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Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study.

ABSTRACT: SPRINT-2 demonstrated that boceprevir (BOC), an oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor, added to peginterferon alfa-2b (P) and ribavirin (R) significantly increased sustained virologic response rates over PR alone in previously untreated adult patients with chronic HCV genotype 1. We estimated the long-term impact of triple therapy vs. dual therapy on the clinical burden of HCV and performed a cost-effectiveness evaluation.A Markov model was used to estimate the incidence of liver complications, discounted costs (2010 US$), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) of three treatment strategies for treatment-naïve patients with chronic HCV genotype 1. The model simulates the treatment regimens studied in SPRINT-2 in which PR was administered for 4 weeks followed by: 1) placebo plus PR for 44 weeks (PR48); 2) BOC plus PR using response guided therapy (BOC/RGT); and 3) BOC plus PR for 44 weeks (BOC/PR48) and makes projections within and beyond the trial. HCV-related state-transition probabilities, costs, and utilities were obtained from previously published studies. All costs and QALYs were discounted at 3%.The model projected approximately 38% and 43% relative reductions in the lifetime incidence of liver complications in the BOC/RGT and BOC/PR48 regimens compared with PR48, respectively. Treatment with BOC/RGT is associated with an incremental cost of $10,348 and an increase of 0.62 QALYs compared to treatment with PR48. Treatment with BOC/PR48 is associated with an incremental cost of $35,727 and an increase of 0.65 QALYs compared to treatment with PR48. The ICERs were $16,792/QALY and $55,162/QALY for the boceprevir-based treatment groups compared with PR48, respectively. The ICER for BOC/PR48 compared with BOC/RGT was $807,804.The boceprevir-based regimens used in the SPRINT-2 trial were projected to substantially reduce the lifetime incidence of liver complications and increase the QALYs in treatment-naive patients with hepatitis C genotype 1. It was also demonstrated that boceprevir-based regimens offer patients the possibility of experiencing great clinical benefit with a shorter duration of therapy. Both boceprevir-based treatment strategies were projected to be cost-effective at a reasonable threshold in the US when compared to treatment with PR48.

SUBMITTER: Ferrante SA

PROVIDER: S-EPMC3643851 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study.

Ferrante Shannon Allen SA Chhatwal Jagpreet J Brass Clifford A CA El Khoury Antoine C AC Poordad Fred F Bronowicki Jean-Pierre JP Elbasha Elamin H EH

BMC infectious diseases 20130427

<h4>Background</h4>SPRINT-2 demonstrated that boceprevir (BOC), an oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor, added to peginterferon alfa-2b (P) and ribavirin (R) significantly increased sustained virologic response rates over PR alone in previously untreated adult patients with chronic HCV genotype 1. We estimated the long-term impact of triple therapy vs. dual therapy on the clinical burden of HCV and performed a cost-effectiveness evaluation.<h4>Methods</h4>A Marko ...[more]

PMID: 23621902

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Project description:BackgroundPeginterferon-ribavirin therapy is the current standard of care for chronic infection with hepatitis C virus (HCV). The rate of sustained virologic response has been below 50% in cases of HCV genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has been evaluated as an additional treatment in phase 1 and phase 2 studies.MethodsWe conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were randomly assigned to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (the control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks. Nonblack patients and black patients were enrolled and analyzed separately.ResultsA total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 (P<0.001), and in 213 of the 311 patients (68%) in group 3 (P<0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (P=0.04), and in 29 of the 55 patients (53%) in group 3 (P=0.004). In group 2, a total of 44% of patients received peginterferon-ribavirin for 28 weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively.ConclusionsThe addition of boceprevir to standard therapy with peginterferon-ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24 weeks and 44 weeks of boceprevir. (Funded by Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov number, NCT00705432.).

Project description:In patients with chronic infection with hepatitis C virus (HCV) genotype 1 who do not have a sustained response to therapy with peginterferon-ribavirin, outcomes after retreatment are suboptimal. Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site, has been suggested as an additional treatment.To assess the effect of the combination of boceprevir and peginterferon-ribavirin for retreatment of patients with chronic HCV genotype 1 infection, we randomly assigned patients (in a 1:2:2 ratio) to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 32 weeks, and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon-ribavirin for an additional 12 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks.A total of 403 patients were treated. The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, P<0.001). Among patients with an undetectable HCV RNA level at week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients with a decrease in the HCV RNA level of less than 1 log(10) IU per milliliter at treatment week 4, the rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively. Anemia was significantly more common in the boceprevir groups than in the control group, and erythropoietin was administered in 41 to 46% of boceprevir-treated patients and 21% of controls.The addition of boceprevir to peginterferon-ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon-ribavirin alone. (Funded by Schering-Plough [now Merck]; HCV RESPOND-2 ClinicalTrials.gov number, NCT00708500.).

