vonoprazan and Duodenal-Ulcer

Helicobacter pylori induces chronic gastritis and duodenal ulcer in a small fraction of the colonised population. Three decades after the discovery of H. pylori and disclosure of an urgent need for eliminating the bacterium in patients, it seems that we are still in the first steps of dealing with this mysterious organism. Treatment of H. pylori is a complex dilemma for clinicians, a repeating sentence by many scientists who spend years on this research topic. Apart from many modifications in initial first-line treatment of H. pylori, gastroenterologists are unable to overcome the problem of therapeutic failure. Choosing the best regimen in any region depends on many factors, which have been the focus of many randomised clinical trials. A potential increase in efficacy of future therapies may be influenced by adding the novel potassium-competitive acid blocker vonoprazan. Undeniably, in-depth analysis is necessary to propose more effective therapeutic regimens. Meanwhile, we recommend the performance of antimicrobial susceptibility testing before any antimicrobial prescription.

Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Drug Therapy, Combination; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides; Treatment Failure

This article aims to detail the major innovations occurred in Gastro-enterology in 2016, including the introduction of a new molecule, the vonoprazan, for the treatment of refractory gastroesophagal reflux disease (GERD) and a new way of eradication of H. pylori. The possibility to use an intermittent dose of PPI rather than continuously in severe gastric and duodenal ulcers after successful endoscopic hemostasis is also discussed as well as the withdrawal of corticosteroids in the treatment of autoimmune pancreatitis. The formulation of corticosteroids in the treatment of eosinophilic esophagitis, the interest of the chromo-endoscopy during colonoscopy highlighting small polyps (from 1 to 5 mm = « diminutive polyps ») and the introduction on the Swiss market for biosimilars in the treatment of inflammatory bowel disease (IBD) are also discussed.. Cet article a pour but de détailler les nouveautés majeures survenues en gastroentérologie pour 2016, notamment avec l’introduction d’une nouvelle molécule, le vonoprazan, destiné à la prise en charge du reflux gastro-œsophagien (RGO) réfractaire et des nouvelles modalités d’éradication d’

Topics: Biosimilar Pharmaceuticals; Disease Eradication; Drug Resistance, Bacterial; Duodenal Ulcer; Gastroenterology; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Humans; Pyrroles; Sulfonamides

Vonoprazan (Takecab(®)) is an orally bioavailable potassium-competitive acid blocker (P-CAB) being developed by Takeda for the treatment and prevention of acid-related diseases. The drug is approved in Japan for the treatment of acid-related diseases, including erosive oesophagitis, gastric ulcer, duodenal ulcer, peptic ulcer, gastro-oesophageal reflux, reflux oesophagitis and Helicobacter pylori eradication. Phase III development is underway for the prevention of recurrence of duodenal and gastric ulcer in patients receiving aspirin or NSAID therapy. Phase I development was conducted in the UK for gastro-oesophageal reflux; however, no further development has been reported. This article summarizes the milestones in the development of vonoprazan leading to this first approval for acid-related diseases.

Topics: Animals; Drug Approval; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides

Duodenal ulcers, especially caused by increasingly drug-resistant Helicobacter pylori, are a concern in Asia. We compared oral vonoprazan versus lansoprazole for efficacy (healing duodenal ulcers) and safety in non-Japanese Asian patients.. In this phase 3, randomized (1:1), double-blind, double-dummy, parallel-group, non-inferiority study (April 5, 2017, to July 19, 2019), patients with ≥ 1 endoscopically confirmed duodenal ulcer, at 52 hospitals (China, South Korea, and Taiwan), received vonoprazan 20 mg once daily (QD) or lansoprazole 30 mg QD for 6 weeks maximum. Patients with H. pylori received bismuth-containing quadruple therapy including vonoprazan 20 mg twice daily (BID) or lansoprazole 30 mg BID, for 2 weeks, followed by vonoprazan or lansoprazole monotherapy QD (4 weeks maximum). Endpoints were endoscopically confirmed duodenal ulcer healing (Week 4/6; primary) and H. pylori eradication (4 weeks post-treatment; secondary); non-inferiority margins were -6% and -10%, using a two-sided 95% confidence interval (CI).. Of 533 enrolled patients, one was lost to follow-up and one withdrew (full analysis set: 531 patients [vonoprazan, n = 263; lansoprazole, n = 268]; 85.4% = H. pylori positive). Vonoprazan was non-inferior to lansoprazole for duodenal ulcer healing (96.9% vs 96.5%; difference 0.4% [95% CI -3.00, 3.79]). H. pylori eradication rates were 91.5% (vonoprazan) and 86.8% (lansoprazole; difference 4.7% [95% CI -1.28, 10.69]). Vonoprazan and lansoprazole were well tolerated, with similar safety profiles, no new safety signals; no deaths occurred.. Vonoprazan was well tolerated and non-inferior to lansoprazole for duodenal ulcer healing and achieved H. pylori eradication above the clinically meaningful threshold (90%), in non-Japanese Asian patients.

