A review of the clinical and economic impact of using esomeprazole or lansoprazole for the treatment of erosive esophagitis

BACKGROUND: The use of proton pump inhibitors (PPIs) for the treatment of erosive esophagitis has had a major impact on the prescribing budgets of primary care organizations in the United Kingdom. Assessments of the clinical and economic effectiveness of PPIs would provide useful tools for decision-making. OBJECTIVE: The goal of this study was to review the available preclinical and clinical studies comparing esomeprazole with lansoprazole in the healing and maintenance of erosive esophagitis, and to compare the budgeting impact of the 2 strategies. Comparative tolerability was also reviewed. METHODS: MEDLINE (1966-September 2002) and EMBASE (1980-September 2002) were searched for abstracts and articles reporting comparative studies of esomeprazole and lansoprazole. The search terms used were gastroesophageal reflux disease, reflux esophagitis, and proton pump inhibitor; all comparisons of esomeprazole and lansoprazole at any dose were considered. The database search was supplemented based on the authors' familiarity with the literature. RESULTS: The comparative studies that were identified fell into 4 categories: (1) intragastric acid suppression studies; (2) randomized controlled trials in the healing of erosive esophagitis; (3) randomized controlled trials in the maintenance of erosive esophagitis; and (4) health economic analyses. Based on these studies, when healing doses (esomeprazole 40 mg once daily, lansoprazole 30 mg once daily) and low doses (20 and 15 mg once daily, respectively) were compared, esomeprazole was more efficacious than lansoprazole in suppressing acid in the intragastric compartment (both comparisons, P < 0.05). More patients with erosive esophagitis experienced healing at 4 and 8 weeks with esomeprazole 40 mg once daily than with lansoprazole 30 mg once daily (P < 0.001 at 4 and 8 weeks). At 6 months, remission was maintained in more patients receiving esomeprazole 20 mg once daily than in those receiving lansoprazole 15 mg once daily (P < 0.001). No significant differences in tolerability were noted in clinical trials that directly compared the 2 PPIs. When the cost-effectiveness of esomeprazole treatment was compared with that of lansoprazole treatment in the healing and maintenance of erosive esophagitis, the greater efficacy of esomeprazole translated into potential cost savings and better outcomes. CONCLUSION: The currently available comparative data for esomeprazole and lansoprazole indicate clinical and cost-effectiveness advantages for esomeprazole in the healing and maintenance of erosive esophagitis compared with lansoprazole.     

Gastroesophageal reflux disease: current treatment approaches.

Gastroesophageal reflux disease is a common, usually lifelong, disorder resulting from chronic abnormal exposure of the lower esophagus to gastric contents. Motor dysfunction of the lower esophageal sphincter is the primary cause of this disease. At this writing, no medical therapies can completely resolve abnormal lower esophageal sphincter function; therefore, the treatment of gastroesophageal reflux disease centers on suppression of intragastric acid secretion. Available acid-suppressant medications include proton pump inhibitors, H2-receptor antagonists, and antacids. Of these, the proton pump inhibitors are recognized generally as the mainstays of both short-term and long-term therapy for gastroesophageal reflux disease. All have a low incidence of side effects and are well tolerated by most patients. Five proton pump inhibitors are available currently for patients with gastroesophageal reflux disease. Of these, esomeprazole has shown greater efficacy in controlling intragastric acidity than the others. For patients with erosive esophagitis, esomeprazole has demonstrated higher healing rates and more rapid sustained resolution of heartburn than omeprazole or lansoprazole after up to 8 weeks of once-daily treatment. Because new therapies for gastroesophageal reflux disease are highly effective, patients can be reassured that their disease will be well controlled and their symptoms resolved with a safe and appropriate treatment.     

