Real-world safety and effectiveness of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in hepatitis C virus genotype 1- and 4-infected patients with diverse comorbidities and comedications: A pooled analysis of post-marketing observational studies from 13 countries

Peter Ferenci, Stefan Bourgeois, Peter Buggisch, Suzanne Norris, Manuela Curescu, Dominique Larrey, Fiona Marra, Henning Kleine, Patrick Dorr, Mariem Charafeddine, Eric Crown, Mark Bondin, David Back, Robert Flisiak, Peter Ferenci, Stefan Bourgeois, Peter Buggisch, Suzanne Norris, Manuela Curescu, Dominique Larrey, Fiona Marra, Henning Kleine, Patrick Dorr, Mariem Charafeddine, Eric Crown, Mark Bondin, David Back, Robert Flisiak

Abstract

Ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) regimens show high efficacy and good tolerability in clinical trials for chronic hepatitis C virus (HCV) genotypes (GT) 1 or 4. To evaluate whether these results translate to clinical practice, data were pooled from observational studies across 13 countries. Treatment-naïve or -experienced patients, with or without cirrhosis, received OBV/PTV/r ± DSV ± RBV according to approved local labels and clinical practice. Sustained virologic response at post-treatment Week 12 (SVR12), adverse events (AEs) and comedication management were assessed for patients initiating treatment before 1 June 2017. The safety population included 3850 patients who received ≥1 dose of study drug. The core population (N = 3808) further excluded patients with unknown GT or cirrhosis status, or who received off-label treatment. Patients had HCV GT1a (n = 732; 19%), GT1b (n = 2619; 69%) or GT4 (n = 457; 12%). In 3546 patients with sufficient follow-up data at post-treatment Week 12, the SVR12 rate was 96% (n/N = 3401/3546 [95% CI 95.2-96.5]). In patients with or without cirrhosis, SVR12 was comparable (96%). In patients with HCV GT1a, GT1b or GT4, SVR12 rates were 93%, 97% and 94%. In GT1b-infected patients with planned treatment for 8 weeks, SVR12 was 96%. In patients with ≥1 comorbidity (67%), SVR12 was 95%. 58% of patients received ≥1 comedication, and there was minimal impact on SVR12 rates using comedications for peptic ulcers and gastro-esophageal reflux disease, statins, antipsychotics or antiepileptics. Most comedications were maintained during treatment although 58% of patients changed their statin medication. AEs and serious AEs occurred in 26% and 3% of patients. Post-baseline Grade 3-4 laboratory abnormalities were rare (<3%), and discontinuation rates were low (<4%). Real-world evidence confirms the effectiveness of OBV/PTV/r ± DSV ± RBV in patients with HCV GT1 or GT4, regardless of common comorbidities or comedications, and is consistent with clinical trial results. Adverse safety outcomes may be limited by underreporting in the real-world setting.

Trial registration: ClinicalTrials.gov NCT02582658 NCT02581163 NCT02581189 NCT02851069 NCT02618928 NCT02615145 NCT02725866 NCT02636608 NCT02582671 NCT02803138 NCT02798315 NCT02640547 NCT02807402.

Keywords: comorbidity; direct-acting antiviral; drug-drug interaction; hepatitis C virus; real-world evidence.

Conflict of interest statement

P Ferenci: Lectures and/or travel support: AbbVie and Gilead; Unrestricted research grant: Gilead; Global advisor: Merck; Lectures: BMS; Advisor: Gilead (Austria), BMS (Austria), AbbVie (Austria), Janssen (Austria). S Bourgeois: Advisory board and speakers fees: AbbVie, Gilead, Janssen, BMS, MSD. P Buggisch: Speakers bureau/advisory board: AbbVie, BMS, Falk, Gilead, Janssen, Merz Pharma, MSD. S Norris: Participated in AbbVie‐sponsored clinical studies. M Curescu: Advisory board, principal investigator and/or speaker: BMS, MSD, Roche, AbbVie, Janssen. D Larrey: AbbVie, Gilead, Janssen, BMS, MSD. F Marra: Educational grants or consultancies: Merck, Gilead, AbbVie, ViiV, Janssen. D Back: Research or educational grants received: AbbVie, Gilead, MSD, Janssen; Honoraria for lectures or advisory boards: AbbVie, Gilead, MSD, Janssen. R Flisiak: Served as advisor: AbbVie, Gilead, BMS, Merck, Novartis, Janssen, Roche; Speaker honoraria during the last year from: AbbVie, Gilead, BMS. H Kleine, P Dorr, M Charafeddine, E Crown, and M Bondin: Employees of AbbVie and may hold stock or options.

© 2019 The Authors. Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
SVR12 rates by HCV genotype/subtype and cirrhosis status in (A) the overall population, (B) patients with prior treatment experience, (C) by ribavirin treatment (CPSFU population) and (D) by baseline comorbidity subgroups. Error bars represent 95% confidence intervals. †Patients infected with GT1a include those with other/unknown subtypes except G1b. CPSFU, core population with sufficient follow‐up; GT, genotype; HCV, hepatitis C virus; RBV, ribavirin; SVR12, sustained virologic response at post‐treatment Week 12

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