Daclatasvir and Peginterferon/Ribavirin for Black/African-American and Latino Patients with HCV infection

• Main Authors: Maribel Rodriguez-Torres, Eric Läwitz, Bienvenido Yangco, Lennox Jeffers, Steven-Huy Han, Paul J. Thuluvath, Vinod Rustgi, Stephen Harrison, Reem Ghalib, John M. Vierling, Velimir Luketic, Philippe J. Zamor, Natarajan Ravendhran, Timothy R. Morgan, Brian Pearlman, Christopher O’Brien, Hicham Khallafi, Nikolaos Pyrsopoulos, George Kong, Fiona McPhee, Philip D. Yin, Eric Hughes, Michelle Treitel
• Format: Article
• Language: English
• Published: Elsevier 2016-11-01
• Series: Annals of Hepatology
• Subjects: NS5A Inhibitor; Antiviral therapy; Liver disease; Ethnicity; Race
• Online Access: http://www.sciencedirect.com/science/article/pii/S1665268119311093

Background. Patient race and ethnicity have historically impacted HCV treatment response. This phase 3 study evaluated daclatasvir with peginterferon-alfa-2a/ribavirin (pegIFN alfa-2a/RBV) in treatment-naive black/African American (AA), Latino, and white non-Latino patients with chronic HCV genotype 1 infection.Material and methods. In this single-arm, open-label study, 246 patients received daclatasvir plus pegIFN alfa-2a and weight-based RBV. Patients with an extended rapid virologic response (eRVR; undetectable HCV-RNA at treatment weeks 4 and 12) received 24 weeks of treatment; those without eRVR received an additional 24 weeks of treatment with pegIFN alfa-2a/RBV. The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12; HCV-RNA < 25 IU/mL) compared with the cohort historical rate.Results. Most patients were IL28B non-CC (84.4% black/AA; 77.6% Latino) genotype 1a-infected (72.7%; 81.3%), with HCV-RNA ≥ 800,000 IU/mL (81.3%; 64.5%). SVR12 rates were 50.8% (65/128; 95% confidence interval [CI], 42.1-59.4) for black/AA and 58.9% (63/107; 95% CI, 49.6-68.2) for Latino patients. The majority (55.5%; 58.9%) received 24 weeks treatment; rapid reductions (> 4-log10) in HCV-RNA levels were observed. Only 60.9% (78/128) of black/AA and 63.6% (68/107) of Latino patients completed treatment. On-treatment serious adverse events (SAEs) occurred in 21 patients. Discontinuations due to adverse events (aEs) occurred in 9 black/AA and 6 Latino patients.Conclusion. SVR12 rates for black/AA (50.8%) and Latino (58.9%) cohorts treated with daclatasvir plus pegIFN alfa-2a/RBV and the lower bound of the 95% Cls were higher than the estimated historical control (black/AA, 26% SVR; Latino, 36% SVR) treated with pegIFN alfa-2a/RBV. These data support daclatasvir use in all-oral direct-acting antiviral combinations.