Esomeprazole, a new proton pump inhibitor: pharmacological characteristics and clinical efficacy

Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor synthesised as an optical isomer to become available for clinical use. Esomeprazole is optically stable in humans with negligible inversion to the R-isomer. Esomeprazole has significantly higher oral bioavailability than omeprazole, resulting in greater acid suppression. In clinical studies, 4 weeks' treatment with 40 mg esomeprazole demonstrated greater healing of all grades of erosive oesophagitis, compared with 20 mg omeprazole (76-82% versus 69-71%) and higher rates of symptom resolution (65-68% versus 58-61%) Furthermore, esomeprazole maintained healing rates of up to 90% over 6 months in erosive oesophagitis. Comparisons with other proton pump inhibitors in oesophagitis are, as yet, unavailable. In patients with endoscopy-negative gastro-oesophageal reflux disease (GERD), on-demand therapy with esomeprazole 20 mg has been shown to be very efficacious compared with placebo, and is well tolerated; however, comparisons with other proton pump inhibitors have not been performed. Long-term use of esomeprazole for up to 12 months in patients with GERD have not raised any significant safety concerns with respect to the development of atrophic gastritis or clinically relevant changes in enterochromaffin-like cells.     

Esomeprazole for acid peptic disorders

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical efficacy, and safety of esomeprazole, a new proton-pump inhibitor (PPI). DATA SOURCES: A MEDLINE search (1966-March 2001) was conducted for relevant literature using the terms esomeprazole, Nexium, and H199/18. Abstracts from the XXXII Nordic Meeting of Gastroenterology and journal articles provided by AstraZeneca were reviewed. STUDY SELECTION AND DATA EXTRACTION: All available studies on the pharmacology, pharmacokinetics, clinical efficacy, and safety of esomeprazole were reviewed. DATA SYNTHESIS: Esomeprazole is a new PPI and is the S-isomer of racemic omeprazole. Esomeprazole has demonstrated acid control comparable to that of the other PPIs currently available. Esomeprazole undergoes less hepatic metabolism compared with omeprazole, and thus may result in less interpatient variability among slow and fast metabolizers of CYP2C19. The oral bioavailability of esomeprazole is approximately 89% with a dose of 40 mg, and the half-life is approximately 1.5 hours. Esomeprazole is effective in the healing of erosive esophagitis, with a rate of healing at week 8 of 93.7% (p < 0.001). In maintenance therapy of healed erosive esophagitis, esomeprazole maintained healing rates >90% (6-mo trial). Esomeprazole is comparable with omeprazole (both in combination with appropriate antibiotics) in the eradication of Helicobacter pylori, with eradication rates of 89.7% and 87.8%, respectively. The drug is well tolerated. The few adverse effects associated with esomeprazole are diarrhea, headache, nausea, abdominal pain, respiratory infection, and sinusitis. CONCLUSIONS: Esomeprazole is a safe and effective PPI. It is effective in the treatment of peptic ulcer disease and gastroesophageal reflux disease.     

An overview of proton pump inhibitors.

SUMMARY: Proton pump inhibitors are the standard of treatment for acid-related disorders. These disorders include gastroesophageal reflux disease and its complications (i.e., erosive esophagitis and Barrett's esophagus), peptic ulcer disease, Zollinger-Ellison syndrome, and idiopathic hypersecretion. Proton pump inhibitors are also successfully used for the treatment of Helicobacter pylori infection and upper gastrointestinal bleeding.There are currently five proton pump inhibitors approved by the Food and Drug Administration and available in the United States. These are omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix), and esomeprazole (Nexium). This review discusses the history of proton pump inhibitors and compares and evaluates the pharmacology including mechanism of action, pharmacokinetics, pharmacodynamics, administration, dosage, and drug interactions. Information regarding therapeutic indications, clinical efficacy, short- and long-term side effects, and cost is also presented. A case presentation offers an analysis of the use of proton pump inhibitors in individualized patient care.     

