Vonoprazan prevents low-dose aspirin-associated ulcer recurrence: randomised phase 3 study.

OBJECTIVE: Compare efficacy and safety of vonoprazan and lansoprazole for secondary prevention of low-dose aspirin (LDA)-associated peptic ulcers in a 24-week study and long-term extension therapy in separate study. DESIGN: Double-blind, randomised, non-inferiority study; single-blind extension study at 104 Japanese sites, including 621 patients (439 in extension) with a history of peptic ulcers who required long-term LDA therapy. Randomised (1:1:1, computer generated) patients received lansoprazole 15 mg (n=217), vonoprazan 10 mg (n=202) or vonoprazan 20 mg (n=202) once daily for 24 weeks (double blind) and ≤2 years (extension). The following measurements were made: 24-week (primary outcome; double blind) and 12-week peptic ulcer recurrence rate, 24-week GI bleeding rate, cumulative incidences of peptic ulcer recurrence and GI bleeding, treatment-emergent adverse events, laboratory results, serum gastrin and pepsinogen I/II concentrations. RESULTS: The 24-week peptic ulcer recurrence rate was 2.8%, 0.5% and 1.5% in the lansoprazole 15 mg, vonoprazan 10 mg and vonoprazan 20 mg groups, respectively. Vonoprazan was non-inferior (Farrington and Manning test: margin 8.7%, significance level 2.5%) to lansoprazole. In the post hoc analyses of the extension study, peptic ulcer recurrence rates were significantly lower with vonoprazan 10 mg (log-rank test, P=0.039), but not vonoprazan 20 mg (P=0.260), compared with lansoprazole 15 mg. GI bleeding rates were higher with lansoprazole compared with two doses of vonoprazan in both 24-week study and extension study. CONCLUSION: Vonoprazan (10 and 20 mg) was as effective as lansoprazole (15 mg) in preventing peptic ulcer recurrence during LDA therapy, had a similar long-term safety profile and was well tolerated. TRIAL REGISTRATION NUMBERS: NCT01452763; NCT01456247.

Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study.

OBJECTIVE: To assess the non-inferiority of vonoprazan to lansoprazole for secondary prevention of non-steroidal anti-inflammatory drug (NSAID)-induced peptic ulcer (PU) and the safety of vonoprazan during extended use. DESIGN: A phase 3, 24-week, multicenter, randomised, double-blind (DB), active-controlled study, followed by a phase 3, ≥28 week, multicenter, single-blind, parallel-group extension study (EXT) in outpatients (n=642) receiving long-term NSAID therapy who are at risk of PU recurrence. The patients received vonoprazan (10 mg or 20 mg) or lansoprazole 15 mg once daily. For DB, non-inferiority of the proportion of patients with recurrent PU within 24 weeks was analysed by Farrington and Manning test (significance level 2.5%, non-inferiority margin 8.3%; primary endpoint), recurrent PU within 12 weeks, bleeding and time-to-event of PU (secondary endpoint) and treatment-emergent adverse events (TEAEs). For EXT, TEAEs (primary endpoint), recurrent PU and safety (secondary) were assessed up to 104 weeks for patients in the extension study. RESULTS: The non-inferiority of vonoprazan 10 mg and 20 mg to lansoprazole 15 mg was verified (percentage difference -2.2%,95% CI -6.2% to 1.8%, p<0.001; -2.1%,95% CI -6.1% to 2.0%, p<0.001, respectively). The proportion of patients with endoscopically confirmed recurrent PU within 24 weeks was 3.3%, 3.4% and 5.5%, for vonoprazan 10 mg, 20 mg and lansoprazole 15 mg, respectively. No significant safety concerns were identified. CONCLUSION: The non-inferiority of vonoprazan (10 and 20 mg) was verified in patients receiving long-term NSAIDs in DB; it was effective and well tolerated in EXT for longer than 1 year, with a safety profile similar to lansoprazole (15 mg). TRIAL REGISTRATION NUMBERS: NCT01452750, NCT01456260; Results.

