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Background: Hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in patients with chronic kidney disease (CKD). The objective of this study was to predict the impact of EBR/GZR on the incidence of liver and kidney related complications compared with no treatment (NoTx) and pegylated interferon plus ribavirin (pegIFN/RBV) in patients with CKD stage 4/5 in Vietnam. Methods: We developed a mathematical model of the natural history of chronic HCV, CKD, and liver disease. Efficacy of EBR/GZR and pegIFN/RBV were derived from the C-SURFER trial and a meta-analysis, respectively. We calculated lifetime cumulative morbidity and mortality rates, including incidence of decompensated cirrhosis (DC), hepatocellular carcinoma (HCC), and life expectancy. Results: Estimated lifetime incidence of DC was significantly reduced in patients receiving EBR/GZR (3.47%) compared to NoTx (18.14%) and pegIFN/RBV (9.01%). Estimated incidence of HCC was 1.02%, 21.64%, and 8.90%, and 1.02% in patients receiving EBR/GZR, NoTx, and pegIFN/RBV. EBR/GZR was estimated to extend life expectancy by 4.2 and 2.0 years compared with NoTx and pegIFN/RBV. Conclusions: Our model predicted that EBR/GZR will significantly reduce the incidence of liver-related complications and prolong life in patients with chronic HCV GT1 infection and CKD compared with NoTx or pegIFN/RBV. Keywords: Hepatitis C, Chronic kidney disease, Economics, Elbasvir/grazoprevir

Xinyi Ng,1 Chizoba Nwankwo,2 Jean Marie Arduino,2 Shelby Corman,1 Kathryn Eilene Lasch,1 Jacqueline Mary Lustrino,1 Sushma Patel,2 Heather Loryn Platt,2 Jingjun Qiu,2 Jan Sperl3 1Pharmerit International, LP, Bethesda, MD, USA; 2Merck & Co. Inc., Kenilworth, NJ, USA; 3Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Purpose: People chronically infected with hepatitis C virus (HCV) have diminished patient-reported outcomes (PROs). This study aimed to compare the impact of elbasvir/grazoprevir (EBR/GZR) treatment versus sofosbuvir with pegylated interferon and ribavirin (SOF/PR) on changes in PROs: 1) during the treatment period and 2) at posttreatment follow-up. Patients and methods: PRO data collected during the Phase III C-EDGE Head-2-Head (H2H) open-label study was analyzed. In this trial, patients infected with HCV were randomized 1:1 to receive either EBR/GZR or SOF/PR for 12 weeks. Patients self-administered the Short Form-36 version 2 (SF-36v2®) Health Survey Acute (1-week recall) Form and the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale at baseline, during treatment, and posttreatment. Between-group differences in mean change of PRO scores from baseline were estimated during the treatment period and also at the posttreatment follow-up. Effect sizes were calculated to evaluate if the detected change in mean PRO scores is clinically meaningful between groups. Results: There were 255 patients (99.2% White, 54.1% female, 74.9% treatment naïve) included in the analysis. During the treatment period, significant declines in SF-36v2 scores were observed across all domains for the SOF/PR group. Compared to the SOF/PR group, the EBR/GZR group reported more improvement in scores across all SF-36v2 domain scores at the end of the treatment period. At treatment week 12, the between-group differences for 6 out of the 8 domain scores for these patients reflected at least moderate effects (effect sizes >0.5). No significant between-group differences in change in SF-36v2 scores from baseline were detected posttreatment. The decline in SF-36v2 scores observed during the treatment period for the SOF/PR group returned to near baseline scores or above posttreatment. Treatment with EBR/GZR did not impact fatigue scores, but treatment with SOF/PR led to increased fatigue scores during treatment which resolved by posttreatment follow-up week 12. Conclusion: This study demonstrated that HCV treatment with EBR/GZR resulted in a significantly better PRO profile as compared to SOF/PR. PROs are an important consideration as worsening PROs experienced during treatment may negatively influence adherence and ultimately contribute to an unfavorable clinical outcome. Clinical trials.gov Identifier: NCT02358044 Keywords: hepatitis, direct-acting antivirals, health-related quality of life, fatigue, patient-reported outcomes

Objective 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. Design 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. Patients 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. Intervention Fixed-dose combination of direct-acting antiviral agents elbasvir and grazoprevir compared to no-treatment. Results 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. Conclusions 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-naive 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.