Clinical effect of proton pump inhibitors on reflux esophagitis]

The clinical efficacy of proton pump inhibitors (PPI, omeprazole 20 mg or lansoprazole 30 mg), once daily, after breakfast, was studied in patients with erosive/ulcerative reflux esophagitis. The following results were obtained. 1) Twenty-four hour esophageal pH monitoring was performed before treatment and on 7th day of PPI medications. Omeprazole reduced the percent time pH less than 4 from 29.1 to 1.2 and lansoprazole from 68.0 to 2.4. 2) The cumulative disappearance rate of overall symptom was 52% after 1 week and 62% after 2 weeks with omeprazole these were 66% and 91%, and with lansoprazole respectively 3) The endoscopic healing rate was 63% was after 2 weeks and 76% after 4 weeks with omeprazole medication, and 76% and 97% respectively with lansoprazole. These results indicate that PPI medication inhibits the acid reflux almost completely and is a more useful therapeutic agent for GERD than H2-antagonists.     

Proton pump inhibitors: an update

Since their introduction in the late 1980s, proton pump inhibitors have demonstrated gastric acid suppression superior to that of histamine H2-receptor blockers. Proton pump inhibitors have enabled improved treatment of various acid-peptic disorders, including gastroesophageal reflux disease, peptic ulcer disease, and nonsteroidal antiinflammatory drug-induced gastropathy. Proton pump inhibitors have minimal side effects and few significant drug interactions, and they are generally considered safe for long-term treatment. The proton pump inhibitors omeprazole, lansoprazole, rabeprazole, and the recently approved esomeprazole appear to have similar efficacy.     

Healing and relapse rates in gastroesophageal reflux disease treated with the newer proton-pump inhibitors lansoprazole, rabeprazole, and pantoprazole compared with omeprazole, ranitidine, and placebo: evidence from randomized clinical trials

BACKGROUND: The older proton pump inhibitor (PPI) omeprazole and the newer PPIs lansoprazole, rabeprazole, and pantoprazole are approved for the acute and maintenance treatment of gastroesophageal reflux disease (GERD). OBJECTIVE: On the basis of the results of randomized clinical trials, this study sought to estimate healing and relapse rates in acute and maintenance treatment of GERD with the newer PPIs compared with omeprazole, the histamine2-receptor antagonist ranitidine (the most frequent non-PPI comparator in studies of PPIs), and placebo. METHODS: A search of MEDLINE was conducted to identify randomized, controlled clinical trials that included a PPI in > or =1 treatment arm and assessed the healing of erosive esophagitis endoscopically. The primary outcome for studies of acute therapy was healing rate, and the primary outcome for studies of maintenance therapy was relapse rate. RESULTS: Fifty-three studies were identified, of which 38 involved acute therapy (12 excluded) and 15 maintenance therapy. None of the studies of pantoprazole met the inclusion criteria for maintenance therapy. The 8-week overall healing rate ratios in the comparison of newer PPIs with omeprazole 20 mg/d were as follows: lansoprazole 30 mg/d, 1.02 (95% CI, 0.98-1.06): rabeprazole 20 mg/d, 0.93 (95% CI, 0.87-1.00); and pantoprazole 40 mg/d, 0.98 (95% CI, 0.90-1.07). In the comparison of any PPI with ranitidine 300 mg/d, the ratios were as follows: lansoprazole, 1.62 (95% CI, 1.46-1.76); rabeprazole, 1.36 (95% CI, 1.20-1.54); pantoprazole, 1.60 (95% CI, 1.33-1.96); and omeprazole, 1.58 (95% CI, 1.41-1.78). Relapse rates over 1 year of treatment were similar between lansoprazole and rabeprazole. Compared with ranitidine, there were statistically significant differences in the rates of resolution of heartburn symptoms (P < 0.002), ulcer healing (P < 0.05), and relapse (P < 0.01). Similar results were seen in the comparison of PPIs with placebo in terms of rates of resolution of heartburn symptoms (P < 0.01), ulcer healing (P < 0.001), and relapse (P < 0.006). CONCLUSIONS: In this study, the newer PPIs were of similar efficacy to omeprazole in terms of heartburn control, healing rates, and relapse rates. All the PPIs were superior to ranitidine and placebo in healing erosive esophagitis and decreasing relapse rates.     