Vonoprazan, a Novel Potassium-Competitive Acid Blocker, Should Be Used for the Helicobacter pylori Eradication Therapy as First Choice: A Large Sample Study of Vonoprazan in Real World Compared with Our Randomized Control Trial Using Second-Generation Proton Pump Inhibitors for Helicobacter pylori Eradication Therapy.

BACKGROUND/AIMS: Phase III study demonstrated that vonoprazan-based Helicobacter pylori eradication therapy achieved higher eradication rate compared with lansoprazole. However, there is no study that evaluated the efficacy of vonoprazan in a large sample in real world. We investigated the eradication rate and safety of vonoprazan-based eradication therapy compared with our randomized control trial using second-generation proton pump inhibitor (PPIs). METHODS: (First study) A total of 147 patients who have H. pylori infection were randomly assigned to receive either, esomeprazole (EPZ) group and rabeprazole (RPZ) group. (Second study) 1,688 patients who have H. pylori infection underwent primary eradication with triple therapy involving vonoprazan. In both studies, triple therapy with amoxicillin, clarithromycin, and PPI or vonoprazan was performed, and eradication effect was assessed by an urea breath test. RESULTS: (First study) Eradication rate was 77.5% in the EPZ group and 68.4% in the RPZ group; no significant difference was observed between the 2 groups. (Second study) The successful primary eradication rate was 90.8%. There was no severe adverse effect. CONCLUSIONS: The eradication rate of vonoprazan-based triple therapy was remarkably higher compared with second-generation PPIs-based triple therapy in real world. Vonoprazan is very likely to become the first option for future eradication therapy.

Exploratory Research on Latent Esophageal Motility Disorders in Dysphagia Patients.

BACKGROUND/AIMS: High-resolution manometry (HRM) has been applied to assess esophageal motility disorders. However, the frequency and types of motility disorders in patients with dysphagia, which are frequently seen in clinical practice, are not clear. We evaluated latent esophageal motility disorders associated with dysphagia. METHODS: The study included patients without erosive esophageal mucosal damage and with dysphagia symptoms refractory to at least 8 weeks of standard-dose proton pump inhibitors. After enrolment, HRM was used to evaluate for esophageal motility disorder based on the Chicago classification. RESULTS: Esophageal motility disorder was found in 58 of 100 patients and was classified based on the causes: achalasia (13%), esophagogastric junction outflow obstruction (16%), distal esophageal spasms (3%), weak peristalsis (14%), frequently failed peristalsis (5%), and hypertensive peristalsis (7%). CONCLUSION: Primary esophageal motility disorder was found in approximately 50% of cases in dysphagia patients. Therefore, esophageal motility disorder is not an uncommon condition and should be sought for in order to elucidate precisely the cause of dysphagia.

Albumin and apolipoprotein H mRNAs in human plasma as potential clinical biomarkers of liver injury: analyses of plasma liver-specific mRNAs in patients with liver injury.

CONTEXT: Plasma liver-specific mRNAs are useful biomarkers of hepatotoxicity in rats. OBJECTIVE: To investigate the potential application of liver-specific mRNAs as biomarkers for liver injury in humans. METHODS: We determined the plasma levels of liver-specific mRNAs by real-time qRT-PCR in healthy donors and patients with liver injury. RESULTS: Plasma levels of albumin (ALB) and apolipoprotein H (APOH) mRNAs increased in patients with elevated serum alanine aminotransferase. These mRNAs also increased in plasma after transcatheter arterial chemoembolization, which induces specific injury to liver. CONCLUSIONS: We demonstrated the potential application of plasma ALB and APOH mRNAs as clinical biomarkers for liver injury.

Evaluation of the Efficacy and Safety of Vonoprazan in Patients with Nonerosive Gastroesophageal Reflux Disease: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study.

