Author(s): Zeuzem S, Ghalib R, Reddy KR, Pockros PJ, Ben Ari Z,
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Abstract BACKGROUND: Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. OBJECTIVE: To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients. DESIGN: Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467). SETTING: 60 centers in the United States, Europe, Australia, Scandinavia, and Asia. PATIENTS: Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection. INTERVENTION: Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy. MEASUREMENTS: Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups. RESULTS: Among 421 participants, 194 (46\%) were women, 157 (37\%) were nonwhite, 382 (91\%) had genotype 1 infection, and 92 (22\%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95\% [95\% CI, 92\% to 97\%]) achieved SVR12, including 144 of 157 (92\% [CI, 86\% to 96\%]) with genotype 1a, 129 of 131 (99\% [CI, 95\% to 100\%]) with genotype 1b, 18 of 18 (100\% [CI, 82\% to 100\%]) with genotype 4, 8 of 10 (80\% [CI, 44\% to 98\%]) with genotype 6, 68 of 70 (97\% [CI, 90\% to 100\%]) with cirrhosis, and 231 of 246 (94\% [CI, 90\% to 97\%]) without cirrhosis. Virologic failure occurred in 13 patients (4\%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8\%) and 3 (2.9\%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17\%), fatigue (16\%), and nausea (9\%). LIMITATION: The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections. CONCLUSION: Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection. PRIMARY FUNDING SOURCE: Merck & Co.
This article was published in Ann Intern Med
and referenced in Journal of Antivirals & Antiretrovirals