Recent effectiveness of proton pump inhibitors for severe reflux esophagitis: the first multicenter prospective study in Japan

Proton pump inhibitors are the first-line treatment for reflux esophagitis. Because severe reflux esophagitis has very low prevalence in Japan, little is known about the effectiveness of proton pump inhibitors in these patients. This prospective multicenter study assessed the effectiveness of proton pump inhibitors for severe reflux esophagitis in Japan. Patients with modified Los Angeles grade C or D reflux esophagitis were treated with daily omeprazole (10 or 20 mg), lansoprazole (15 or 30 mg), or rabeprazole (10, 20, or 40 mg) for 8 weeks. Healing was assessed endoscopically, with questionnaires administered before and after treatment to measure the extent of reflux and dyspepsia symptoms. Factors affecting healing rates, including patient characteristics and endoscopic findings, were analyzed. Of the 115 patients enrolled, 64 with grade C and 19 with grade D reflux esophagitis completed the study. The healing rate was 67.5% (56/83), with 15 of the other 27 patients (55.6%) improving to grade A or B. No patient characteristic or endoscopic comorbidity was significantly associated with healing rate. Reflux and dyspepsia symptoms improved significantly with treatment. The low healing rate suggests the need of endoscopic examination to assess healing of reflux esophagitis at the end of therapy. (UMIN000005271)     

Dexlansoprazole MR: a review

Dexlansoprazole MR is the R-enantiomer of lansoprazole that is delivered by a novel system, the dual delayed release formulation. The drug has been shown to be efficacious in healing erosive esophagitis as compared with lansoprazole. When compared to placebo, dexlansoprazole provided significantly higher maintenance rates for healed esophageal mucosa in patients with erosive esophagitis and symptom control in patients with non-erosive reflux disease. Dexlansoprazole could be taken without regard to food. Overall, dexlansoprazole is well tolerated and has a comparable side-effect profile to lansoprazole.     

埃索美拉唑与奥美拉唑对非糜烂性反流病的诊断效果比较

目的:比较埃索美拉唑与奥美拉唑对非糜烂性反流病的诊断效果,应用埃索美拉唑治疗非糜烂性反流病量效关系及其早期诊断价值。方法:将96例经胃镜检查食管无异常发现但有明显烧心、反酸、胸骨后疼痛等典型反流症状的患者随机分为3组:A组32例,给予埃索美拉唑40mg每日早晚各1次口服;B组32例,埃索美拉唑20mg每日早晚各1次口服;C组32例,予奥美拉唑40mg,每日早晚各1次口服。3组均连服4周。于用药后第1～7d及二周后,按标准对烧心、反酸、胸痛进行症状评分,并记录患者有无不良反应。每周结束后进行症状评分。结果:A组在5～7d的治疗试验阳性率与B组及C组相比,差异有统计学意义;C组与B组相比差异无统计学意义。所有试验患者均未发生明显不良反应。结论:埃索美拉唑可以安全地用于非糜烂性反流病诊断的质子泵抑制剂试验药物,且作用强、速度快,可更早显示诊断价值。与奥美拉唑两者的远期治疗效果差异无统计学意义。     

Esomeprazole in acute and maintenance treatment of reflux oesophagitis: a multicentre prospective study

