grazoprevir and Kidney-Failure--Chronic

In some parts of the world, hepatitis C virus (HCV) infection remains a huge problem for kidney transplant candidates and kidney transplant (KT) recipients. Until 2 years ago, anti-HCV treatment for the general population relied on pegylated alpha-interferon plus ribavirin, but led to a sustained viral response (SVR) in <50% of cases. This treatment was contraindicated in KT patients because of acute-rejection issues and was poorly tolerated in patients with end-stage renal disease (ESRD). Over the last year, direct-acting antiviral agents (DAAs) have entered the market and are associated in the general population with a SVR of >90%, whatever the patient's HCV genotype. In KT patients, sofosbuvir-based therapy is associated with a SVR at nearly 100% in patients with a HCV genotype-1 infection, with almost no side effects and only mild interference with immunosuppressive drugs. Most HCV(+) patients with ESRD are genotype 1: in that setting, a recent study reported that the association of grazoprevir/elbasvir 100/50 mg/day led to a SVR of nearly 95% with very few side effects. Thus, it is concluded that DAAs can be safely used and lead to results in KT candidates and KT patients that are as good as those observed in the nonrenal population.

Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Immunosuppressive Agents; Interferon-alpha; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Polyethylene Glycols; Quinoxalines; Ribavirin; Sulfonamides; Transplant Recipients

To describe the phase 1 and population pharmacokinetic investigations that support dosing recommendations for elbasvir/grazoprevir (EBR/GZR) in hepatitis C virus-infected people with advanced chronic kidney disease.. This was an open-label, two-part, multiple-dose trial (MK-5172 PN050; NCT01937975) in 24 non-HCV-infected participants with end-stage renal disease (ESRD) or severe renal impairment who received once-daily EBR 50 mg and GZR 100 mg for 10 days. Population pharmacokinetic analyses from the phase 3 C-SURFER study (PN052, NCT02092350) were also conducted.. When comparing haemodialysis (HD) and non-HD days in participants with ESRD, geometric mean ratios (GMRs) (90% confidence intervals [CIs]) for EBR and GZR AUC. EBR/GZR represents an important treatment option for HCV infection in people with severe renal impairment and those with ESRD. No dosage adjustment of EBR/GZR is required in people with any degree of renal impairment, including those receiving dialysis.

Topics: Adult; Amides; Antiviral Agents; Benzofurans; Carbamates; Cyclopropanes; Drug Therapy, Combination; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Kidney Failure, Chronic; Male; Middle Aged; Quinoxalines; Renal Dialysis; Sulfonamides

To assess the cost-effectiveness of the elbasvir/grazoprevir (EBR/GZR) regimen in patients with genotype 1 chronic hepatitis C virus (HCV) infection with severe and end-stage renal disease compared to no treatment.. This study uses a health economic model to estimate the cost-effectiveness of treating previously untreated and treatment experienced chronic hepatitis C patients who have severe and end stage renal disease with the elbasvir-grazoprevir regimen versus no treatment in the French context. The lifetime homogeneous markovian model comprises of forty combined health states including hepatitis C virus and chronic kidney disease. The model parameters were from a multicentre randomized controlled trial, ANRS CO22 HEPATHER French cohort and literature. 1000 Monte Carlo simulations of patient health states for each treatment strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The results were expressed in cost per quality-adjusted life year (QALY) gained.. The mean age of patients in the HEPATHER French cohort was 59.6 years and 56% of them were men. 22.3% of patients had a F0 fibrosis stage (no fibrosis), 24.1% a F1 stage (portal fibrosis without septa), 7.1% a F2 stage (portal fibrosis with few septa), 21.4% a F3 stage (numerous septa without fibrosis) and 25% a F4 fibrosis stage (compensated cirrhosis). Among these HCV genotype 1 patients, 30% had severe renal impairment stage 4, 33% had a severe renal insufficiency stage 5 and 37% had terminal severe renal impairment stage 5 treated by dialysis.. Fixed-dose combination of direct-acting antiviral agents elbasvir and grazoprevir compared to no-treatment.. EBR/GZR increased the number of life years (6.3 years) compared to no treatment (5.1 years) on a lifetime horizon. The total number of QALYs was higher for the new treatment because of better utility on health conditions (6.2 versus 3.7 QALYs). The incremental cost-utility ratio (ICUR) was of €15,212 per QALY gained for the base case analysis.. This cost-utility model is an innovative approach that simultaneously looks at the disease evolution of chronic hepatitis C and chronic kidney disease. EBR/GZR without interferon and ribavirin, produced the greatest benefit in terms of life expectancy and quality-adjusted life years (QALY) in treatment-naïve or experienced patients with chronic hepatitis C genotype 1 and stage 4-5 chronic kidney disease including dialysis patients. Based on shape of the acceptability curve, EBR/GZR can be considered cost-effective at a willingness to pay of €20,000 /QALY for patients with renal insufficiency with severe and end-stage renal disease compared to no treatment.

Topics: Amides; Antiviral Agents; Benzofurans; Carbamates; Cost-Benefit Analysis; Cyclopropanes; Drug Therapy, Combination; Female; France; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Imidazoles; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Models, Economic; Quality-Adjusted Life Years; Quinoxalines; Randomized Controlled Trials as Topic; Renal Dialysis; RNA, Viral; Sulfonamides