BACKGROUND: For many patients, current treatments do not adequately resolve heartburn in nonerosive reflux disease (NERD). OBJECTIVE: To compare vonoprazan and placebo with respect to the frequency and severity of heartburn in patients with NERD. METHODS: This Phase III, double-blind, placebo-controlled, parallel-group, multicenter study included patients in Japan aged ≥20 years with Grade N or M NERD and recurrent acid reflux symptoms. Patients were blinded and randomized 1:1:1 to receive placebo or vonoprazan 10 mg or 20 mg. The primary efficacy outcome was the proportion of days without heartburn measured by patient scores during the 4-week treatment period. RESULTS: Eight hundred twenty-seven patients were randomized (placebo: n = 278, vonoprazan 10 mg: n = 278, and vonoprazan 20 mg: n = 271). Median proportion of days without heartburn was 7.4% (placebo), 10.3% (vonoprazan 10 mg), and 12.0% (vonoprazan 20 mg). Proportion of days without heartburn was not statistically significant between the vonoprazan and placebo groups (P = 0.2310 [10 mg] and P = 0.0504 [20 mg]). Mean severity of heartburn was significantly higher with placebo (median score = 1.070) than with vonoprazan 10 mg (median score = 0.990; P = 0.0440) and 20 mg (median score = 0.960; P = 0.0139). Patients whose symptoms improved at Week 2 experienced significantly increased proportion of days without heartburn and reduced mean severity of heartburn at Week 4 with vonoprazan compared with placebo (proportion of days without heartburn: P = 0.0004 [10 mg] and P = 0.0001 [20 mg] and mean severity: P < 0.0001 [10 mg] and P < 0.0001 [20 mg]). A significant difference in median proportion of days without heartburn was observed for vonoprazan 20 mg compared with placebo in patients with Grade M NERD. Incidence of treatment-emergent adverse events was 32.7% (placebo), 27.7% (vonoprazan 10 mg), and 28.0% (vonoprazan 20 mg). CONCLUSIONS: Vonoprazan at doses of 10 mg and 20 mg are not superior to placebo with respect to proportion of days without heartburn, whereas the mean severity of heartburn is lower with vonoprazan compared with placebo in patients with NERD. ClinicalTrials.gov identifier: NCT01474369.

Therapeutic effect of intensive granulocyte and monocyte adsorption apheresis combined with thiopurines for steroid- and biologics-naïve Japanese patients with early-diagnosed Crohn's disease.

BACKGROUND: Early induction with biologics can reduce complications in patients with Crohn's disease (CD) and improve their quality of life. The safety of biologics, however, is uncertain. Granulocyte and monocyte adsorptive apheresis (GMAA) is a natural biologic therapy that selectively removes granulocytes and monocytes/macrophages and has few severe adverse effects. The effects of GMAA on patients with early-diagnosed CD are unclear. We investigated the effects of GMAA combined with thiopurines on patients with early-diagnosed CD. METHODS: Twenty-two corticosteroid- and biologic-naïve patients with active early-diagnosed CD were treated with intensive GMAA (twice per week) combined with thiopurines administration. Active early-diagnosed CD was defined as follows: (i) within 2years after diagnosis of CD, (ii) with no history of both surgical treatment and endoscopic dilation therapy, and (iii) Crohn's Disease Activity Index (CDAI) was higher than 200. We investigated the ratios of clinical remission defined as CDAI was less than or equal to 150 at 2, 4, 6 and 52weeks and mucosal healing defined as a Simplified Endoscopic Activity Score for Crohn's Disease (SES-CD) as 0 at 6 and 52weeks. Adverse events were recorded at each visit. RESULTS: The ratios of clinical remission at 2, 4, and 6 weeks were 6 of 22 (27.2%), 12 of 22 (54.5%), and 17 of 22 (77.2%), respectively. At 52 weeks, 18 of 21 patients (81.8%) were in clinical remission. The ratios of mucosal healing at 6 and 52 weeks were 5 of 22 (22.7%) and 11 of 22 (50%), respectively. The difference in the mucosal healing ratio was significant between 6 and 52 weeks (p = 0.044). No serious adverse effects were observed during this study. CONCLUSIONS: Combination therapy with intensive GMAA and thiopurines administration rapidly induced high remission in patients with active early-diagnosed CD without serious adverse effect. Mucosal healing was observed in 50.0% of enrolled patients. This combination therapy might be a rational option for patients with early-diagnosed CD.

