High sustained virologic response rates were seen among patients with decompensated cirrhosis in European compassionate care cohort.
A combination of daclatasvir plus sofosbuvir with or without ribavirin leads to high sustained virologic response at post-treatment week 12 (SVR12) in a diverse cohort of patients infected with hepatitis C virus (HCV) with severe liver disease, according to a new study.
Direct-acting antivirals (DAAs) have become the standard of care for treating chronic HCV infection, with clinical trials showing SVR12 rates that exceed 90%. However, patients with advanced liver disease and concomitant medical conditions are usually under-represented in clinical trials, stated researchers led by Tania M Welzel, MD of the Johann Wolfgang Goethe University in Frankfurt am Main, Germany. This population is less likely to respond satisfactorily to treatment and may suffer more frequent treatment-related adverse events, they noted.
Welzel and colleagues conducted a study in a real-world setting that included 485 adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options who were treated in a European compassionate use program.
The recommended regimen was daclatasvir 60 mg plus sofosbuvir 400 mg for 24 weeks. Ribavirin was allowed to be added at physicians' discretion. The primary endpoint was SVR12. Some 359 patients received daclatasvir plus sofosbuvir and 126 patients the two-drug combination plus ribavirin.
The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%); 80% of patients had cirrhosis.
The results show 91% of patients achieved SVR12; one patient had virologic breakthrough and 13 patients relapsed. Virologic failure was not associated with treatment group. “Similarly, high SVR12 rates were observed in patient subgroups with characteristics regarded as more difficult to cure, such as decompensated cirrhosis and genotype 3 infection with cirrhosis,” the authors stated, as well as those who had liver transplants or HIV/HCV coinfection.
Consistent with previous studies, the SVR12 rate was lower in patients with Child–Pugh C. Indicators of advanced liver disease, such as low platelet count or low albumin level, were associated with increased risk of failure, however, much of this was related to pre-existing advanced liver disease rather than to inadequate virologic efficacy, they stated.
Treatment with or without ribavirin had no significant effect on the probability of virologic failure. “Comparably high SVR12 rates were achieved with ribavirin (88%) and without ribavirin (89%),” the researchers stated.
Overall, daclatasvir plus sofosbuvir with or without ribavirin was well tolerated and was associated with improvements in liver function. Twenty-eight patients discontinued treatment due to adverse events (18 patients) or death (10 patients), and 18 patients died during follow-up. Most serious adverse events and treatment discontinuations were attributable to continued disease progression and not considered related to treatment.
The researchers stated “this cohort represents one of the largest cohorts of patients with advanced liver disease treated with an oral DAA combination in a real-world setting. The findings are consistent with the results of clinical trials evaluating daclatasvir plus sofosbuvir with or without ribavirin despite the inclusion of a broad spectrum of patients.”
The researchers published their results on September 7, 2016 in Gut.