INTRODUCTION: The aim of this study was to assess the efficacy and safety of esomeprazole 40 mg once daily (q.d.) in healing reflux oesophagitis at 4 and 8 weeks, and the efficacy of esomeprazole 20 mg q.d. for 12 weeks in the maintenance of remission. METHODS: A total of 235 patients with endoscopically proven reflux oesophagitis were enrolled in this study, which consisted of two phases (healing and maintenance therapy). Patients who showed complete endoscopic and symptomatic healing at the end of 4 or 8 weeks were switched to maintenance treatment with esomeprazole 20 mg q.d. for 12 weeks. The primary efficacy endpoint was healing of reflux oesophagitis at week 8. Secondary assessments included the proportion of patients with symptomatic relapse in the maintenance phase. RESULTS: At the end of week 8, 88% (95% life-table confidence intervals [CI]: 84%, 92%) of patients were healed endoscopically and 90.6% of the patients were asymptomatic. Patient age, gender and Helicobacter pylori status had no effect on the efficacy of treatment. During the 12-week maintenance treatment phase, symptomatic relapse ratios were 0.5%, 2.2%, and 0%, for the first, second, and third 4-week periods, respectively. The proportions of patients satisfied with treatment were 95% and 99.4% at the end of acute and maintenance treatment, respectively. The most common adverse effects were headache, upper respiratory tract infection and abdominal pain. CONCLUSIONS: Esomeprazole is effective in the healing of reflux oesophagitis, the resolution of heartburn, and in maintaining symptomatic remission. The effectiveness of esomeprazole in patients with gastroesophageal reflux disease is not affected by the presence of H. pylori.     

Proton pump inhibitors in the treatment of peptic ulcers resistant to H2-receptor antagonists]

The aim of this study is to evaluate the therapeutic effect of proton pump inhibitors on peptic ulcers resistant to H2-receptor antagonists. Patients with ulcers resistant to at least 3 months treatment with standard or greater doses of H2-receptor antagonists were treated with 20 mg of omeprazole or 30 mg of lansoprazole, once daily, for 2 to 8 weeks. Endoscopy was performed every 2 weeks to confirm ulcer healing. Eleven of 28 (39%) gastric ulcers healed within 4 weeks and 20 (71%) within 8 weeks with omeprazole. Eight of 19 (42%) gastric ulcers healed within 4 weeks and 14 (74%) within 8 weeks with lansoprazole. All of the duodenal ulcer healed within 6 weeks with omeprazole or lansoprazole. No adverse effects were observed in this study. These results suggest that proton pump inhibitors are highly effective in the treatment of peptic ulcer resistant to H2-receptor antagonists.     

Esomeprazole-induced healing of gastroesophageal reflux disease is unrelated to the genotype of CYP2C19: evidence from clinical and pharmacokinetic data

BACKGROUND: The clinical outcome of acid-related disorders treated by proton pump inhibitors (PPIs) might be dependent on the polymorphically expressed cytochrome P450 (CYP) 2C19, which is involved in PPI metabolism. We tested whether esomeprazole-induced healing of gastroesophageal reflux disease (GERD) is related to CYP2C19 genotype. METHODS: Two hundred five patients with GERD (Los Angeles classification grade A or B) were included in a case-control study according to endoscopic outcome (healed versus unhealed group, matched for confounders) after treatment with 40 mg esomeprazole daily for 4 weeks. The frequency of CYP2C19 genotypes was determined as the primary outcome measure for both groups. In a second trial plasma levels of esomeprazole and corresponding CYP2C19 and CYP3A4 metabolites (5-hydroxyomeprazole and omeprazole sulfone) were monitored in 10 CYP2C19 wild-type patients with GERD after the first and last doses (day 7) of 40 mg esomeprazole daily to calculate metabolic ratios. RESULTS: CYP2C19 wild-type (n = 148) and heterozygous (n = 51) or homozygous variant (n = 6) patients did not differ with respect to baseline characteristics. The frequency distribution of CYP2C19 genotypes was not different between patients with complete (75/100) and incomplete (73/105) healing (P = .65). When a single esomeprazole dose and multiple dosing were compared, the low contribution of CYP2C19 to the elimination of esomeprazole decreased further by 50%. In contrast, the CYP3A4-dependent formation of omeprazole sulfone increased by 40%, and consequently, the metabolic ratio of omeprazole sulfone to 5-hydroxyomeprazole was elevated from 7.9 to 19.3 (P = .0004). CONCLUSION: In contrast to other PPIs, esomeprazole-induced healing of GERD is unrelated to the CYP2C19 genotype, which can be explained by the metabolic shift toward the CYP3A4-mediated pathway.     