Sleep disturbances and refractory gastroesophageal reflux disease symptoms in patients receiving once-daily proton pump inhibitors and efficacy of twice-daily rabeprazole treatment.

BACKGROUND: Nighttime acid reflux that influences refractory symptoms is strongly associated with sleep disturbances. The aim of this study was to examine the associations between sleep disturbances and refractory gastroesophageal reflux disease (GERD) symptoms in patients receiving once daily proton pump inhibitors (PPI) and the efficacy of twice-daily rabeprazole treatment. METHOD: In a multicenter survey, 433 GERD patients receiving once-daily PPI treatment completed a self-report questionnaire that included the Frequency Scale for the Symptoms of GERD (FSSG) and questions about sleep disturbances. Study cases were defined as patients with an FSSG score ≥8. Of the 222 study cases, 106 individuals received rabeprazole 10 mg twice daily for 4-8 weeks. RESULTS: Of the 433 subjects, 222 patients revealed FSSG scores of ≥8. Use of a half dose of PPI was associated with such cases. PPI-refractory symptoms were found in 46% of patients with standard-dose PPI treatment. Nighttime symptoms (OR = 2.56), daytime sleepiness (OR = 1.64), and poorer sleep quality (OR = 1.67) were significantly associated with refractory GERD symptoms. Twice-daily rabeprazole treatment significantly improved FSSG scores and sleep disturbances. CONCLUSION: About half of the GERD patients receiving once-daily standard-dose PPI treatment had refractory GERD symptoms. Sleep disturbances were significantly associated with refractory GERD symptoms. Twice-daily rabeprazole treatment was effective in such cases.

Predictive factors associated with the success of pneumatic dilatation in Japanese patients with primary achalasia: a study using high-resolution manometry.

BACKGROUND/AIMS: A new classification of achalasia using high-resolution manometry (HRM) has recently been suggested. Pneumatic dilatation (PD) is a common treatment for primary achalasia. The usefulness of the new classification and HRM for the treatment and follow-up of patients after PD is unknown. The aim of this study was to evaluate the PD effectiveness and the predictive factors of success in Japanese patients with achalasia using HRM and the new classification of achalasia. METHODS: Twenty-five patients were diagnosed with primary achalasia using HRM and treated by PD in our hospital. We evaluated symptom scores and esophageal manometry 6 and 12 months after the first PD. RESULTS: After the first PD treatment, remission occurred in 24 out of 25 (96.0%) patients at 6 months and in 19 out of 25 (76.0%) patients at 12 months. With the new classification of achalasia, the success rates were 83.3, 80.0 and 50% for types I, II and III, respectively, 12 months after PD. The median age of the successful group was significantly greater than that of the failure group (47.1 vs. 37.0 years, p < 0.05). The median residual lower esophageal sphincter (LES) pressure 6 months after PD in the successful group was significantly lower than that of the failure group (9.0 vs. 15.5 mm Hg, p < 0.05). CONCLUSION: Good predictors of PD success were old age (>40 years) and residual LES pressures less than 15 mm Hg 6 months after PD.

Endoscopic evaluation of low-dose aspirin-induced gastric and duodenal ulcers during prophylaxis with lansoprazole.

