Published in Journal Watch Gastroenterology May 24, 2013
Two phase III studies confirm the efficacy of a sofosbuvir and ribavirin therapy in patients with HCV genotype 2 or 3 infection for whom peginterferon is not an option.
In patients infected with hepatitis C virus (HCV) genotype 2 or 3, treatment with peginterferon plus ribavirin has a sustained virologic response (SVR) of 70% to 85%. However, adverse effects of peginterferon are a barrier to treatment for many patients. Now, two industry-funded, phase III trials have evaluated the efficacy of sofosbuvir (400 mg daily) plus ribavirin (1000 mg–1200 mg daily) in these patients.
In a blinded, placebo-controlled trial, investigators randomized 280 patients for whom peginterferon therapy was not an option (e.g., adverse effects, contraindications for interferons, and patient refusal) to receive sofosbuvir/ribavirin or matching placebo for 12 weeks. In a blinded, active-control trial, researchers randomized 202 patients with prior nonresponse to peginterferon therapy to receive 12 or 16 weeks of sofosbuvir/ribavirin. The primary endpoint in both studies was SVR at 12 weeks after therapy ended.
In patients for whom peginterferon therapy was not an option, SVR was 78% for treatment with sofosbuvir/ribavirin compared with 0% for placebo (P<0.001). In previously treated patients, SVR was 50% for 12 weeks of therapy versus 73% for 16 weeks (P<0.001). SVR rates were lower for patients with genotype 3 versus genotype 2 in both treatment-naive patients (61% vs. 93%) and treatment-experienced patients who received therapy for 12 weeks (30% vs. 86%) or 16 weeks (62% vs. 94%).
SVR rates were lower in patients with cirrhosis than without, both in treatment-naive patients (overall, 61% vs. 81%; genotype 3 vs. 2, 21% vs. 94%) and treatment-experienced patients (overall, 66% vs. 76%; genotype 3 vs. 2 in 16-week group, 61% vs. 78%). In both studies, investigators found no evidence of resistance development, and discontinuation rates were low (1%–2%).
Comment: Oral sofosbuvir plus ribavirin is effective in patients with HCV genotypes 2 or 3 for whom peginterferon-based therapy is not an option or was previously ineffective. Of note, these sustained virologic response rates for sofosbuvir plus ribavirin are comparable to or higher than those previously reported for therapy with peginterferon plus ribavirin in this population.
Jacobson IM et al. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med 2013 May 16; 368:1867. (http://dx.doi.org/10.1056/NEJMoa1214854)
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