Sofosbuvir + peginterferon/ribavirin for 12 weeks vs sofosbuvir + ribavirin for 16 or 24 weeks in genotype 3 HCV infected patients and treatment-experienced cirrhotic patients with genotype 2 HCV: The BOSON study. [Journal of Hepatology]

Abstract

Introduction: Sofosbuvir (SOF) in combination with ribavirin with or without peginterferon (PEG) has demonstrated high efficacy in genotype 2 or 3 HCV-infected patients. However, these regimens have not been directly compared. The phase 3 BOSON study evaluated the safety and efficacy of SOF+PEG/RBV for 12 weeks vs SOF+RBV for 16 or 24 weeks in treatment-experienced genotype 2 (GT2) HCV-infected patients with cirrhosis, and in treatment-naive and -experienced genotype 3 (GT3) HCV-infected patients with and without cirrhosis. Material(s) and Method(s): Patients were randomized 1:1:1 to receive either SOF+RBV for 16 or 24 weeks or SOF+PEG/RBV for 12 weeks and stratified by HCV genotype and cirrhosis status. All patients received SOF 400mg daily and RBV 1000-1200mg in a divided daily dose. PEG was administered as 180 mug weekly injection. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). Result(s): Of 592 patients randomized and treated, 92% had GT3 HCV, 67% were male, 84% white, 53% treatment experienced, 62% had non-CC IL28B genotypes, and 37% had cirrhosis. GT2 treatmentexperienced patients with cirrhosis had high SVR12 rates in all treatment groups: 87% of those receiving SOF+RBV for 16 weeks, 100% of those receiving SOF+RBV for 24 weeks, and 94% of those receiving SOF+PEG/RBV for 12 weeks. Among GT3 patients, SVR12 rates were highest in those receiving SOF+PEG/RBV for 12 weeks (93%) as compared to SOF+RBV for 24 (84%, p 0.008) or 16 weeks (71%, p < 0.001) (Table). The most common adverse events in all arms were fatigue, headache, insomnia, and nausea. Overall, 6 (1%) patients discontinued treatment due to adverse events; one of them was treated with SOF+PEG/RBV. (Table Presented) Conclusion(s): GT2 treatment-experienced patients with cirrhosis had high SVR12 rates in all treatment arms. In GT3 patients, including a large proportion of treatment-experienced patients with cirrhosis, SOF+PEG/RBV for 12 weeks resulted in the highest SVR12 rates observed to date in a Phase 3 study. Overall and in all subgroups, GT3 patients receiving 24 weeks of SOF+RBV had higher SVR12 rates than those receiving 16 weeks of treatment, confirming that 24 weeks is the optimal duration for this combination in GT3 patients. SOF+PEG/RBV for 12 weeks was well tolerated with a high rate of treatment completion. These data suggest SOF+PEG/RBV treatment should still be considered for IFN-eligible GT3 patients, particularly for those with cirrhosis and/or prior treatment failure.