BACKGROUND/AIMS: To compare the endoscopic features of LDA-induced ulcers developing during secondary prophylaxis with lansoprazole (LPZ) and gefarnate (GFN). METHODOLOGY: All ulcers that had developed during prophylaxis with LPZ (15mg once daily) and GFN (50mg twice daily) in a prospective, randomized, double-blind trial, were reviewed and compared by a panel of expert endoscopists, based on endoscopic images available from the trial, to provide evidence for efficacy of LPZ versus GFN in secondary prophylaxis in patients with endoscopically confirmed ulcer scars. RESULTS: A total of 6 and 53 patients had developed gastric or duodenal ulcers during prophylaxis with LPZ and GFN, respectively. Six gastric ulcers seen in those given LPZ were "small" and "shallow", while, of the 38 gastric ulcers seen those given GFN, 44.7% and 55.3% were "medium" or "large" and "small", respectively. Ulcers associated with blood coagula were seen only in those given GFN. Duodenal ulcers developed in 15 and 0 patients given GFN and LPZ, respectively. CONCLUSIONS: The ulcers developing during prophylaxis with GFN and LPZ varied in their features. The study findings may be useful when devising a strategy for prophylaxis of ulcers in high-risk patients receiving LDA therapy in a routine clinical setting.

Acid-suppressive effect of rabeprazole 5 mg and 10 mg once daily by 24-hour esophageal pH monitoring in patients with non-erosive reflux disease in Japan: a multicenter, randomized, parallel-group, double-blind pharmacodynamic study.

BACKGROUND: Acid suppression induced by rabeprazole 5 mg in patients with NERD has not been reported in the literature. AIMS: The objective of this study was to investigate gastroesophageal acid suppression in NERD patients by rabeprazole 5 mg and 10 mg/day. METHODS: Subjects were grade M (minimal changes) NERD patients. Twenty-two patients not responding to open label antacid therapy entered a double-blind treatment phase in which rabeprazole 5 mg or 10 mg/day for four weeks were compared. Twenty-four-hour esophageal pH monitoring was performed before and on treatment (at week 4) to assess the pharmacodynamic effect of these doses of rabeprazole. RESULTS: The frequency of heartburn episodes and the number of acid reflux episodes in the esophagus corresponded well in grade M NERD patients (r=0.44, P=0.042). Median percentage of time at pH<4 was 4.3% before treatment and 1.1% on treatment with rabeprazole 5 mg (change from baseline; -2.5%), whereas the median percentage of time at pH<4 in the rabeprazole 10 mg group was 7.4% before treatment and 0.5% on treatment (change from baseline; -6.6%). Likewise, treatment-related changes of median number of reflux episodes were -18.0 with rabeprazole 5 mg and -44.0 with rabeprazole 10 mg. For each esophageal pH data, no significant differences were observed between the two groups (P=0.377, P=0.077). CONCLUSIONS: Administration of 5 mg and 10 mg rabeprazole sufficiently inhibited pathological gastroesophageal acid reflux and relieved heartburn episodes in NERD patients who did not respond to an antacid. Further investigation would be necessary to determine proper usage of the two doses.

[Diagnosis of gastric ulcer in the elderly].

It is well known that gastric ulcers are most often found at anglus and upper corpus in the elderly. The number of gastric ulcer found at upper corpus hold half of all cases in the elderly patients with bleeding ulcer. Sixty percent of the elderly patients with bleeding ulcer took NSAIDs including low-dose aspirin in authors' hospital. Now it is easy to treat and cure bleeding ulcers due to development of endoscopic hemostasis and antiulcer drugs such as proton pump inhibitor(PPI). However, the elderly patients sometimes result in fatal outcome on bleeding from gastric ulcer. Therefore, it is important to prevent ulcer complications by PPI for the high-risk group such as elderly patients taking NSAIDs.

The impact of lifestyle modification on the health-related quality of life of patients with reflux esophagitis receiving treatment with a proton pump inhibitor.