Dexlansoprazole MR – A review

Abstract

Dexlansoprazole MR is the R-enantiomer of lansoprazole that is delivered by a novel system, the dual delayed release formulation. The drug has been shown to be efficacious in healing erosive esophagitis as compared with lansoprazole. When compared to placebo, dexlansoprazole provided significantly higher maintenance rates for healed esophageal mucosa in patients with erosive esophagitis and symptom control in patients with non-erosive reflux disease. Dexlansoprazole could be taken without regard to food. Overall, dexlansoprazole is well tolerated and has a comparable side-effect profile to lansoprazole.     

Acid-suppressive effects of rabeprazole, omeprazole, and lansoprazole at reduced and standard doses: a crossover comparative study in homozygous extensive metabolizers of cytochrome P450 2C19

BACKGROUND AND OBJECTIVES: To improve clinical outcomes of the initial therapy for gastroesophageal reflux disease, intragastric pH should be above 4.0 for more than 20 hours a day (83.3%) and nocturnal gastric acid breakthrough, defined as 60 continuous minutes of intragastric pH below 4.0 at night, should be inhibited. A "step-down" therapy sometimes fails because of insufficient acid suppression. Therefore we compared the acid-suppressive effects of proton pump inhibitors. METHODS: This was a prospective, randomized, open-label, 8-way crossover study. In 9 healthy Helicobacter pylori-negative cytochrome P450 (CYP) 2C19 homozygous extensive metabolizers, intragastric pH was measured for 24 hours on day 7 of treatment with rabeprazole, omeprazole, and lansoprazole orally administered once daily at reduced and standard doses. RESULTS: Compared with baseline data (7% [range, 5%-20%]), the median values of the 24-hour percent of time that intragastric pH was above 4.0 significantly increased but did not exceed 83.3% under any of the 7 regimens, which were as follows: 10 mg rabeprazole (51% [range, 28%-78%], P < .01), 20 mg rabeprazole (59% [range, 36%-83%], P < .01), 10 mg omeprazole (26% [range, 4%-33%], P < .05), 20 mg omeprazole (48% [range, 31%-73%], P < .01), 40 mg omeprazole (62% [range, 47%-87%], P < .01), 15 mg lansoprazole (34% [range, 5%-51%], P < .05), and 30 mg lansoprazole (56% [range, 20%-76%], P < .05). Significant differences were observed among 10, 20, and 40 mg omeprazole (10 mg versus 20 mg, P < .01; 10 mg versus 40 mg, P < .01; and 20 mg versus 40 mg, P < .05) and between 15 and 30 mg lansoprazole (P < .01), whereas no significant difference was observed between 10 and 20 mg rabeprazole. Nocturnal gastric acid breakthrough was observed under all regimens. CONCLUSIONS: Rabeprazole, omeprazole, and lansoprazole, given once daily at standard doses, cannot be expected to achieve ideal acid suppression for the initial therapy for gastroesophageal reflux disease in Helicobacter-negative CYP2C19 homozygous extensive metabolizers. Rabeprazole 10 mg may be appropriate for step-down therapy.     

An overview of the success and failure of surgical therapy: standards against which the outcome of endoscopic therapy is measured

Medical therapy for reflux disease has evolved from frequent antacid use to once daily proton pump inhibitor therapy. Despite the efficacy of these agents in healing erosive esophagitis, there are several short-comings with medical therapy including incomplete symptom relief, the need for continuous maintenance therapy, and cost. Endoscopic and laparoscopic treatments for reflux disease are appealing because they could reduce or eliminate the need for chronic maintenance therapy with medications. While there is evidence of high quality on the efficacy of medical therapy from randomized controlled trials, data on endoscopic procedures and surgery is more limited. This article summarizes the needed studies and the standards against which these procedures should be measured.     

Is ranitidine therapy sufficient for healing peptic ulcers associated with non‐steroidal anti‐inflammatory drug use?

