Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates.

Autor: Howden CW; University of Tennessee College of Medicine, Memphis, Tennessee, USA., Scarpignato C; Department of Health Sciences, United Campus of Malta, Msida, Malta., Leifke E; Phathom Pharmaceuticals, Research and Development, Buffalo Grove, Illinois, USA., Mulford DJ; Phathom Pharmaceuticals, Research and Development, Buffalo Grove, Illinois, USA., Lahu G; thinkQ2 AG, Baar, Switzerland., Facius A; thinkQ2 AG, Baar, Switzerland., Yuan Y; Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.; Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada., Hunt R; Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.; Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2024 Sep 19. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1002/psp4.13235
Abstrakt: Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H 2 -receptor antagonists (H 2 RAs). Emerging evidence also supports potassium-competitive acid blockers (P-CABs). The aim was to construct a mathematical model to examine the relationship between pH holding time ratios (HTRs) and erosive esophagitis healing rates with H 2 RAs, PPIs and P-CABs. By literature search, we identified studies of H 2 RAs, PPIs or P-CABs that reported mean pH >4 HTRs at steady state (days 5-8) and erosive esophagitis healing rates after 4 and/or 8 weeks. We aggregated treatments by drug class and developed a non-linear, mixed-effects model to explore the relationship between pH >4 HTRs and healing rates. The pH dataset included 82 studies (4297 participants; 201 dosage arms); healing rate data came from 103 studies (43,417 patients; 196 treatment arms). P-CABs achieved the longest periods with intragastric pH >4, and the highest healing rates after 4 and 8 weeks. The predicted probabilities of achieving ≥90% healing rates at 8 weeks were 74.1% for P-CABs, 17.3% for PPIs and 0% for H 2 RAs. P-CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis.
(© 2024 The Author(s). CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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