OBJECTIVES: Although lifestyle modification involving diet, exercise, cessation of smoking, etc. is generally advised for patients with reflux esophagitis (RE), few data that show its clinical benefits are available. We analyzed whether lifestyle modification improves health-related quality of life (HRQOL) in Japanese patients with RE receiving the proton pump inhibitor (PPI) lansoprazole as a post hoc analysis of an observational study that investigated the effect of lansoprazole on HRQOL. METHODS: Patients with RE received lansoprazole for 8 weeks. HRQOL was assessed using the 8-Item Short-Form Health Survey (SF-8) and RE-specific HRQOL questionnaires at baseline and after 4 and 8 weeks of treatment. Physical and mental component summaries (PCS, MCS) and RE-specific summary (RES) scores were calculated. RESULTS: Of the 8,757 patients analyzed, 40.8% were advised regarding new lifestyle at the start of lansoprazole treatment (Group A), 33.3% were advised to continue the lifestyle as advised previously (Group B), and 25.9% did not receive any advice (Group C). The change in PCS from baseline at week 8 for Group A was 5.7 +/- 8.1, and this was significantly greater (P < 0.001) than the increases achieved in Groups B (4.3 +/- 7.5) and C (4.0 +/- 7.6). The changes in MCS and RES were also significantly greater in Group A than in the other groups. The changes in HRQOL scores from baseline were significantly greater in Group A than in the other groups, irrespective of baseline patient characteristics. CONCLUSIONS: Lifestyle modification may be clinically beneficial in terms of improving HRQOL in Japanese patients with RE who are receiving treatment with a PPI.

Efficacy of the 5-HT1A agonist tandospirone citrate in improving symptoms of patients with functional dyspepsia: a randomized controlled trial.

OBJECTIVES: Functional dyspepsia (FD) is a common condition in the general population; however, its treatment remains a challenge. The aim of this study was to examine the efficacy of tandospirone citrate, a new partial agonist of the 5-hydroxytryptamine 1A (5-HT1A) receptor, in improving the symptoms of patients with FD. METHODS: In this double-blind, placebo-controlled, multicenter study, FD patients were randomized to treatment with 10 mg t.i.d. tandospirone citrate or to placebo for 4 weeks. The primary end point was change in abdominal symptom scores. The difference in the proportion of responders (a total abdominal symptom score of 0 or 1) was also assessed. The quality-of-life questionnaire, the SF-8, and a psychological test questionnaire, the State-Trait Anxiety Inventory (STAI), were completed at baseline and at weekly intervals. RESULTS: Data were available for 144 patients: 73 for tandospirone and 71 for placebo. Improvements in total abdominal scores were significantly larger with tandospirone than placebo at weeks 1, 2, and 4. Significantly greater improvements in the tandospirone group were observed in upper abdominal pain (P=0.02) and discomfort (P=0.002) at week 4. The proportion of responders was significantly greater in the active treatment arm at weeks 3 (P=0.017) and 4 (P=0.0016). Significant improvements in STAI (P<0.0001) were reported in both arms, as well as in the majority of questions in the SF-8 (P=0.04). No serious adverse events were reported, with similar rates in both study arms. CONCLUSIONS: Despite a considerable placebo effect, the benefits of tandospirone were shown in terms of improvement in abdominal symptom scores.

Characteristics affecting health-related quality of life (HRQOL) in Japanese patients with reflux oesophagitis and the effect of lansoprazole on HRQOL.