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of serious gastroduodenal events. To minimise these risks, patients often require concomitant acid-suppressive therapy. We conducted a literature review of clinical trials examining use of ranitidine 150 mg twice daily to heal gastroduodenal ulcers (GU) in NSAID recipients. Seven studies were identified. After 8 weeks' treatment with ranitidine, GU healing rates ranged from 50% to 74% and rates of duodenal ulcer (DU) healing ranged from 81% to 84%. Ranitidine was more effective when NSAIDs were discontinued (healing rates reaching 95% and 100%, respectively). The ulcer healing rate with sucralfate was similar to that of ranitidine. However, proton pump inhibitor (PPI) therapy was associated with significantly greater rates of both GU and DU healing than ranitidine; 8-week GU rates were 92% and 88% with esomeprazole 40 mg and 20 mg, respectively (vs. 74% with ranitidine, p < 0.01). For omeprazole, 8-week healing rates were 87% with omeprazole 40 mg and 84% with omeprazole 20 mg (vs. 64% for ranitidine, p < 0.001), and for lansoprazole the corresponding values were 73-74% and 66-69% for the 30 mg and 15 mg doses, respectively (vs. 50-53% for ranitidine, p < 0.05). In the PPI study reporting DU healing the values were 92% for omeprazole 20 mg (vs. 81% for ranitidine, p < 0.05) and 88% for omeprazole 40 mg (p = 0.17 vs. ranitidine). NSAID-associated GU are more likely to heal when patients receive concomitant treatment with a PPI rather than ranitidine.     

A randomised prospective study comparing the effectiveness of esomeprazole treatment strategies in clinical practice for 6 months in the management of patients with symptoms of gastroesophageal reflux disease

One option for patients with symptoms of gastroesophageal reflux disease (GERD) is treatment with proton pump inhibitors without prior endoscopy. Continuous or on-demand maintenance therapy are options for symptom-free patients. This study assessed the efficacy of three different treatment options in GERD patients in Norway. About 395 General Practitioners enrolled 2156 patients with symptoms of GERD in an open, randomised, parallel group trial. Following a 4-week symptom control phase [esomeprazole 40 mg once daily (od)], patients received either esomeprazole 20 mg od continuously or on-demand or ranitidine 150 mg twice-daily continuously for 6 months. The percentage of patients with no heartburn at the end of the study was maintained most effectively in the esomeprazole 20 mg continuous group (72.2%) and least effectively in the ranitidine group (32.5%). Significantly, more patients were completely/very satisfied with esomeprazole continuous (82.2%) and esomeprazole on-demand (75.4%) than with ranitidine continuous (33.5%) treatment (p < 0.0001). More patients were kept in remission, symptom free and were overall more satisfied with esomeprazole treatment than ranitidine.     

Lansoprazole-induced improvement of esophageal submucosal injury

The proton pumpvinhibitor, lansoprazole, is reported to have acid secretion inhibiting effect as well as anti-inflammatory effects such as inhibition of cytokine secretion from inflammatory cells. Clinically, excellent efficacy of lansoprazole is reported for not only gastric ulcer but also gastroesophageal reflux disease (GERD). Since GERD is categorized endoscopically into erosive esophagitis and non-erosive reflux disease, it is important to make accurate assessment of any improvement in the inflammatory process when using endoscopic ultrasonography (EUS) capable of visualizing the submucosal structure. We report here our experience in assessing the effect of treatment with lansoprazole on esophageal wall structure using EUS in patients with GERD. At baseline (before treatment), EUS showed abnormalities in the mucosa, submucosa and muscularis propria caused by inflammation, thickening of the entire esophageal wall and changes in the contractile properties of esophageal smooth muscles reflecting the effects of inflammation on the entire wall of the lower esophagus in reflux esophagitis regardless of whether it is erosive or endoscopically-negative. Treatment with lansoprazole resulted in normalization of esophageal wall structure and improvement of motility, suggesting that lansoprazole improves not only mucosal inflammation but also submucosal inflammation in GERD.