ObjectiveTo 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.DesignThis 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.PatientsThe 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.InterventionFixed-dose combination of direct-acting antiviral agents elbasvir and grazoprevir compared to no-treatment.ResultsEBR/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.ConclusionsThis 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.

Recipients of allogeneic hematopoietic stem cell transplant (HSCT) who have positive cytomegalovirus (CMV) serology are at increased risk for morbidity and mortality after HSCT. However, the exact correlation between early CMV infection and post-HSCT outcomes, notably relapse, is still a source of conflicting data, especially in the era of viral surveillance through polymerase chain reaction (PCR) and preemptive antiviral therapy. We thus decided to retrospectively investigate the clinical impact of early, post-HSCT CMV infection/disease, in a large multi-center cohort of French patients. All consecutive CMV-seropositive adults (≥ 18 years old) who received a first HSCT in 3 French centers between January 1st 2010 and December 31th 2014 were eligible. Cord blood transplantation or a second HSCT were not considered here, as these procedures are associated with a significantly higher risk of morbidity and mortality. Study data were primarily derived from existing electronic health records. The study was conducted in accordance with the Declaration of Helsinki. CMV infection/disease was defined by the initiation of a preemptive and/or a curative anti-CMV treatment in the presence of a CMV viremia detected by a quantitative PCR. The primary objective of this study was to assess the association between CMV infection/disease and overall mortality within the first-year post-transplantation. Secondary clinical endpoints addressed the association between CMV infection/disease and the following outcomes within the first-year of HSCT: graft failure, relapse of the underlying disease, non-relapse mortality (NRM), incidence of acute and chronic graft-versus-host disease (GvHD), and the occurrence of infections other than CMV. Relapse was considered as a competing risk for non-relapse mortality, and death for other events of interest (relapse, incidence of acute and chronic GvHD, and occurrence of infections). Models were adjusted for disease type, disease status at HSCT, age at HSCT, sex, donor type, stem cell source, and conditioning regimen (MAC versus RIC, use of total body irradiation or anti-thymocyte globulin). Five hundred seventy-two patients (54.5% male, 71.2% with Karnofsky >90, and median age 54 years) met the inclusion criteria. Underlying diseases were acute leukemia (33.9%), lymphoid neoplasms (25.9%), and myelodysplastic/ myeloproliferative neoplasms (22.6%). The disease was generally in complete remission at the time of HSCT (56.5%) or stable at the time of HSCT (16.4%). The majority of patients had received a reduced intensity conditioning regimen HSCT (72.5%), and peripheral blood stem cells (71.3%). Donor type was as follows: HLA-matched unrelated donor, 34.1%; HLA-matched relative donor, 46.5%; mismatched unrelated donor, 16.3% and mismatched related donor, 3.10%. CMV infection/disease was observed in 227 patients (39.7%) at a median time of 39.5 days (range, 3-295 days) post-transplant. Overall survival rate as per Kaplan-Meier analysis was 70.9% at 1-year post-HSCT. After adjusting for significant risk factors and considering CMV infection/disease as a time-dependent variable in a Cox model, overall mortality at 1-year was significantly increased in patients developing CMV infection/disease (HR 1.86, [95%CI 1.16 - 3.00], p=0.011). The Fine and Gray competing risk model showed that CMV infection/disease during the first-year post-transplant was significantly associated with higher risk of infections other than CMV (HR 2.34, 95%CI [1.63 - 3.37], p<0.0001) and, consequently, an increased risk for NRM (HR 2.62, 95%CI [1.59 - 4.30], p=0.0001). We did not find any significant association between CMV infection/disease and acute or chronic GvHD, as well as with relapse. In this large cohort of 572 consecutive CMV-seropositive adults undergoing allo-HSCT, and who were monitored with a PCR-based strategy according to routine clinical practice, we identified that CMV infection/disease were significantly associated with an increased risk of 1-year overall and non-relapse mortality, related to higher rates of infections other than CMV. Therefore, post-HSCT CMV infection/disease seemed to be a major concern in the recent healthcare setting, affecting mortality and morbidity. Disclosures Peffault De Latour: Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer Inc.: Consultancy, Honoraria, Research Funding. Clement:MSD: Employment. Allavoine:MSD: Employment. Tadmouri:ClinSearch: Employment. Blomkvist:ClinSearch: Employment.

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being the cheapest with a total cost of 81.49V and the most effective with a total QALDs of 4.272. The total differential costs were +35.45V, +37.38V, +68.77V and +6.89V; the total differential QALDs were respectively -0.0004, -0.0001, -0.0004 and -0.0006 and the proportions of CINV-free patients at 5 days was 83.0% for NEPA and 79.4%, 83.0%, 79.1% and 75.5% for APR+OND, APR+PAL, FOS+GRA and ROL+GRA respectively. NEPA was also dominant against all three comparators in Greece, with a total cost of 85.00V. The differential total costs were +10.46V, +27.07V and +23.05V for APR+OND, APR+PAL and FOS+GRA respectively. CONCLUSIONS: NEPA is a cost-effective strategy for prevention of CINV in patients undergoing HEC in both Germany and Greece.