OBJECTIVES: A survey of health-related quality of life (HRQOL) in the Japanese general population has suggested that HRQOL is affected by sex and age. We investigated whether there is any effect of baseline patients' characteristics on HRQOL of patients with reflux oesophagitis (RE), and its changes with lansoprazole (LPZ) treatment. RESEARCH DESIGN AND METHODS: This was a post hoc analysis of an open-label, multicentre, post-marketing, observational study which investigated the effect of LPZ (15 or 30 mg/day for 8 weeks) on HRQOL in patients with RE. At baseline, and after 4 and 8 weeks of treatment, HRQOL was assessed using a Japanese version of the 8-item Short-Form Health Survey (SF-8) and a newly-developed RE-specific questionnaire (RESQ). Stratified analysis of changes in HRQOL scores according to baseline patient characteristics such as sex, age and baseline severity of typical RE symptoms was performed. RESULTS: A total of 8,757 patients were included in the efficacy analysis. At baseline, physical component summary scores from the SF-8 were lower in older patients (>/=60 years) than in younger patients (<60 years), and mental component summary scores were lower in younger patients than in older patients. These scores significantly improved after LPZ treatment regardless of sex and age. HRQOL scores were lower in patients with more severe typical RE symptoms at baseline. After LPZ treatment, HRQOL scores significantly improved to similar levels irrespective of the severity of the typical RE symptom at baseline. CONCLUSIONS: This post hoc analysis suggests that sex, age and severity of typical RE symptoms affect HRQOL in patients with RE in Japan, and such factors do not affect the improvement of HRQOL with LPZ treatment. The present study suggests a positive impact of LPZ; however, it is difficult to estimate the degree of improvement in HRQOL that may have arisen from symptomatic relief as part of the natural history of the disease from the study. Our results may overestimate the efficacy of LPZ. Further well-controlled clinical studies are needed to confirm the efficacy of LPZ on HRQOL in patients with RE.

The safety and effectiveness of vonoprazan-based Helicobacter pylori eradication therapy; a prospective post-marketing surveillance.

Background: The safety and effectiveness of vonoprazan-based Helicobacter pylori (H. pylori) eradication therapy in routine clinical practice, and patient characteristics that influence safety and effectiveness, have not been well investigated.Methods: H. pylori-positive patients with gastric ulcer, duodenal ulcer, idiopathic thrombocytopenic purpura, history of endoscopic treatment of early gastric cancer, and gastritis were enrolled. Patients received vonoprazan 20 mg, amoxicillin (AMPC) 750 mg, and clarithromycin (CAM) 200-400 mg twice daily for 7 days for the first-line eradication. For the second-line eradication, vonoprazan, AMPC, and metronidazole (MTZ) 250 mg were administered. The incidence of adverse drug reactions (ADRs) and eradication rates were evaluated.Results: The incidences of ADRs with vonoprazan/AMPC/CAM and vonoprazan/AMPC/MTZ were 3.22% (16/497) and 1.89% (1/53), respectively. Commonly reported ADRs were diarrhea, nausea, dysgeusia, feces soft, and rash. The eradication rates of the first-line therapy and the second-line therapy were 91.24% (427/468) and 95.45% (42/44), respectively. No notable differences in ADRs and eradication rates were observed when stratified by patient demographic characteristics.Conclusion: No new safety concerns were observed, and the effectiveness of vonoprazan-based triple therapy was confirmed in routine clinical practice.Trial registration: This study is registered at the Japan Pharmaceutical Information Center Clinical Trials Information (JapicCTI-153003).

Efficacy and Safety of Vonoprazan in Patients With Nonerosive Gastroesophageal Reflux Disease: A Randomized, Placebo-Controlled, Phase 3 Study.

OBJECTIVES: To assess the efficacy and safety of vonoprazan on heartburn symptoms in patients with nonerosive reflux disease (NERD) (ClinicalTrials.gov: NCT02954848). METHODS: This phase 3, double-blind, placebo-controlled study included Japanese patients aged 20 years and older with grade N/M NERD and recurrent heartburn. Patients received placebo (n = 245) or vonoprazan 10 mg (n = 238) for 4 weeks. The primary efficacy outcome was frequency of heartburn experienced by patients during the treatment period (proportion of days without heartburn). Other outcomes included cumulative improvement rates of heartburn, proportion of patients with complete heartburn resolution in the fourth week of treatment, and safety. RESULTS: Compared with placebo, the proportion of days without heartburn was not significantly higher in the vonoprazan group in the full analysis (primary end point, 72.55% vs 61.50%, vonoprazan vs placebo, P = 0.0643) but was significantly higher in the per-protocol-set sensitivity analysis (P = 0.0341). Early onset of response and significantly greater cumulative improvement rates of heartburn were observed in the vonoprazan group (P = 0.0003). In a post hoc analysis, a greater proportion of patients with complete heartburn resolution in the fourth week of treatment were reported in the vonoprazan group (P = 0.0023). Incidence of treatment-emergent adverse events was similar between treatment groups (23.5% vs 23.3%); most treatment-emergent adverse events were mild in severity. DISCUSSION: Although vonoprazan 10 mg was not superior to placebo with respect to proportion of days without heartburn in Japanese patients with NERD, vonoprazan had a significantly higher cumulative rate of heartburn resolution and was well tolerated.

