Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection.

BACKGROUND & AIMS: We performed a phase 2 clinical trial to evaluate the efficacy and safety of ledipasvir and sofosbuvir, with or without ribavirin, in patients infected with hepatitis C virus (HCV) genotype 3 or 6. METHODS: We performed an open-label study of 126 patients with HCV genotype 3 or 6 infections at 2 centers in New Zealand from April 2013 through October 2014. Subjects were assigned 1 of 4 groups that received 12 weeks of treatment. Previously untreated patients with HCV genotype 3 were randomly assigned to groups given fixed-dose combination tablet of ledipasvir and sofosbuvir (n = 25) or ledipasvir and sofosbuvir along with ribavirin (n = 26). Treatment-experienced patients with HCV genotype 3 (n = 50) received ledipasvir and sofosbuvir and ribavirin. Treatment-naïve or treatment-experienced patients with HCV genotype 6 (n = 25) received ledipasvir and sofosbuvir. The primary end point was the percentage of patients with HCV RNA ≤15 IU/mL 12 weeks after stopping therapy (sustained virologic response at 12 weeks [SVR12]). RESULTS: Among treatment-naïve genotype 3 patients, 16 of 25 (64%) receiving ledipasvir and sofosbuvir alone achieved SVR12 compared with all 26 patients (100%) receiving ledipasvir and sofosbuvir and ribavirin. Among treatment-experienced patients with HCV genotype 3, forty-one of fifty achieved an SVR12 (82%). Among patients with HCV genotype 6, the rate of SVR12 was 96% (24 of 25 patients). The most common adverse events were headache, upper respiratory infection, and fatigue. One patient with HCV genotype 3 discontinued ledipasvir and sofosbuvir because of an adverse event (diverticular perforation), which was not considered treatment related. CONCLUSIONS: In an uncontrolled, open-label trial, high rates of SVR12 were achieved by patients with HCV genotype 3 infection who received 12 weeks of ledipasvir and sofosbuvir plus ribavirin, and by patients with HCV genotype 6 infection who received 12 weeks of sofosbuvir and ledipasvir without ribavirin. Current guidelines do not recommend the use of ledipasvir and sofosbuvir, with or without ribavirin, in patients with HCV genotype 3 infection. ClinicalTrials.gov Number: NCT01826981.

Interferon alpha (pegylated and non-pegylated) and ribavirin for the treatment of mild chronic hepatitis C: a systematic review and economic evaluation.

OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of pegylated interferon alpha (PEG) and non-pegylated interferon alpha (IFN) and ribavirin (RBV) for the treatment of adults with histologically mild chronic hepatitis C (HCV) infection. DATA SOURCES: Electronic bibliographic databases were searched up to July 2005. REVIEW METHODS: A systematic review and an economic evaluation were carried out. A Markov state transition model was developed to estimate the cost-effectiveness of treatment strategies for adults with mild chronic HCV. RESULTS: Among the included studies, eight randomised controlled trials (RCTs) of antiviral treatment in mild HCV were identified and included. In general these RCTs were of good quality. The results suggested that effectiveness, particularly with respect to sustained virological response was similar in patients with mild disease to the results obtained in patients with moderate/severe disease. This finding was supported by RCTs reporting the results for mild HCV sub-groups. The authors' cost-effectiveness analysis showed that early treatment compared with watchful waiting is associated with quality-adjusted life-year (QALY) gains but with increased treatment costs. The base-case incremental costs per QALY for 48 weeks of treatment are: watchful waiting with IFN + RBV versus best supportive care = pound 3097-6585; early treatment with IFN + RBV versus watchful waiting with IFN + RBV = pound 5043-8092; watchful waiting with PEG 2a + RBV versus best supportive care = pound 3052; early treatment with PEG 2a + RBV versus watchful waiting with PEG 2a + RBV = pound 5900; watchful waiting with PEG 2b + RBV versus best supportive care = pound 2534; and early treatment with PEG 2b + RBV versus watchful waiting with PEG 2b + RBV = pound 5774. These results were consistent with previous assessments of cost-effectiveness. CONCLUSION: This systematic review and economic evaluation show that patients with histologically mild HCV can be successfully treated with both pegylated and non-pegylated interferon alpha. Early treatment and watchful waiting strategies are associated with acceptable cost-per-QALY estimates. Research needs to be directed towards newer, potentially more effective interventions, particularly those that improve treatment response in patients with genotype 1, with minimal adverse effects. Further research is required into the natural history of HCV to estimate better the rate of liver disease progression, and also into the effectiveness of non-invasive biochemical markers of liver disease, as an alternative to liver biopsy.