The percentages of patients in the SAS who reported one or more AE, SAE, ADR, or SADR were, respectively, 25.4, 0.7, 7.2, and 0.1. The percentages of patients in the SAS who had an AE leading to ...treatment or study discontinuation were 3.4 and 1, respectively. Effectiveness of Vonoprazan in proViding Complete Symptom Relief for Chinese Patients Diagnosed With RE Complete symptom relief for 7 consecutive days during first week of treatment Number of patients, n/N Percentage % (95% CI) Heartburn 114/326 35.0 (29.8, 40.4) Night-time heartburn 155/326 47.5 (42.0, 53.1) Regurgitation 99/330 30.0 (25.1, 35.3) Night-time regurgitation 142/330 43.0 (37.6, 48.6) CI, confidence interval; N, total number of patients with this symptom at baseline and with 7 consecutive days data for first week; n, subset of patients without this symptom for 7 consecutive days Author Notes *Presenter
VIEW (NCT04501627) is a multi-center, single-arm, prospective, observational study conducted to provide data on the safety and effectiveness of vonoprazan in real-world clinical practice for Chinese ...patients. At least one mild, moderate or severe AE, respectively, was reported in only 25.4%, 3.4% and 2.5% of these patients, and the system organ class breakdown is given in In the EAS, the percentage of patients without GERD-typical symptoms increased from 24% (95% CI: 16%, 35%) at baseline to 66% (95% CI: 53%, 77%) at week 4. Summary of AEs by Severity and System Organ Class in Elderly (age ≥65 years) Chinese RE Patients Severity N = 118 n (%) Patients with at least one AE Mild 30 (25.4) Moderate 4 (3.4) Severe 3 (2.5) Patients with AEs in each System Organ Class*† Gastrointestinal disorders Mild 18 (15.3) Moderate 3 (2.5) Psychiatric disorders Mild 6 (5.1) Moderate 1 (0.8) Musculoskeletal and connective tissue disorders Mild 4 (3.4) Severe 1 (0.8) Nervous system disorders Mild 4 (3.4) Infections and infestations Mild 2 (1.7) Severe 1 (0.8) Metabolism and nutrition disorders Mild 2 (1.7) Respiratory, thoracic and mediastinal disorders Mild 2 (1.7) Skin and subcutaneous tissue disorders Mild 2 (1.7) Investigations Mild 1 (0.8) Injury, poisoning and procedural complications Mild 1 (0.8) Reproductive system and breast disorders Mild 1 (0.8) Renal and urinary disorders Mild 1 (0.8) Moderate 1 (0.8) Hepatobiliary disorders Mild 1 (0.8) Eye disorders Severe 1 (0.8) Blood and lymphatic system disorders Mild 1 (0.8) Congenital, familial and genetic disorders Mild 1 (0.8) AEs = adverse events; *System organ classes are based on Medical Dictionary for Regulatory Activities (MedDRA) version 23.1 dated 01-SeP-2020 †Zero AEs were reported for elderly patients in the following SOCs: Cardiac disorders, Immune System disorders, Neoplasmsbenign, malignant, and unspecified (incl cysts and polyps).
Acid suppression is the primary therapy for erosive esophagitis (EE). Although proton pump inhibitors (PPIs) are considered as the first-line medication for EE, 10–20% of patients with Los Angeles C ...and D grade EE do not gain complete mucosal healing and symptom control despite 8-week double-dose PPI treatment. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB), which blocks the H+, K+-adenosine triphosphatase enzymes in a K+-competitive and reversible manner. Vonoprazan exhibits different pharmacological and pharmacokinetic profiles from conventional PPIs, and has a rapid, potent and sustained acid inhibitory effect. In this review, we summarized and discussed current evidence regarding the role of vonoprazan in terms of mucosal healing, maintaining remission and symptom relief for the management of EE, including the initial and maintenance treatment of EE, as well as for PPI-resistant EE patients. Safety concerns and cost-effectiveness analysis of vonoprazan were also mentioned in the article. As a potent and well-tolerated acid blocker, vonoprazan has the potential to become a novel option for the management of EE.
Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are ...promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making.
A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score.
Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety.
Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.
