Steven Flamm, K. Rajender Reddy, Neddie Zadeikis, Tarek Hassanein, Bruce R. Bacon, Andreas Maieron, Stefan Zeuzem, Marc Bourliere, Jose L. Calleja, Matthew P. Kosloski, Rajneet K. Oberoi, Chih-Wei Lin, Yao Yu, Sandra Lovell, Dimitri Semizarov, Federico J. Mensa
- BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are commonly prescribed to treat acid-related disorders. Some direct-acting antiviral regimens for chronic hepatitis C virus (HCV) infection have reduced efficacy in patients taking concomitant acid-reducing agents, including PPIs, due to interactions between drugs. We analyzed data from 9 multicenter, phase 2 and 3 trials to determine the efficacy and pharmacokinetics of an HCV therapeutic regimen comprising glecaprevir and pibrentasvir (glecaprevir/pibrentasvir) in patients taking concomitant acid-reducing agents.
METHODS: We analyzed data from 2369 patients infected with HCV genotypes 1-6 and compensated liver disease treated with an all-oral regimen of glecaprevir/pibrentasvir for 8-16 weeks. We compared efficacy and pharmacokinetics among patients receiving at least 1 dose of an acid-reducing agent (a PPI, an H2 blocker, or antacid). High-dose PPI was defined as daily dose greater than 20 mg omeprazole dose equivalent. The objectives were to evaluate rate of sustained virologic response 12 weeks post-treatment (SVR12) and to assess steady-state glecaprevir and pibrentasvir exposures in patients on acid-reducing agents.
RESULTS: Of the 401 patients (17%) who reported use of acid-reducing agents, 263 took PPIs (11%; 109 patients took a high-dose PPI and 154 patients took a low-dose PPI). Rates of SVR12 were 97.0% among patients who used acid-reducing agents and 97.5% among those not using acid-reducing agents (P = .6). An SVR12 was achieved in 96.3% taking a high-dose PPI and 97.4% taking a low-dose PPI, with no virologic failures in those receiving a high-dose PPI (P = .7). Glecaprevir, but not pibrentasvir, bioavailability was affected; its exposure decreased by 41% in patients taking a high-dose PPI.
CONCLUSIONS: In an analysis of data from 9 clinical trials, we observed a high rate of SVR12 (approximately 97%) among patients treated with glecaprevir/pibrentasvir for HCV infection-even among patients taking concomitant ARA or high-dose PPI. This was despite decreased glecaprevir exposures in patients when on high-dose PPIs. ClinicalTrials.gov numbers, NCT02243280 (SURVEYOR-I), NCT02243293 (SURVEYOR-II), NCT02604017 (ENDURANCE-1), NCT02640482 (ENDURANCE-2), NCT02640157 (ENDURANCE-3), NCT02636595 (ENDURANCE-4), NCT02642432 (EXPEDITION-1), NCT02651194 (EXPEDITION-4), NCT02446717 (MAGELLAN-I).
MetadatenAuthor: | Steven Flamm, K. Rajender ReddyORCiDGND, Neddie Zadeikis, Tarek Hassanein, Bruce R. Bacon, Andreas MaieronORCiDGND, Stefan ZeuzemORCiDGND, Marc Bourliere, Jose L. Calleja, Matthew P. Kosloski, Rajneet K. Oberoi, Chih-Wei Lin, Yao Yu, Sandra Lovell, Dimitri Semizarov, Federico J. Mensa |
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URN: | urn:nbn:de:hebis:30:3-544829 |
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DOI: | https://doi.org/10.1016/j.cgh.2018.07.003 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/30012435 |
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Parent Title (English): | Clinical gastroenterology and hepatology |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2018/09/10 |
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Date of first Publication: | 2018/09/10 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2020/04/09 |
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Tag: | ARA; DAA; combination; drug interaction |
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Volume: | 17 |
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Issue: | 3 |
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Page Number: | 15 |
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First Page: | 527 |
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Last Page: | 535 |
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Note: | This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
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HeBIS-PPN: | 464656575 |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |
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