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. 2016 Jun;111(6):845-51.
doi: 10.1038/ajg.2016.108. Epub 2016 Apr 5.

Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With or Without Ribavirin in HCV-Infected Patients Taking Concomitant Acid-Reducing Agents

Mitchell L Shiffman  1 , Vinod Rustgi  2 , Michael Bennett  3 , Xavier Forns  4 , Tarik Asselah  5 , Ramon Planas Vila  6 , Li Liu  7 , Marcos Pedrosa  7 , Jonathan Moller  7 , Nancy Reau  8
Affiliations

Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With or Without Ribavirin in HCV-Infected Patients Taking Concomitant Acid-Reducing Agents

Mitchell L Shiffman et al. Am J Gastroenterol. 2016 Jun.

Erratum in

Abstract

Objectives: Acid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that increase gastric pH can alter the bioavailability of antiviral drugs, particularly relevant in patients with advanced liver disease caused by chronic hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six phase 3 studies, we report the safety and efficacy of the 3-direct-acting antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir-boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV, an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1 patients taking concomitant ARAs and PPIs.

Methods: Treatment-naïve or peginterferon/RBV treatment-experienced patients with or without compensated cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of sustained virologic response (SVR), defined as HCV RNA below the lower limit of quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in patients who were receiving concomitant ARAs.

Results: Among 2,053 patients enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95% confidence interval (CI) 93.5-97.4%) among patients receiving an ARA, and 96.3% (95% CI 95.3-97.2%) in patients not receiving a concomitant ARA. Similarly, among patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1-97.0%) and 96.4% (95% CI 95.5-97.2%), respectively. Response rates were high regardless of treatment regimen (with or without RBV), and among patients receiving a standard or high dose of PPIs. Regarding safety, adverse events and serious adverse events were more frequently reported in patients taking concomitant ARAs, though baseline population differences may have played a role.

Conclusions: In phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients, SVR12 rates were high regardless of ARA/PPI use or PPI dose. These data support the co-administration of this regimen with ARAs including PPIs.

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Conflict of interest statement

Guarantor of the article: Mitchell L. Shiffman, MD.

Specific author contributions: Study investigators and took part in conducting the studies, collecting and interpreting the data: Mitchell L. Shiffman, Vinod Rustgi, Michael Bennett, Xavier Forns, Tarik Asselah, Ramon Planas Vila, and Nancy Reau. All authors provided critical revision during the drafting of the manuscript. All authors approved the final version of the manuscript submitted.

Financial support: AbbVie sponsored the studies, contributed to their designs, participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the manuscript.

Potential competing interests: Mitchell L. Shiffman: Advisor: AbbVie, Achillion, Bristol-Myers Squibb, Gilead, Merck; grant/research support: AbbVie, Achillion, Beckman-Colter, Bristol-Myers Squibb, Gilead, Intercept, Lumena, Novartis; Speaker: AbbVie, Bayer, Gilead, Janssen, Merck. Vinod Rustgi: Research support: AbbVie, Gilead, Hyperion, Inovio; Advisory Board: AbbVie, Bristol-Myers Squibb, Gilead, Merck. Michael Bennett: Stock: AbbVie. Xavier Forns: Grant support: Jansen; Advisor: Janssen, Gilead, AbbVie. Tarik Asselah: Clinical investigator, speaker, and/or consultant for AbbVie, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceuticals, Merck Sharp & Dohme, and Roche. Ramon Planas Vila: Research support from Roche, MSD, BMS, Gilead, Janssen; advisory board/speaker for AbbVie, Roche, MSD, BMS, Gilead, Janssen; speaker for Roche, MSD, BMS, Gilead, Janssen. Li Liu, Marcos Pedrosa, Jonathan Moller: AbbVie employees and may hold AbbVie stock or options. Nancy Reau: Research support: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Merck; Consultant: AbbVie, Bristol-Myers Squibb, Gilead, Merck.

Figures

Figure 1
Figure 1
SVR12 rates in patients receiving OBV/PTV/r+DSV with or without RBV by concomitant use of ARAs or PPIs. SVR12 rates are shown by treatment regimen and concomitant use of ARAs or PPIs (a), and with standard, high, or undetermined PPI doses (b). The standard PPI dose for omeprazole, esomeprazole, and rabeprazole was ≤20 mg, ≤30 mg for dexlansoprazole, ≤15 mg for lansoprazole, and ≤40 mg for pantoprazole. Above these cutoffs was considered as a high PPI dose. ARA, acid-reducing agent; DSV, dasabuvir; OBV, ombitasvir; PPI, proton-pump inhibitor; PTV, paritaprevir; r, ritonavir; RBV, ribavirin; SVR, sustained virologic response.
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