Hepatitis C Drug Combination Shows Strong Efficacy With or Without Cirrhosis

Direct-acting-antiviral drugs daclatasvir, asunaprevir, and beclabuvir showed high rates of sustained virologic response after 12 weeks.

Direct-acting-antiviral drugs daclatasvir, asunaprevir, and beclabuvir showed high rates of sustained virologic response after 12 weeks.

A combination of direct-acting antiviral drugs reached high rates of sustained virologic response after 12 weeks (SVR12) in patients with chronic hepatitis C virus (HCV) genotype 1 infection with or without cirrhosis in a pair of recent studies.

A study led by Fred Poordad, MD, of the University of Texas Health Science Center, examined SVR rates in patients receiving a twice-daily combination of daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO regimen). The study included 312 treatment-naive patients and 103 patients previously treated for HCV genotype 1 who did not have cirrhosis.

The results of the study found that 379 of the 415 patients achieved SVR12 (91.3%), including 287 of 312 treatment-naive patients (92%) and 92 of 103 treatment-experienced patients (89.3%). Virologic failure was observed in 8% of patients.

There were 7 serious adverse events reported that were not related to treatment, with 3 adverse events causing treatment discontinuation. The most common adverse events reported were headache, fatigue, diarrhea, and nausea.

"This study demonstrates that 12 weeks of therapy with the DCV-TRIO regimen without ribavirin was associated with high rates of SVR12 in patients with HCV genotype 1 infection," the study authors wrote.

A second study led by Andrew J. Muir, MD, of the Duke University Medical Center, evaluated the efficacy the DCV-TRIO regimen in both treatment-naive and treatment-experienced patients with chronic HCV genotype 1 infection and cirrhosis.

The patients received the 3-drug combination regimen for 12 weeks with 24 weeks of follow-up after treatment was completed. Included were 112 patients with cirrhosis in an HCV treatment-naive cohort and 90 patients in an HCV treatment-experienced cohort.

The patients in each group were stratified according to HCV genotype 1 subtype (1a or 1b) and randomly received weight-based ribavirin (1000-1200 mg/d) or matching placebo. In the treatment-naive cohort, SVR12 was achieved by 93% of patients receiving the DCV-TRIO alone and by 98% of patients with ribavirin added.

In the treatment-experienced cohort, 87% of patients receiving DCV-TRIO alone achieved SVR 12, while 93% of patients achieved SVR 12 with ribavirin added. SVR12 was achieved by 51 of 52 patients with genotype 1b infection overall, while patients with genotype 1a achieved SVR12 rates of 86% to 97% across all treatment groups.

The results indicated that the benefits of ribavirin to SVR12 is still uncertain due to the small sample sizes, however adding ribavirin to the regimen for patients with genotype 1a infection should be considered.

"Despite the progress and the success of viral eradication, numerous questions remain unanswered such as response based on race, still difficult-to-treat situations such as patients with end-stage liver disease or undergoing hemodialysis, access to and affordability of these therapies, improvement in quality of life, and cost-effectiveness. It is time to reflect on these challenges and find solutions because the influence of HCV infection on global society is an ongoing challenge,” wrote Hari Conjeevaram, MD, MSc, in an accompanying editorial. "Despite the progress and the success of viral eradication, numerous questions remain unanswered such as response based on race, still difficult-to-treat situations such as patients with end-stage liver disease or undergoing hemodialysis, access to and affordability of these therapies, improvement in quality of life, and cost-effectiveness. It is time to reflect on these challenges and find solutions because the influence of HCV infection on global society is an ongoing challenge."