Although esophageal motor disorders are associated with chest pain and dysphagia, minimal data support a direct relationship between abnormal motor function and symptoms. This study investigated ...whether high-resolution manometry (HRM) metrics correlate with symptoms.
Consecutive HRM patients without previous surgery were enrolled. HRM studies included 10 supine liquid, 5 upright liquid, 2 upright viscous, and 2 upright solid swallows. All patients evaluated their esophageal symptom for each upright swallow. Symptoms were graded on a 4-point likert score (0, none; 1, mild; 2, moderate; 3, severe). The individual liquid, viscous or solid upright swallow with the maximal symptom score was selected for analysis in each patient. HRM metrics were compared between groups with and without symptoms during the upright liquid protocol and the provocative protocols separately.
A total of 269 patients recorded symptoms during the upright liquid swallows and 72 patients had a swallow symptom score of 1 or greater. Of the 269 patients, 116 recorded symptoms during viscous or solid swallows. HRM metrics were similar between swallows with and without associated symptoms in the upright, viscous, and solid swallows. No correlation was noted between HRM metrics and symptom scores among swallow types.
Esophageal symptoms are not related to abnormal motor function defined by HRM during liquid, viscous or solid bolus swallows in the upright position. Other factors beyond circular muscle contraction patterns should be explored as possible causes of symptom generation.
Erosive esophagitis (EE) is a gastroesophageal reflux disease characterized by mucosal breaks in the esophagus. Proton pump inhibitors are widely used as maintenance therapy for EE, but many patients ...still relapse. In this trial, we evaluated the noninferiority of vonoprazan vs. lansoprazole as maintenance therapy in patients with healed EE.
We performed a double-blind, double-dummy, multicenter, phase 3 clinical trial among non-Japanese Asian adults with endoscopically confirmed healed EE from April 2015 to February 2019. Patients from China, South Korea, and Malaysia were randomized to vonoprazan 10 mg or 20 mg once daily or lansoprazole 15 mg once daily for 24 weeks. The primary endpoint was endoscopically confirmed EE recurrence rate over 24 weeks with a noninferiority margin of 10% using a two-sided 95% confidence interval (CI). Treatment-emergent adverse events (TEAEs) were recorded.
Among 703 patients, EE recurrence was observed in 24/181 (13.3%) and 21/171 (12.3%) patients receiving vonoprazan 10 mg or 20 mg, respectively, and 47/184 (25.5%) patients receiving lansoprazole (differences: -12.3% 95% CI, -20.3% to -4.3% and -13.3% 95% CI, -21.3% to -5.3%, respectively), meeting the primary endpoint of noninferiority to lansoprazole in preventing EE recurrence at 24 weeks. Evidence of superiority (upper bound of 95% CI <0%) was also observed. At 12 weeks, endoscopically confirmed EE recurrence was observed in 5/18, 2/20, and 7/20 of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. TEAEs were experienced by 66.8% (157/235), 69.0% (156/226), and 65.3% (158/242) of patients receiving vonoprazan 10 mg, vonoprazan 20 mg, and lansoprazole, respectively. The most common TEAE was upper respiratory tract infection in 12.8% (30/235) and 12.8% (29/226) patients in vonoprazan 10 mg and 20 mg groups, respectively and 8.7% (21/242) patients in lansoprazole group.
Vonoprazan maintenance therapy was well-tolerated and noninferior to lansoprazole for preventing EE recurrence in Asian patients with healed EE.
https://clinicaltrials.gov; NCT02388737.
Abdominal bloating or distension (AB/D) is a common complaint in the outpatient of gastroenterology department. Since the potential contributors are numerous and complex, a longitudinal study on the ...disease spectrum and natural history of patients was performed to better understand the key factors of AB/D.
Consecutive patients with the chief complaint of AB/D referred to the outpatient clinic were screened. Functional gastrointestinal disorders (FGIDs) were diagnosed according to Rome IV criteria. A 3-year follow-up was performed to seek for the changes in symptoms as well as disease spectrum.
