Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates
Abstract Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H2–receptor antagonists (H2RAs). Emerging evidence also supports potassium‐competitive acid blockers (P‐CABs). The aim was to c...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.13235 |
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| author | Colin W. Howden Carmelo Scarpignato Eckhard Leifke Darcy J. Mulford Gezim Lahu Axel Facius Yuhong Yuan Richard Hunt |
| author_facet | Colin W. Howden Carmelo Scarpignato Eckhard Leifke Darcy J. Mulford Gezim Lahu Axel Facius Yuhong Yuan Richard Hunt |
| author_sort | Colin W. Howden |
| collection | DOAJ |
| description | Abstract Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H2–receptor antagonists (H2RAs). 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 H2RAs, PPIs and P‐CABs. By literature search, we identified studies of H2RAs, 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 H2RAs. P‐CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis. |
| format | Article |
| id | doaj-art-6d6d4604ed3443ea9cc060e75bd8948e |
| institution | Kabale University |
| issn | 2163-8306 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | CPT: Pharmacometrics & Systems Pharmacology |
| spelling | doaj-art-6d6d4604ed3443ea9cc060e75bd8948e2025-01-07T20:48:59ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062025-01-01141284110.1002/psp4.13235Mathematical model of the relationship between pH holding time and erosive esophagitis healing ratesColin W. Howden0Carmelo Scarpignato1Eckhard Leifke2Darcy J. Mulford3Gezim Lahu4Axel Facius5Yuhong Yuan6Richard Hunt7University of Tennessee College of Medicine Memphis Tennessee USADepartment of Health Sciences United Campus of Malta Msida MaltaPhathom Pharmaceuticals Research and Development Buffalo Grove Illinois USAPhathom Pharmaceuticals Research and Development Buffalo Grove Illinois USAthinkQ2 AG Baar SwitzerlandthinkQ2 AG Baar SwitzerlandDivision of Gastroenterology, Department of Medicine McMaster University Hamilton Ontario CanadaDivision of Gastroenterology, Department of Medicine McMaster University Hamilton Ontario CanadaAbstract Effective suppression of gastric acid secretion promotes healing of erosive esophagitis. Treatment guidelines recommend proton pump inhibitors (PPIs) and histamine H2–receptor antagonists (H2RAs). 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 H2RAs, PPIs and P‐CABs. By literature search, we identified studies of H2RAs, 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 H2RAs. P‐CABs provide the longest duration with intragastric pH >4 and, accordingly, the highest healing rates of erosive esophagitis.https://doi.org/10.1002/psp4.13235 |
| spellingShingle | Colin W. Howden Carmelo Scarpignato Eckhard Leifke Darcy J. Mulford Gezim Lahu Axel Facius Yuhong Yuan Richard Hunt Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates CPT: Pharmacometrics & Systems Pharmacology |
| title | Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates |
| title_full | Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates |
| title_fullStr | Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates |
| title_full_unstemmed | Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates |
| title_short | Mathematical model of the relationship between pH holding time and erosive esophagitis healing rates |
| title_sort | mathematical model of the relationship between ph holding time and erosive esophagitis healing rates |
| url | https://doi.org/10.1002/psp4.13235 |
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