Hepatitis C genotype 1 patients, with or without cirrhosis, show high rates of response to combination therapy

by Bruce Sylvester: Researchers from two newly published studies patients report that patients with chronic hepatitis C virus (HCV) genotype 1 infection and with or without cirrhosis have achieved high rates of sustained virologic response after 12 weeks of treatment with combination daclatasvir, asunaprevir, and beclabuvir.

The studies appeared on May 5, 2015 in JAMA/Journal of the American Medical Association

“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,” said Hari Conjeevaram, M.D., associate professor of medicine at the University of Michigan, Ann Arbor, in an accompanying editorial.

In one study, investigators evaluated rates of sustained virologic response (SVR) in subjects receiving a twice-daily combination of daclatasvir, asunaprevir and beclabuvir (DCV-TRIO regimen).

The study, UNITY-1, was conducted in the United States, Canada, France, and Australia.

The researchers enrolled both treatment-naïve subjects (n = 312) and those who had been treated previously (n = 103). Both cohorts had HCV genotype 1 infection and did not have cirrhosis. They defined sustained virologic response was as HCV-RNA <25 IU/ml at post-treatment week 12 (SVR12).

The investigators reported SVR12 was in 379 of 415 subjects (91.3 percent), in 287 of 312 treatment-naive subjects (92 percent) and 92 of 103 treatment-experienced subjects (89.3 percent).

One patient died at post-treatment week 3, from causes appearing to be unrelated to treatment.

Subjects reported 7 serious adverse events, and they were deemed to be unrelated to treatment. There were 3 adverse events (<1 percent) which led to discontinuation of treatment. Headache, fatigue, diarrhea, and nausea were the most common adverse events.

“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 concluded.

In a second study, UNITY-2, researchers studied the effectiveness of treatment with daclatasvir, asunaprevir, and beclabuvir in subjects with chronic HCV genotype 1 infection and cirrhosis.

The study was conducted in the United States, Canada, France and Australia.

Treatment took place for 12 weeks with the 3-drug combination regimen, followed by 24 weeks of follow-up observation.

The investigators enrolled subjects with cirrhosis into 2 cohorts, HCV treatment-naive or HCV treatment-experienced.

They stratified the subjects in each cohort according to HCV genotype 1 subtype (1a or 1b). They randomized the subjects to receive either weight-based ribavirin (1,000-1,200 mg/d) or matching placebo.

They included in the analysis 112 subjects in the treatment-naive group and 90 subjects in the treatment-experienced group.

Among the treatment-naive subjects, 93 percent treated with DCV-TRIO alone achieved sustained virologic response at post-treatment week 12 (SVR12). And 98 percent of subjects who also received ribavirin achieved sustained virologic response at post-treatment week 12 (SVR12).

SVR12 rates for the treatment­ experienced group were 87 percent for those receiving DCV-TRIO alone and 93 percent for patients for those who also received ribavirin.

Overall, subjects with genotype 1b infection achieved SVR12 at a rate of 98 percent (51 of 52 subjects).

SVR12 rates among subjects with genotype 1a were 86 percent to 97 percent across all treatment cohorts.

There were 3 serious adverse events considered to be treatment related. There were 4 adverse event related discontinuations of treatment.

The authors emphasized that the effect of ribavirin on SVR12 remains uncertain due to small sample sizes. However, they said, their results suggest that including ribavirin in the treatment regimen may be considered for patients with genotype 1a infection.

An estimated 130 million to 150 million persons worldwide are chronically infected with HCV, resulting in up to 350,000 deaths annually. Genotype 1 accounts for about 60 percent of the infections.