linaprazan and Gastroesophageal-Reflux

Proton pump inhibitors (PPIs) are currently the most effective and most widely used agents for gastroesophageal reflux disease (GERD). Despite the efficacy of these agents in healing and symptom relief, a substantial proportion of patients require twice-daily therapy with PPIs, and break-through symptoms cause others to use over-the-counter antacids and histamine 2-receptor antagonists to supplement their PPI therapy. Major strategies that are being pursued include the development of agents that have a faster onset of action for on-demand therapy; have better control of acid secretion, resulting in improved healing in advanced grades of esophagitis and better symptom control; and agents that decrease transient lower esophageal sphincter relaxations (TLESRs), thereby reducing distal acid exposure and weakly acidic refluxate. A number of new pharmaceutical agents are currently undergoing clinical evaluation for the treatment of GERD. These include agents that reduce TLESRs, serotonergic agents/ prokinetics, long-acting PPIs, mucosal protectants, and antigastrin agents. One or more of these agents may be the future of GERD therapy.

Topics: Anti-Ulcer Agents; Benzamides; Cisapride; Esophageal Sphincter, Lower; Gastroesophageal Reflux; Humans; Imidazoles; Proton Pump Inhibitors; Pyridines; Quinuclidines; Serotonin 5-HT4 Receptor Agonists

Proton-pump inhibitors remain the most effective treatment for relieving symptoms, healing lesions and preventing recurrences of gastroesophageal reflux (GER). Drugs inhibiting transient relaxation of the lower esophageal sphincter have an unfavorable benefit/risk ratio. Endoscopic methods developed in recent years have not been shown effective in trials versus sham procedures. Surgical treatment is effective in GER but causes frequent uncomfortable side effects that are difficult to treat.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents; Catheter Ablation; Cisapride; Endoscopy; Enzyme Inhibitors; Fundoplication; Gastroesophageal Reflux; Gastrointestinal Agents; Humans; Imidazoles; Lansoprazole; Laparotomy; Omeprazole; Proton Pump Inhibitors; Pyridines; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Time Factors

AZD0865 is a gastric acid-suppressing agent that has a rapid onset of action and long duration of effect. This double-blind, randomized, multicenter study investigated the efficacy and safety of AZD0865 in the treatment of patients with nonerosive reflux disease (NERD).. Patients with troublesome heartburn for at least 6 months and no evidence of erosions at endoscopy were randomized to receive AZD0865 (25, 50, or 75 mg/day) or esomeprazole 20 mg/day, for 4 wk. Throughout the treatment period, patients reported the presence and intensity of heartburn and other NERD symptoms twice daily using an electronic diary. Twenty-four-hour ambulatory intraesophageal/intragastric pH monitoring was performed in a subset of patients on day 14.. A total of 1,469 patients were randomized. The median time to sustained absence of heartburn (for 7 consecutive days) was approximately 12 days for all treatment groups and did not differ significantly for any of the AZD0865 doses or compared with esomeprazole. There were no significant differences among treatment groups in the cumulative incidence of sustained absence of heartburn during 4 wk treatment (i.e., 65-70%). The percentage of time for which intragastric pH was greater than 4 was significantly greater for AZD0865 75 mg/day compared with esomeprazole 20 mg (75% vs 60%, P < 0.05). AZD0865 was generally well tolerated although reversible elevations of liver transaminases occurred in some patients receiving the agent.. AZD0865 did not provide clinical benefit over esomeprazole 20 mg in the management of patients with NERD.

Topics: Administration, Oral; Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Endoscopy, Gastrointestinal; Enzyme Inhibitors; Esomeprazole; Esophagus; Female; Follow-Up Studies; Gastric Acidity Determination; Gastroesophageal Reflux; Heartburn; Humans; Hydrogen-Ion Concentration; Imidazoles; Male; Middle Aged; Pyridines; Retrospective Studies; Severity of Illness Index; Surveys and Questionnaires; Treatment Outcome

Limited data exist on the impact of regurgitation on health-related quality of life (HRQOL) in gastro-oesophageal reflux disease (GORD). We assessed the relationship between regurgitation frequency and HRQOL before and after acid suppression therapy in GORD.. We used data from two randomised trials of AZD0865 25-75 mg/day versus esomeprazole 20 or 40 mg/day in non-erosive reflux disease (NERD) (n=1415) or reflux oesophagitis (RO) (n=1460). The Reflux Disease Questionnaire was used to select patients with frequent and intense heartburn for inclusion and to assess treatment response. The Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire was used to assess HRQOL.. At baseline, 93% of patients in both the NERD and RO groups experienced regurgitation. Mean QOLRAD scores were similar for NERD and RO at baseline and at week 4 and disclosed decremental HRQOL with increasing frequency of regurgitation; a clinically relevant difference of >0.5 in mean QOLRAD scores was seen with regurgitation ≥4 days/week versus <4 days/week. The prevalence of frequent, persistent regurgitation (≥4 days/week) at week 4 among heartburn responders (≤1 day/week of mild heartburn) was 28% in NERD and 23% in RO. QOLRAD scores were higher among heartburn responders. There was a similar pattern of impact related to regurgitation frequency in heartburn responders compared with the group as a whole.. Frequent regurgitation was associated with a clinically relevant, incremental decline in HRQOL beyond that associated with heartburn before and after potent acid suppression in both NERD and RO.. NCT00206284 and NCT00206245.

Topics: Antacids; Drug Administration Schedule; Esomeprazole; Esophagitis, Peptic; Follow-Up Studies; Gastroesophageal Reflux; Heartburn; Humans; Imidazoles; Proton Pump Inhibitors; Pyridines; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome

Although most patients with gastroesophageal reflux disease (GERD) achieve substantial symptom relief with acid suppression, many have some residual symptoms. We evaluated the responsiveness of regurgitation, characterized by the reflux disease questionnaire (RDQ) to potent acid suppression.. We analyzed data from 2 randomized controlled trials of AZD0865 (a potassium-competitive acid blocker) 25-75 mg/day vs esomeprazole 20-40 mg/day for the treatment of nonerosive reflux disease (NERD, n = 1460) or reflux esophagitis (RE, n = 1514). Inclusion criteria for both studies were high-severity substernal burning (≥4 days per week of at least moderate intensity) during the week before enrollment. Pooled data from all treatment arms were used to ascertain the response of the reflux disease questionnaire regurgitation items to potent acid suppression during the fourth week of treatment.. When the study began, 93% of patients with NERD or RE had either "acid taste in the mouth" (regurgitation-taste) or "unpleasant movement of material upwards from the stomach" (regurgitation-movement). Either or both symptoms were present and severe in 53% of NERD (n = 717) and 54% of RE patients (n = 751) for the main study outcome. During week 4 of therapy, patients with severe "regurgitation-taste" and "regurgitation-movement" responded significantly less well than patients with NERD and high severity "substernal burning" (34% and 26% vs 49%) or those with RE (44% and 33% vs 55%). There were no differences in symptom response between patients with healed and nonhealed RE.. Regurgitation was less responsive to acid suppression than heartburn in patients with gastroesophageal reflux disease, indicating that persistent regurgitation is a common cause of incomplete treatment response.

Topics: Anti-Ulcer Agents; Esomeprazole; Gastroesophageal Reflux; Heartburn; Humans; Imidazoles; Laryngopharyngeal Reflux; Pyridines; Randomized Controlled Trials as Topic; Treatment Outcome