Safety & Efficacy of Boceprevir/Peginterferon/Ribavirin for HCV G1 Compensated Cirrhotics: Meta-Analysis of 5 Trials.
ABSTRACT HCV-infected cirrhotics may urgently need therapy but are often under-represented in clinical trials resulting in limited data to guide their management. We performed a meta-analysis of well-compensated cirrhotic patients from five Phase 3 trials.
Patients received P/R (peginterferon/ribavirin; 4 weeks) followed by BOC(boceprevir)/P/R or P/R for 24, 32 or 44 weeks. Sustained virologic response (SVR) rates were calculated by Metavir score. Multivariate logistic regression (MLR) models identified baseline and on-treatment predictors of SVR. Safety was evaluated by adverse-event (AE) reporting and laboratory monitoring.
Pooled meta-estimates for SVR rates (95% confidence interval) in 212 F4 (cirrhotic) patients were 55% (43, 66) with BOC/P/R vs.17% (0, 41) with P/R. MLR identified 4 predictors of SVR in F3/F4 patients: undetectable HCV-RNA at treatment week (TW) 8; ⩾1 log10 decline in HCV-RNA from baseline at TW4; male; and baseline HCV-RNA ⩽800,000 IU/mL. SVR rate was 89% (65/73) in F4 patients who were HCV-RNA undetectable at TW8. No F3(0/5) or F4(0/17) patients with <3 log10 decline and detectable HCV-RNA at TW8 achieved SVR. Anemia and diarrhea occurred more frequently in cirrhotic than non-cirrhotic patients. Serious AEs, discontinuations due to an AE, interventions to manage anemia, infections and thrombocytopenia occurred more frequently in cirrhotics with BOC/P/R than P/R. Potential hepatic decompensation and/or sepsis were identified in 2 P/R and 3 BOC/P/R recipients.
BOC/P/R appears to have a generally favorable benefit-risk profile in compensated cirrhotic patients. SVR rates were particularly high in cirrhotic patients with undetectable HCV-RNA at TW8.
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ABSTRACT: Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable.PLoS ONE 04/2015; 10(4):e0125080. DOI:10.1371/journal.pone.0125080 · 3.53 Impact Factor
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ABSTRACT: Significant attention has been focused on the perceived increase in the cost of antiviral treatment for hepatitis C genotype 1 infection since the approval of the first direct-acting antiviral agents in 2011. Using Canadian list prices, the present analysis points out a paradox: while the cost per antiviral regimen is increasing, the cost per cure is decreasing, especially with interferon-free therapy. In a publicly funded health care system, the lowest cost per cure is a more valuable measure of value for public money than the cost per regimen.
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ABSTRACT: Introduction: IFN-free regimens with direct antiviral agents (DAAs) against hepatitis C virus (HCV) are likely to greatly expand patients' access and response to hepatitis C therapy, while safety and tolerability of treatments seem substantially improved. Sofosbuvir (SOF), a NS5B nucleotide polymerase inhibitor with pan-genotypic activity and a high-barrier to resistance, has been approved by FDA and EMA in an all oral combination therapy for chronic hepatitis C with ribavirin (RBV) alone, or in combination with either pegylated interferon/RBV or other DAAs. Areas covered: This paper provides an overview of SOF-based therapy in chronic hepatitis C as it emerges from the published clinical trials. Data on special populations are included (i.e., decompensated patients, patients on liver transplant waiting lists, patients with renal impairment). The data has been analyzed according to the different HCV-genotypes and comprehensively covers both safety and efficacy treatment profiles. Expert opinion: Clinical trials have highlighted the safety and efficacy of SOF-based regimens, leading to the rapid approval of this therapy and its incorporation in the recommendations of the international societies on treatment of HCV infection. However, additional data are still needed to optimize both combination therapies' efficacy and duration in some categories of patients who have been under-represented in the registration trials.Expert Opinion on Drug Safety 02/2015; 14(3):1-12. DOI:10.1517/14740338.2015.1009035 · 2.74 Impact Factor