A total of 261 participants were enrolled and 139 completed the follow-up. Most patients suffered from moderate to severe symptoms more than 1 day per week. Common causes of AB/D were FGIDs (51.7%) and organic diseases (17.2%). The latter group was older with lower body mass index (BMI). Functional dyspepsia was the most common type of FGIDs in AB/D. The symptoms of 18.0% of participants failed to improve at the end of the 3-year follow-up, and those diagnosed with FGIDs were most likely to continue to suffer. Abdominal pain was a positive predictive factor for good prognosis in the FGIDs group. Besides, only 22.7% of participants had a consistent diagnosis of FGIDs during follow-up.
FGIDs are the most common diagnosis in patients with AB/D. Symptoms were especially hard to be improved. Classification diagnoses of FGIDs in AB/D patients fluctuated significantly over time.
Background. Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has ...been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods. This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30 mg as single dose, or 50 mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4 : 1 ratio. Results. 59 healthy volunteers received tenapanor 10 mg (n = 12 Chinese), 30 mg (n = 12 Chinese), or 50 mg (n = 12 (Chinese), n = 11 (Caucasian)) or placebo (n = 12, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50 mg) of Chinese subjects, the mean Cmax, AUC0-t, and AUC0-∞ of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The Cmax accumulation ratio was 1.55 to 6.92 after 50 mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50 mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion. Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background:
The aim of the current systematic review and network meta-analysis (NMA) was to assess the diagnostic characteristics of the gastroesophageal reflux disease questionnaire (GERDQ), ...proton-pump inhibitor (PPI) test, baseline impedance, mucosal impedance, dilated intercellular spaces (DIS), salivary pepsin, esophageal pH/pH impedance monitoring and endoscopy for gastroesophageal reflux disease (GERD).
Methods:
We searched PubMed and the Cochrane Controlled Trial Register database (from inception to 10 April 2018) for studies assessing the diagnostic characteristics of the GERDQ, PPI test, baseline impedance, mucosal impedance, DIS, or salivary pepsin and esophageal pH/pH impedance monitoring/endoscopy in patients with GERD. Direct pairwise comparison and a NMA using Bayesian methods under random effects were performed. We also assessed the ranking probability.
Results:
A total of 40 studies were identified. The NMA found no significant difference among the baseline impedance, mucosal impedance, and esophageal pH/pH impedance monitoring and endoscopy in terms of both sensitivity and specificity. It was also demonstrated that the salivary pepsin detected by the Peptest device had comparable specificity to esophageal pH/pH impedance monitoring and endoscopy. Results of ranking probability indicated that esophageal pH/pH impedance monitoring and endoscopy had highest sensitivity and specificity, followed by mucosal impedance and baseline impedance, whereas GERDQ had the lowest sensitivity and PPI test had the lowest specificity.
Conclusions:
In a systematic review and NMA of studies of patients with GERD, we found that baseline impedance and mucosal impedance have relatively high diagnostic performance, similar to esophageal pH/pH impedance monitoring and endoscopy.
There are currently no criteria for ineffective esophageal motility (IEM) and ineffective swallow (IES) in esophageal pressure topography (EPT). Our aims were to use high-resolution manometry metrics ...to define IEM within the Chicago Classification and to determine the distal contractile integral (DCI) threshold for IES.
The EPT of 150 patients with either dysphagia or reflux symptoms were reviewed. Peristaltic function in EPT was defined by the Chicago Classification; the corresponding conventional line tracing (CLT) were reviewed separately. Generalized linear mixed models were used to find thresholds for DCI corresponding to traditionally determined IES and failed swallows. An external validation sample was used to confirm these thresholds.
In terms of swallow subtypes, IES in CLT were a mixture of normal, weak, and failed peristalsis in EPT. A DCI of 450 mm Hg-s-cm was determined to be optimal in predicting IES. In the validation sample, the threshold of 450 mm Hg-s-cm showed strong agreement with CLT determination of IES (positive percent agreement 83%, negative percent agreement 90%). The patient diagnostic level agreement between CLT and EPT was good (78.6% positive percent agreement and 63.9% negative percent agreement), with negative agreement increasing to 92.0% if proximal breaks were excluded.
The manometric correlate of IEM in EPT is a mixture of failed swallows and weak swallows with breaks in the middle/distal troughs. A DCI value <450 mm Hg-s-cm can be used to predict IES previously defined in CLT. IEM can be defined by >5 swallows with weak/failed peristalsis or with a DCI <450 mm Hg-s-cm.
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