AASLD 2014 - Abstract LB-6 - Ledipasvir/Sofosbuvir Fixed Dose Combination is Safe and Efficaclous In Cirrhotic Patients Who Have Previously Failed Protease-inhibitor Based Triple Therapy
M. Bourliere, et al.
Background: HCV-infected patients with cirrhosis are a population in urgent need of new treatment options. Suboptimal safety and efficacy have been observed in subjects with cirrhosis who have been treated with a protease inhibitor (PI) + PegIFN+RBV regimen. Here we have assessed the safety and efficacy of ledipasvir/sofobuvir (LDV/SOF) in cirrhotic patients who did not achieve SVR, and previous failed both PegIFN+RBV and subsequently PI+PegIFN+RBV treatment.
Conclusion: LDV/SOF+RBV for 12 weeks and LDV/SOF for 24 weeks resulted in similarily high SVR rates and were well tolerated in genotype 1 patients with compensated cirrhosis who had failed both PegIFN+RBV and PI+PegIFN+RBV. These patients are at high risk for disease progression and have previously had limited treatment options.
CARE Faculty Canadian Perspective:
Interferon-based antiviral therapy is poorly tolerated and has sub-optimal efficacy in many patients with cirrhosis. For example, in the CUPIC study from France (Hezode et al. Gastro 2014), cirrhotic, genotype 1 (G1)-infected patients treated with triple therapy including boceprevir or telaprevir had SVR rates of only ~40%. Approximately one-half of these patients had serious adverse events including hepatic decompensation (5%), severe infection (7%), and death (2%). In the SIRIUS study described above, Bourliere and colleagues examined the safety and efficacy of the sofosbuvir/ledipasvir (SOF/LDV) single tablet regimen (STR) in patients with compensated cirrhosis due to HCV, including 30% who were in the CUPIC study. Patients were randomized to receive the Health Canada and U.S. FDA-approved regimen of SOF/LDV for 24 weeks or a truncated 12-week regimen that also included weight-based ribavirin (RBV). SVR12 rates were 97% and 96%, respectively, demonstrating that 12 weeks of SOF/LDV plus RBV is sufficient for re-treatment of cirrhotic patients who have failed prior therapy including protease inhibitors. Importantly, tolerability was excellent (only 1 patient had a treatment-related serious adverse event) and significant improvements in liver function (i.e. albumin and bilirubin) were observed. Based on these findings and the cost-savings of a shortened treatment course, this 12-week regimen of the SOF/LDV STR plus RBV is the preferred option for treatment-experienced patients with G1 and cirrhosis.