Topics: Amoxicillin; Anti-Ulcer Agents; Clarithromycin; Double-Blind Method; Drug Therapy, Combination; Duodenal Ulcer; Helicobacter Infections; Helicobacter pylori; Humans; Lansoprazole; Neoplasm Recurrence, Local; Pyrroles; Sulfonamides

Vonoprazan is a new potassium-competitive acid blocker for treatment of acid-related diseases.. To conduct two randomised-controlled trials, to evaluate the non-inferiority of vonoprazan vs. lansoprazole, a proton pump inhibitor, for treatment of gastric ulcer (GU) or duodenal ulcer (DU).. Patients aged ≥20 years with ≥1 endoscopically-confirmed GU or DU (≥5 mm white coating) were randomised 1:1 using double-dummy blinding to receive lansoprazole (30 mg) or vonoprazan (20 mg) for 8 (GU study) or 6 (DU study) weeks. The primary endpoint was the proportion of patients with endoscopically confirmed healed GU or DU.. For GU, 93.5% (216/231) of vonoprazan-treated patients and 93.8% (211/225) of lansoprazole-treated patients achieved healed GU; non-inferiority of vonoprazan to lansoprazole was confirmed [difference = -0.3% (95% CI -4.750, 4.208); P = 0.0011]. For DU, 95.5% (170/178) of vonoprazan-treated patients and 98.3% (177/180) of lansoprazole-treated patients achieved healed DU; non-inferiority to lansoprazole was not confirmed [difference = -2.8% (95% CI -6.400, 0.745); P = 0.0654]. The incidences of treatment-emergent adverse events were slightly lower for GU and slightly higher for DU with vonoprazan than with lansoprazole. There was one death (subarachnoid haemorrhage) in the vonoprazan group (DU). The possibility of a relationship between this unexpected patient death and the study drug could not be ruled out. In both studies, increases in serum gastrin levels were greater in vonoprazan-treated vs. lansoprazole-treated patients; levels returned to baseline after treatment in both groups.. Vonoprazan 20 mg has a similar tolerability profile to lansoprazole 30 mg and is non-inferior with respect to GU healing and has similar efficacy for DU healing.

Topics: Adult; Aged; Anti-Ulcer Agents; Double-Blind Method; Duodenal Ulcer; Endoscopy; Female; Humans; Lansoprazole; Male; Middle Aged; Proton Pump Inhibitors; Pyrroles; Stomach Ulcer; Sulfonamides; Treatment Outcome

The incidence of peptic ulcers unrelated to H. pylori infection and non-steroidal anti-inflammatory drugs (NSAIDs), termed idiopathic peptic ulcers (IPUs), has increased worldwide. We recently reported that IPUs were refractory to proton pump inhibitor (PPI) treatment. Vonoprazan, which was recently developed in Japan, has shown a more potent acid-inhibitory effect than ordinary PPIs. In the present study, we compared the healing rates among peptic ulcers of different etiologies following treatment with vonoprazan.. A multicenter observational study was performed at six participating hospitals in Akita Prefecture, Japan. Consecutive patients who had endoscopically confirmed gastro-duodenal ulcers were enrolled between August 2016 and March 2018. For each patient, the Helicobacter pylori infection status and NSAID use, including aspirin, were checked, and 20 mg vonoprazan was administered for 6 weeks for duodenal ulcers and 8 weeks for gastric ulcers. The healing status was checked by endoscopy at the end of vonoprazan treatment. Patients were divided into four subgroups according to the H. pylori status and NSAID usage.. The proportion of IPUs was 18.2%. A total of 162 patients completed the study protocol. The healing rate of IPUs was marginally lower than that of simple H. pylori-associated ulcers (81.2% vs. 93.5%, P = 0.05). Similarly, the healing rate of NSAID-related ulcers, irrespective of concomitant H. pylori infection, was significantly lower than that of simple H. pylori-associated ulcers.. Six- or 8-week vonoprazan treatment still seems to be insufficient for healing IPUs. Longer-term vonoprazan or another treatment option may be required to heal potentially refractory peptic ulcers.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Cohort Studies; Duodenal Ulcer; Endoscopy, Gastrointestinal; Female; Helicobacter Infections; Helicobacter pylori; Humans; Japan; Male; Middle Aged; Prospective Studies; Proton Pump Inhibitors; Pyrroles; Stomach Ulcer; Sulfonamides; Treatment Outcome