SAN FRANCISCO, CA—Baseline hepatitis C virus (HCV) RNA levels (>800,000 IU/mL) and baseline NS5A resistance-associated variants (RAVs) predict sustained virologic response 12 weeks after therapy ends (SVR12) among patients with treatment-naïve genotype 1a (GT1a) hepatitis C virus (HCV) infection treated with grazoprevir/elbasvir (Zepatier; Merck) with or without ribavirin, concluded authors of a study presented at The Liver Meeting® 2015.
An “important interaction” was noted between baseline HCV RNA and NS5A RAVs, the study authors emphasized.
“A significant impact was observed only in patients with both factors,” noted Stefan Zeuzem, MD, of the J.W. Goethe University Hospital, Frankfurt, Germany, and colleagues. “Neither of these factors predicted SVR12 in GT1b-infected treatment-naïve patients,” he noted.
“Among GT1a-infected patients, female patients and non-cirrhotics had numerically higher SVR12 rates, and the addition of ribavirin and/or longer treatment duration had a positive impact on SVR12,” he added. “The addition of ribavirin to the regimen does not increase SVR12 in GT1a or GT1b-infected treatment-naïve patients.”
Grazoprevir 100mg plus elbasvir 50mg, with or without ribavirin, is highly effective among patients with HCV GT1 infection, with up to 95% achieving an SVR12 in Phase 2/3 clinical trials. However, these same trials showed that 3% of patients with GT1 experienced virologic failure. Therefore, the goal of this study was to assess potential predictors of response to therapy.
Dr. Zeuzem and colleagues performed analyses on 2 pooled datasets of patients with GT1-infection enrolled in Phase 2/3 trials of grazoprevir/elbasvir with or without ribavirin. This included treatment-naïve patients and patients who previously had failed peginterferon + ribavirin with or without a first-generation protease inhibitor.
“Univariate logistic regression models were fitted one variable at a time in assessing the potential association with SVR12,” he explained. Subsequently, multivariable logistic regression models with forward selection were applied to identify significant independent predictors of SVR12, defined as P<0.1.
The multivariable logistic regression models found that among patients who were treatment-naïve, “age, sex, cirrhosis, HIV co-infection, baseline NS3 RAVs, and use of ribavirin did not impact SVR12 rates,” he reported.
Among patients with GT1b-infection, no significant predictors were identified. Among those who had previously failed peginterferon plus ribavirin plus a first-generation protease inhibitor, “no significant predictors were identified for GT1b-infected patients or in GT1a-infected patients with prior relapse,” the authors noted.
L31M and Y93H were the most prevalent RAVs. Baseline NS5A >5× RAVs, which were detected in 8% of treatment-experienced GT1a-infected patients, had a significant negative impact on SVR12. This impact was confined to the 12 weeks of treatment. No patient treated with ribavirin for 16 or 18 weeks experienced virologic failure.