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

Disclosures

J Viral Hepat. 2019;26(6):685-696. 

In This Article

Abstract and Introduction

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.

Introduction

Since their introduction in 2013, second-generation direct-acting antiviral (DAA) drugs have improved the efficacy, safety and tolerability of treatment for chronic hepatitis C virus (HCV) infection. All-oral, interferon-free DAA combination regimens comprising ombitasvir/paritaprevir/ritonavir + dasabuvir (OBV/PTV/r+DSV) ± ribavirin (RBV) and OBV/PTV/r + RBV were approved for use in the United States and Europe in 2014–2015[1–4] and are recommended for the treatment of HCV genotypes (GT) 1 and 4, respectively.[5,6] In GT1a-infected patients without cirrhosis, OBV/PTV/r + DSV + RBV is administered for 12 weeks, or for 24 weeks in patients with compensated cirrhosis. In GT1b-infected patients without cirrhosis or with compensated cirrhosis, OBV/PTV/r + DSV is administered for 12 weeks (or 8 weeks with mild fibrosis [F0-F2]).[2,3] In GT4-infected patients, OBV/PTV/r + RBV is administered for 12 weeks regardless of cirrhosis status.[1–4] These multitargeted DAA regimens have shown good tolerability and high rates of sustained virologic response at post-treatment Week 12 (SVR12) in a broad range of adult patients in pivotal clinical trials.[7–12] As of April 2017, OBV/PTV/r + DSV regimens are approved in more than 80 countries, and OBV/PTV/r in more than 50 countries.

Notwithstanding the success of DAA regimens, barriers to HCV treatment initiation remain, with the presence of comorbidities and the potential risk for drug-drug interactions (DDIs) cited as common impediments.[5] Patients with chronic HCV infection have a high burden of comorbid medical and psychiatric conditions,[13–15] which are often managed with multiple comedications.[16] Among patients treated with currently available DAA drugs who are taking comedications, at least 30% are potentially at risk for clinically significant DDIs,[17] although these risks vary between individual drugs. Clinically significant DDIs with commonly prescribed drugs and over-the-counter medications have been established for OBV/PTV/r ± DSV based on drug interaction studies.

In clinical practice, the effectiveness of DAA therapies may be lower than in clinical trials because patient populations tend to be more diverse (eg patients may be older, have more advanced disease or have additional comorbidities) and less adherent to treatment regimens.[18] Furthermore, clinical trials are designed to establish efficacy outcomes of investigative drugs and are conducted in controlled settings, with strict eligibility criteria that are intended to enroll well-defined trial populations with limited comorbidities or comedications to mitigate any unwarranted influence on treatment safety and efficacy outcomes. Therefore, the results from clinical trials may not be comparable to those from daily clinical practice. Studies using real-world data collected during routine clinical care provide additional evidence of treatment safety and effectiveness, which complements the results from clinical trials. Understanding the safety and effectiveness of DAA regimens in real-world settings is important to help guide patients and healthcare providers in clinical decision-making as well as to help inform regulatory decision-making.[19] At present, data assessing the real-world effectiveness of OBV/PTV/r ± DSV ± RBV regimens in patients with HCV are limited.

In this pooled analysis of post-marketing observational studies, we evaluated the real-world safety and effectiveness of OBV/PTV/r ± DSV ± RBV regimens, as well as comedication management, in clinical practice in patients chronically infected with HCV GT1 or GT4.

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