Project description:Boceprevir (Victrelis), from the oral ?-ketoamide class of slow-binding reversible hepatitis C virus (HCV)-NS3 protease inhibitors, creates a new class of drugs: direct acting antivirals (DDAs). Boceprevir is highly selective against HCV serine protease. Its use is restricted to genotype 1 HCV infection and it must not be used as monotherapy. Boceprevir is given orally, rapidly absorbed, reaching plasma peak concentration within 1-2 h and is metabolized by aldo-ketoreductase and partly by the cytochrome P450 enzyme CYP3A4/5. Administration with drugs that induce or inhibit CYP3A4/5 could decrease or increase its plasma concentration. The optimal dosage is 800 mg three times daily; capsules should be taken with food. Boceprevir was approved by the US Food and Drug Administration and the European Medicines Agency and is indicated in combination with peginterferon plus ribavirin for the treatment of patients with genotype 1 HCV who have not received previous treatment or whose condition has failed to respond to previous therapy. In the Serine Protease Inhibitor Therapy 2 (SPRINT-2) trial (treatment-naïve patients) and RESPOND-2 trial (patients whose condition relapsed or did not respond to previous treatment), the boceprevir-containing regimen was always more effective than standard of care (SOC). Adverse events were similar in the treatment groups, but in the boceprevir treated group, anemia was more frequent, requiring erythropoietin in nearly 40% of cases. Discontinuation of therapy because of adverse events was identical in all treated groups. As for cost effectiveness, two studies showed that boceprevir plus SOC is cost effective with regard to the lifetime incidence of liver complications, quality of life years, and the incremental cost-effectiveness ratio. The management of this therapy is more complex than before for physicians and patients. The educational role of the physician is crucial for successful therapy and counseling should be carefully given, especially for adherence to the assigned treatment.

Project description:Background: Hepatitis C virus (HCV) genotype 1 is the most prevalent HCV infection in China. Sofosbuvir-based direct antiviral agent (DAA) regimens are the current mainstays of treatment. Sofosbuvir/velpatasvir (SOF/VEL) and sofosbuvir/ledipasvir (SOF/LDV) regimens became reimbursable in China in 2020. Thus, this study aimed to identify the optimal SOF-based regimen and to inform efficient use of healthcare resources by optimizing DAA use in treating HCV genotype 1. Methods and Models: A modeling-based cost-utility analysis was conducted from the payer's perspective targeting adult Chinese patients with chronic HCV genotype 1 infection. Direct medical costs and health utilities were inputted into a Markov model to simulate lifetime experiences of chronically infected HCV patients after receiving SOF/LDV, SOF/VEL or the traditional strategy of pegylated interferon (pegIFN) + ribavirin (RBV). Discounted lifetime cost and quality adjusted life years (QALYs) were computed and compared to generate the incremental cost utility ratio (ICUR). An ICUR below the threshold of 31,500 $/QALY suggests cost-effectiveness. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of model findings. Results: Both SOF/LDV and SOF/VEL regimens were dominant to the pegIFN + RBV regimen by creating more QALYs and incurring less cost. SOF/LDV produced 0.542 more QALYs but cost $10,390 less than pegIFN + RBV. Relative to SOF/LDV, SOF/VEL had an ICUR of 168,239 $/QALY which did not meet the cost-effectiveness standard. Therefore SOF/LDV was the optimal strategy. These findings were robust to linear and random variations of model parameters. However, reducing the SOF/VEL price by 40% would make this regimen the most cost-effective option. Conclusions: SOF/LDV was found to be the most cost-effective treatment, and SOF/VEL was also economically dominant to pegIFN + RBV. These findings indicated that replacing pegIFN + RBV with DAA regimens could be a promising strategy.

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Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study.

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Boceprevir for previously untreated patients with chronic hepatitis C Genotype 1 infection: a US-based cost-effectiveness modeling study.

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