Studies show effectiveness of combo treatment for HCV patients with, without cirrhosis
In two studies appearing in the May 5 issue of JAMA, patients with chronic hepatitis C virus (HCV) genotype 1 infection and with or without cirrhosis achieved high rates of sustained virologic response after 12 weeks of treatment with a combination of the direct-acting-antiviral drugs daclatasvir, asunaprevir, and beclabuvir.
Current estimates indicate that 130 million to 150 million people worldwide are chronically infected with HCV, resulting in up to 350,000 deaths per year. Of the 7 HCV genotypes identified, genotype 1 is the most prevalent worldwide, accounting for approximately 60 percent of infections. Treatment options for HCV genotype 1 are evolving rapidly from interferon-based regimens to all-oral, direct-acting antiviral only regimens.
In one study, Fred Poordad, M.D., of the University of Texas Health Science Center, San Antonio, Texas, and colleagues determined the rates of sustained virologic response (SVR) in patients receiving a twice-daily combination of daclatasvir, asunaprevir and beclabuvir (DCV-TRIO regimen). The study included both treatment-naive (n = 312) and patients who had previously received treatment (n = 103) for HCV genotype 1 infection and who did not have cirrhosis. This international study (UNITY-1) was conducted at 66 sites in the United States, Canada, France, and Australia. Sustained virologic response was defined as HCV-RNA <25 IU/ml at post-treatment week 12 (SVR12).
Overall, SVR12 was observed in 379 of 415 patients (91.3 percent): 287 of 312 treatment-naive patients (92 percent) and 92 of 103 treatment-experienced patients (89.3 percent). Virologic failure occurred in 8 percent of patients.
One patient died at post-treatment week 3: this was not considered related to study medication. There were 7 serious adverse events, all considered unrelated to study treatment, and 3 adverse events (<1 percent) leading to treatment discontinuation. The most common adverse events (in ? 10 percent of patients) 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 authors write.
In another study, Andrew J. Muir, M.D., of the Duke University Medical Center, Durham, N.C., and colleagues evaluated the effectiveness of treatment with daclatasvir, asunaprevir, and beclabuvir in patients who were treatment-naive and treatment-experienced with chronic HCV genotype 1 infection and cirrhosis.
An estimated 20 percent of patients with chronic HCV infection will develop cirrhosis, with the prevalence increasing. Patients with cirrhosis are at increased risk for liver cancer and death. Effective and well-tolerated, interferon-free regimens are needed for these patients.
This study (UNITY-2) was conducted at 49 outpatient sites in the United States, Canada, France and Australia. Patients were treated for 12 weeks with the 3-drug combination regimen, with 24 weeks of follow-up after completion of treatment. Patients with cirrhosis were enrolled in 2 cohorts: HCV treatment-naive or HCV treatment-experienced; patients within each cohort were also stratified according to HCV genotype 1 subtype (1a or 1b) and randomly assigned to receive weight-based ribavirin (1,000-1,200 mg/d) or matching placebo.
One hundred twelve patients in the treatment-naive group and 90 patients in the treatment-experienced group were treated and included in the analysis. In the treatment-naive group, sustained virologic response at post-treatment week 12 (SVR12) was achieved by 93 percent of patients receiving DCV-TRIO alone and by 98 percent of patients with ribavirin added; and corresponding SVR12 rates for the treatment experienced group were 87 percent for patients receiving DCV-TRIO alone and 93 percent for patients with ribavirin added. SVR12 was achieved by 51 of 52 patients (98 percent) with genotype 1b infection overall; and SVR12 rates in patients with genotype 1a were 86 percent to 97 percent across all treatment groups.
Three serious adverse events were considered to be treatment related and there were 4 adverse event-related discontinuations.
The authors note that the contribution of ribavirin to SVR12 remains uncertain because of the small sample sizes; results suggest that inclusion of ribavirin with the regimen may be considered for patients with genotype 1a infection.
"In this open-label, uncontrolled study, patients with chronic HCV genotype 1 infection and cirrhosis who received a 12-week oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved high rates of SVR12."
"These 2 studies add to the armamentarium of all-oral interferon-free regimens that have revolutionized management of hepatitis C, not only for patients who are treatment naive with no significant liver disease but also for those who are treatment experienced and those with cirrhosis," writes Hari Conjeevaram, M.D., M.Sc., of the University of Michigan, Ann Arbor, 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."
Paper 2: DOI: 10.1001/jama.2015.3868
Editorial: DOI: 10.1001/jama.2015.4368