CHICAGO – Oral sofosbuvir and ribavirin given for 12 weeks produced a sustained virologic response in 93% of 250 patients with hepatitis C virus genotype 2 and in 85% of patients with genotype 3 infection who were treated for 24 weeks.
The 77-center European study defined a sustained virologic response as a hepatitis C virus RNA level of less than 25 IU/mL, Dr. Stefan Zeuzem and his associates reported. More than half of the patients (58%) had undergone prior therapy with interferon-based regimens, with no response in 30%. Cirrhosis was present in 21% of patients.
The study began as a phase III trial randomizing patients to receive 12 weeks of once-daily oral sofosbuvir 400 mg and twice-daily oral ribavirin (administered according to body weight), or matching placebo. The investigators turned the trial into a descriptive study after a previous study reported that patients with genotype 3 infection might benefit from more than 12 weeks of sofosbuvir therapy (N. Engl. J. Med. 2013;368:1867-77).
Dr. Zeuzem and his associates unblinded the treatment arms, dropped placebo treatment, and extended treatment for patients with genotype 3 infection to 24 weeks. The findings were published online in the New England Journal of Medicine (N. Engl. J. Med. 2014 May 4 [doi: 1056/NEJMoa1316145]).
Among patients with genotype 3 infection, a sustained virologic response developed in 68% of those with cirrhosis and 91% without cirrhosis, reported Dr. Zeuzem, who is professor of medicine and chief of the department of medicine I at Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany.
Headache, fatigue, and pruritus were the most common adverse events. Approximately 1% of patients in both the genotype 3 and 4 groups discontinued treatment due to side effects.
Treatment history and the presence of cirrhosis affected response rates in patients with genotype 3 infection. In previously untreated patients, a sustained virologic response was seen in 92% of those with cirrhosis and in 95% without cirrhosis. Response rates were lower in previously treated patients with cirrhosis (62%) and without cirrhosis (87%). The reasons for these differences are unknown.
Four factors were independently associated with a sustained virologic response in patients with genotype 3 infection, a multivariate regression analysis found. A sustained response was four times as likely in those with a baseline hepatitis C virus RNA level of less than 6 log10 IU and three times as likely in women, patients without cirrhosis, or those under age 50, compared with patients without those characteristics. These predictive factors must be validated in further studies, Dr. Zeuzem said.
Three patients with genotype 3 infection had a virologic relapse. The response rate and relapse rate for patients with genotype 3 who were treated for 24 weeks were "substantially" better than rates reported in previous studies using the same regimen for 12 or 16 weeks, the investigators said. Extending the duration of treatment did not significantly increase adverse events or discontinuation of therapy.
The findings suggest that sofosbuvir-ribavirin can be an alternative therapy for patients with hepatitis C virus genotype 2 or 3 who have contraindications to peginterferon-based treatment, Dr. Zeuzem said.
Gilead Sciences, which markets sofosbuvir, funded the study. Dr. Zeuzem reported financial associations with Gilead and multiple other pharmaceutical companies, as did many of his coinvestigators.
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