The demographic characteristics and health-related quality of life in a large cohort of reflux esophagitis patients in Japan with reference to the effect of lansoprazole: the REQUEST study.

BACKGROUND: Patients with reflux esophagitis (RE) in Western countries have impaired health-related quality of life (HRQOL). However, few data are available concerning HRQOL in Asian patients with RE. AIM: To determine the demographic characteristics, HRQOL, and the impact of lansoprazole treatment in a large cohort of RE patients in Japan. METHODS: Patients with RE were enrolled. Lansoprazole was administered for 8 weeks and HRQOL assessed using the SF-8 and a newly developed questionnaire for RE-specific HRQOL (RESQ) at baseline and after 4 and 8 weeks of treatment. RESULTS: Among enrolled patients, 2320 patients with the Los Angeles classification grade A to D esophagitis at enrollment to the study were analyzed. A higher proportion of older women was observed (in the group of patients aged >or=60 years, 61.3% were women). Prevalence of obesity was 4.7%. At baseline, HRQOL scores of RE patients were well below the mean for the Japanese general population in all domains of the SF-8. After 8 weeks of treatment with lansoprazole, these scores significantly improved to the levels of the general population (P < 0.01). Scores of RESQ also significantly improved (P < 0.01). CONCLUSIONS: Demographically, RE patients in Japan differ from those in Western countries with an increased proportion in older women and lower prevalence of obesity. RE has a marked negative impact on HRQOL, which is significantly improved by treatment with lansoprazole.

Obesity as a risk factor for GERD in Japan.

BACKGROUND: In Europe and the United States, it is known that obesity, which is increasing, is closely associated with gastroesophageal reflux disease (GERD), but in Japan no definite consensus has been reached on this relationship. Clarification of the relationship between the two is an important issue. METHODS: After screening, gastrointestinal endoscopic examinations were conducted on 1813 subjects who were surveyed using a questionnaire in which they recorded body weight, height, weight loss or gain, chief complaints, and underlying disease to prospectively examine the relationship between obesity and GERD. Differences in GERD prevalence and esophageal hiatal hernia prevalence in thin (body mass index less than 18.5 kg/m2), normal (18.5 to 25.0), and obese (greater than 25.0) subjects were examined, and the differences in GERD prevalence in patients with weight loss or gain were also investigated. RESULTS: GERD prevalence was 20.96% in the thin group, 24.42% in the normal group, and 31.86% in the obese group, indicating a significantly higher prevalence in the obese group compared with the other groups. The prevalence of hernia was also significantly higher in the obese group. GERD prevalence in the weight gain group was significantly higher than in the unchanged weight group and weight loss group. CONCLUSIONS: Both GERD prevalence and the prevalence of hernia were significantly higher in obese subjects, and the prevalence of GERD in subjects who had gained weight was also significantly higher. From these results, it was concluded that obesity is a risk factor for GERD in Japan.

Maintenance for healed erosive esophagitis: Phase III comparison of vonoprazan with lansoprazole.

AIM: To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis (EE). METHODS: A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg (n = 201), vonoprazan 10 mg (n = 202), or vonoprazan 20 mg (n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events (AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen I/II levels, and gastric mucosa histopathology results. RESULTS: Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg (P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg (5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan (P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively. CONCLUSION: Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.