Clinical management of drug-drug interactions in HCV therapy: Challenges and solutions.

Contains fulltext : 118153.pdf (Publisher’s version ) (Open Access) Hepatitis C virus (HCV) infected patients often take multiple co-medications to treat adverse events related to HCV therapy, or to manage other co-morbidities. Drug-drug interactions associated with this polypharmacy are relatively new to the field of HCV pharmacotherapy. With the advent of the direct-acting antivirals telaprevir and boceprevir, which are both substrates and inhibitors of the cytochrome P450 (CYP) 3A iso-enzyme, knowledge and awareness of drug-drug interactions have become a cornerstone in the evaluation of patients starting and continuing HCV combination therapy. In our opinion, an overview of conducted dr…

Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial

Although the addition of the HCV NS3/4A protease inhibitors boceprevir and telaprevir to pegylated interferon (peginterferon) alfa plus ribavirin has improved sustained virological response (SVR) in treatment-naive and treatment-experienced patients infected with hepatitis C virus (HCV) genotype 1, the regimens have a high pill burden and are associated with increased rates and severity of adverse events, such as anaemia and rash. The efficacy and safety of the combination of simeprevir, a one pill, once-daily, oral HCV NS3/4A protease inhibitor, plus peginterferon alfa 2a plus ribavirin were assessed in treatment-naive patients with HCV genotype 1 infection.In QUEST-1, a phase 3, randomise…

Efficacy and Safety of Elbasvir/Grazoprevir in Patients with Chronic Hepatitis C Virus Infection and Inherited Blood Disorders: Final Data from the C-Edge Ibld Study

Abstract Background: Complications from chronic hepatitis C virus (HCV) infection are a major cause of morbidity and mortality among individuals with inherited blood disorders (IBLD). Inability to tolerate ribavirin and frequent comorbidities have limited HCV treatment options in these patients. The aim of the C-EDGE IBLD study was to evaluate the efficacy and safety of a once-daily, fixed-dose combination of elbasvir 50 mg (EBR, an NS5A inhibitor) and grazoprevir 100 mg (GZR, an NS3/4A protease inhibitor) in patients with HCV infection and IBLD, including those with hemoglobinopathies. Methods: C-EDGE-IBLD was a randomized, double-blind, placebo-controlled study of treatment-naïve and trea…

Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel.

AbstractChelation therapy with new drugs prevents cardiac damage and improves the survival of thalassemia patients. Liver diseases have emerged as a critical clinical issue. Chronic liver diseases play an important role in the prognosis of thalassemia patients because of the high frequency of viral infections and important role of the liver in regulating iron metabolism. Accurate assessment of liver iron overload is required to tailor iron chelation therapy. The diagnosis of hepatitis B virus– or hepatitis C virus–related chronic hepatitis is required to detect patients who have a high risk of developing liver complications and who may benefit by antiviral therapy. Moreover, clinical manage…

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed …

Efficacy of a 12-Week Simeprevir Plus Peginterferon/Ribavirin (PR) Regimen in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection and Mild-To-Moderate Fibrosis Displaying Early On-Treatment Virologic Response

Background HCV GT4 accounts for up to 20% of HCV infections worldwide. Simeprevir, given for 12 weeks as part of a 24- or 48-week combination regimen with PR is approved for the treatment of chronic HCV GT4 infection. Primary study objectives were assessment of efficacy and safety of simeprevir plus PR in treatment-naïve patients with HCV GT4 treated for 12 weeks. Primary efficacy outcome was sustained virologic response 12 weeks post-treatment (SVR12). Additional objectives included investigation of potential associations of rapid virologic response and baseline factors with SVR12. Methods This multicentre, open-label, single-arm study (NCT01846832) evaluated efficacy and safety of simepre…

Combination therapy with amantadine and interferon in naı̈ve patients with chronic hepatitis C: meta-analysis of individual patient data from six clinical trials

Abstract Background/Aims In chronic hepatitis C, clinical trials evaluating the efficacy of amantadine (AMA) and interferon (INF) compared to INF monotherapy, have produced conflicting results. We performed a meta-analysis of the individual patient's data from previous studies. Methods Nine hundred and seventy-two patients from six European centres were evaluated by means of individual patient meta-analysis, using mixed models with centres and the centre–treatment interaction fitted as random variables. Results At the end of therapy, virological responses were 38.5% (95% CI 34.1–42.8) after INF and AMA, and 29.5% (95% CI 25.5–33.6) after INF alone (P=0.003). Sustained response occurred in 1…

An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1)

Background: Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12) and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12. Methods: In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0-F2 fibrosis, patients with HCV-RNA 12-week regimen. Conclusions: Overall SVR12 rate (66%) was below the target of 80%, indicating that sho…

X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis

Background & aims: Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. Methods: We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Results: Single-marker association analyses found approximately 100 loci displaying P < 5 × 10-4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10-6; odds…

P0792 : Baseline factors associated with increased SVR rates in 123 treatment-naïve chronic HCV genotype 1 patients treated with a shortened 12-week simeprevir plus pegylated interferon and ribavirin regimen: a multivariate analysis

PTH-137 Safety and efficacy of simeprevir (SMV) plus PEG-IFN/RBV in treatment-naÏve chronic hepatitis c genotype 1 patients eligible for 12 weeks of treatment

Introduction HPC3014 is a Phase 3, open-label study to assess if response to SMV+Peg-IFN/RBV at Week 2 can allow shortening of treatment to 12 weeks, irrespective of baseline and on-treatment factors. Method Treatment-naive chronic HCV G1-infected patients with no-to-moderate fibrosis (METAVIR F0–F2) were recruited. In patients with HCV-RNA ® Taqman ® lower limit of quantification: 25 IU/mL, lower limit of detection: 15 IU/mL]) at Week 2 and undetectable at Weeks 4 and 8, all treatments were stopped at Week 12 (12-week group). If these criteria were not met, Peg-IFN/RBV was continued to Week 24 (in one case extended to Week 48). Results 123/163 (76%) patients treated were eligible for the 1…

The case for simplifying and using absolute targets for viral hepatitis elimination goals

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes …