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Safety Profile of Vonoprazan for Long-Term Maintenance Treatment of Erosive Esophagitis
TAKE-HOME MESSAGE
- This phase IV randomized trial studied the 5-year safety profile of vonoprazan compared with that of lansoprazole for the treatment of erosive esophagitis. Patients receiving daily vonoprazan had no malignant alterations of the gastric mucosa or gastric neuroendocrine tumors after 5 years. The safety profile was comparable between vonoprazan and lansoprazole. Median serum gastrin levels were higher in the vonoprazan group than in the lansoprazole group (625 pg/mL vs 200 pg/mL).
- Although daily vonoprazan appears to be safe at 5 years based on these data, careful monitoring is recommended until additional long-term data are obtained.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND & AIMS
Acid secretion inhibitors are associated with hypergastrinemia, which can lead to gastric mucosal changes. Potassium-competitive acid blockers, such as vonoprazan, are more potent than proton pump inhibitors, but long-term safety data are lacking.
METHODS
In this phase IV, randomized trial, patients with erosive esophagitis (EE) received induction therapy (once daily vonoprazan 20 mg or lansoprazole 30 mg; ≤8 weeks). Those with healed EE received maintenance therapy (once daily vonoprazan 10 mg or lansoprazole 15 mg) for 260 weeks (2:1). The primary endpoint was the proportion of patients with malignant epithelial cell alterations, parietal cell hyperplasia, foveolar hyperplasia, enterochromaffin-like (ECL) cell hyperplasia, and G-cell hyperplasia.
RESULTS
Overall, 202/208 patients (vonoprazan, n = 139; lansoprazole, n = 69) achieved healed EE and received maintenance therapy. No malignant alterations or gastric neuroendocrine tumors (NETs) were observed; there was 1 adenoma in each group. At week 260, significantly more patients taking vonoprazan vs lansoprazole had parietal cell hyperplasia (97.1% vs 86.5%) and foveolar hyperplasia (14.7% vs 1.9%); proportions of patients with ECL cell hyperplasia (4.9% vs 7.7%) and G-cell hyperplasia (85.3% vs 76.9%) were similar. Median serum gastrin levels were higher with vonoprazan treatment vs lansoprazole (625 pg/mL vs 200 pg/mL). Incidences of adverse events were comparable for both treatments.
CONCLUSIONS
The exploratory VISION study assessed the safety profile of vonoprazan and lansoprazole over 5 years in Japanese patients with healed EE. Although gastrin concentration, parietal cell hyperplasia, and foveolar hyperplasia were higher in the vonoprazan group, there was no increased risk of malignant epithelial cell alterations and gastric NETs. (ClinicalTrials.gov, NCT02679508).
Additional Info
Disclosure statements are available on the authors' profiles:
Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study
Clin. Gastroenterol. Hepatol. 2024 Aug 27;[EPub Ahead of Print], N Uemura, Y Kinoshita, K Haruma, R Kushima, T Yao, J Akiyama, N Aoyama, Y Baba, C Suzuki, K IshiguroFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Vonoprazan, the first-in-class of acid-reducing agents, potassium-competitive acid blockers (PCABs), is approved in the US. The mechanism of action offers several potential advantages over the currently available delayed-release proton pump inhibitors (PPIs). It has a more rapid onset (steady state in 1–2 days compared with 5–7 days for once-daily PPI), has similar intragastric pH control regardless of relationship to food or time of day, which unlike PPIs allows for dosing flexibility, and is efficacious independent of CYP2C19 polymorphism. In Western populations, the median time intragastric pH>4 for 10 and 20 mg once-daily dosing is 60.2% and 85.2%, respectively, of a 24-hour period. A dose of 10 mg (approved dose for maintenance and non-erosive disease) is likely equivalent to 60 mg omeprazole daily, and a 20 mg dose (the approved dose for healing erosive esophagitis) is likely equivalent to esomeprazole 40 mg BID.1 These differences offer the potential to augment our treatment options for patients with gastroesophageal reflux disease (GERD), especially those who might benefit from enhanced acid control. In the acute setting, I prescribe it first line for patients with LA grade C or D esophagitis and offer it to any patients with objective evidence of GERD who require BID PPI for healing or symptom control. Current cost and availability issues may affect my current use. I find that many patients have difficulty with BID PPI, particularly optimizing the evening dose owing to variability in daily schedules, travel, and shift work. PCABs can be a welcome option in these patients, overall reducing the need for BID PPI. In the acute setting, adverse events are minimal, comparable with once-daily PPIs; thus, there is little reason, other than cost, not to use PCABs where a clear advantage or benefit to the patient might be present.
Despite widespread, worldwide use for over 35 years, there continues concern and debate regarding the frequency of potential adverse events in patients on long-term PPIs. It is not surprising that the long-term effects of even greater acid suppression by PCABs will remain a concern. To date, 10 years of experience in Japan has shown no major signal of any major adverse event. Reports of increased GI infections, renal or bone, cardiac, or neurologic issues, or B12 absorption have not surfaced. The study highlighted below, a 5-year randomized study comparing vonoprazan 10 mg daily to lansoprazole 15 mg daily, confirmed PCAB efficacy, and found more parietal cell and foveolar hyperplasia but similar enterochromaffin-like cell and G-cell hyperplasia comparing PCAB and PPI at the maintenance dose. Gastrin levels were higher, as might be expected with the greater acid control with the PCAB. No malignancies developed in this small group in this time frame. These data are comforting; however, it is likely that safety concerns will remain, as they should for any medication used long term.
The initial good news continues, as efficacy and safety data evolve and other PCABs come to market. It is important to remember that most patients with GERD will have non-erosive reflux disease and should be easily managed with effective lifestyle modification and low-dose PPI. Therefore, PCABs should not be needed in most. However, patients with LA C and D erosions, and many with grade B will need long-term maintenance, many with “full dose” once-daily PPI. Whether PCABs will be needed in these patients remains to be seen. For the true few patients with “proven” GERD incompletely relieved with once-daily PPI, regurgitation predominant or atypical symptoms, or overall rare special clinical circumstances (Barrett’s esophagus, not achieving remission with ablation, refractory peptic strictures), PCABs may offer sufficient advantage. As with all new drugs, we should use the class with an open mind as data evolve. We cannot deny that PCABs are a valuable addition to our GERD treatment armamentarium, better for some today. As efficacy and safety data evolve, their place will evolve with it.
Reference
1. Graham DY, Tansel A. Interchangeable Use of Proton Pump Inhibitors Based on Relative Potency. Clin Gastroenterol Hepatol. 2018;16(6):800-808.e7. https://www.cghjournal.org/article/S1542-3565(17)31168-0/fulltext