h period. METHODS: The evaluation is based on esomeprazole data from two crossover studies. In the first study ( n=36), intragastric pH and plasma concentrations were measured on day 5 of repeated once-daily 20-mg and 40-mg doses of esomeprazole during fasting conditions. In the second study ( n=24), measurements were made on days 1 and 5 of repeated once-daily dosing with 40 mg of esomeprazole under fasting and fed conditions. A model was applied in which the logistic function of %pH>4 was assumed to be linearly dependent on log-transformed AUC and C(max). The effects of repeated dosing and of fed relative to fasting conditions were included in the model, and the interindividual variation in %pH>4 was accounted for. RESULTS: The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error. In this model, log-transformed AUC and C(max) were both statistically significant. The model showed that for a fixed AUC, a decrease in C(max) gives an increase in %pH>4. A decrease in AUC, keeping C(max) fixed, gives a decrease in %pH>4, but a simultaneous decrease in C(max) and AUC will result in a less pronounced decrease in %pH>4. The model may be used for predicting differences in %pH>4 between two formulations, based on assessments of AUC and C(max). Repeated dosing gave an increased %pH>4, where approximately half of the increase stemmed from increased AUC and C(max), and the rest could be attributable to the persistent blockade of the proton pumps. Food intake reduced AUC and C(max) but had no obvious effect on %pH>4, which is explained by a prolonged time period with quantifiable plasma concentrations. CONCLUSION: The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error.

Cost effectiveness of esomeprazole compared with omeprazole in the acute treatment of patients with reflux oesophagitis in the UK.

BACKGROUND: Clinical studies have demonstrated that esomeprazole is superior to omeprazole for the acute treatment of reflux oesophagitis. OBJECTIVE: To compare the cost effectiveness of esomeprazole 40mg once daily with omeprazole 20mg once daily in patients with reflux oesophagitis. METHODS: Pooled data were used from three 8-week clinical trials comparing the efficacy and safety of esomeprazole 40mg once daily and omeprazole 20mg once daily for the acute treatment of reflux oesophagitis. A simple decision analysis model, using UK direct medical costs, compared the cost effectiveness of the two treatments. Healing probabilities derived from the clinical studies using the Life Table method were used to estimate the effectiveness and cost of treating 100 patients with reflux oesophagitis. Patient management assumptions were based on a clinical management survey involving 25 UK physicians. PERSPECTIVE: UK National Health Service. RESULTS: After 4 weeks' therapy, the Life Table estimated the oesophageal healing rate to be 77.7% in esomeprazole 40mg once-daily recipients (n = 2446), compared with 67.6% in omeprazole 20mg once-daily recipients (n = 2431; p < 0.001). The corresponding values after 8 weeks' treatment were 93.4% and 86.2%, respectively (p < 0.001). The model predicted that when considering healing probabilities over 8 weeks, esomeprazole 40mg once daily produced total direct cost savings of pound1290 (14%) when compared with omeprazole 20mg once daily. When considering the cost of treating patients who had failed treatment (defined as patient not healed as assessed by endoscopy) after 8 weeks, the cost advantage for esomeprazole was even greater. CONCLUSION: Esomeprazole 40mg once daily is cost effective compared with omeprazole 20mg once daily in the acute treatment of patients with reflux oesophagitis; esomeprazole provides greater effectiveness at a lower cost.

Cost effectiveness of proton pump inhibitors in gastro-oesophageal reflux disease without oesophagitis: comparison of on-demand esomeprazole with conventional omeprazole strategies.

OBJECTIVES: To evaluate the cost effectiveness of on-demand treatment with esomeprazole 20mg compared with two alternative omeprazole treatment strategies for the long-term management of patients with gastro-oesophageal reflux disease (GORD) without oesophagitis. DESIGN: A simple Markov model was designed to compare the cost effectiveness of on-demand esomeprazole 20mg therapy for 6 months with a strategy consisting of intermittent 4-week acute treatment courses of omeprazole 20mg once daily or a strategy consisting of continuous omeprazole treatment (20mg once daily) following acute treatment of first relapse while on no drug treatment (a commonly used conventional care strategy). Relapse probabilities were based on pooled results from two 6-month placebo-controlled clinical studies of on-demand esomeprazole 20mg treatment in patients with GORD without oesophagitis and on results from a GORD study with a 6-month untreated follow-up. The expected number of relapses per patient was used as the effectiveness measure. SETTING AND PERSPECTIVE: Patient management assumptions were based on a UK physician survey. The cost-effectiveness analysis considered UK direct medical costs from the perspective of the National Health Service. RESULTS: The pooled analysis showed that after 6 months treatment, 90% of patients could control symptoms effectively with on-demand esomeprazole 20mg. The expected number of relapses per patient was estimated at 0.10 for on-demand esomeprazole, 0.57 to 1.12 for intermittent omeprazole and 0.47 to 0.75 for conventional omeprazole treatment. The esomeprazole strategy incurred considerably lower direct medical costs (16 to 61%) than either omeprazole strategy. CONCLUSION: On-demand treatment with esomeprazole 20mg is cost effective compared with two alternative omeprazole treatment strategies in patients with GORD without oesophagitis.