Daclatasvir plus sofosbuvir, with or without ribavirin, for hepatitis C virus genotype 3 in a French early access programme

摘要

Abstract Background & Aims Optimally effective treatment for hepatitis C virus genotype 3?(GT3) is urgently needed, particularly in advanced liver disease. Daclatasvir plus sofosbuvir was efficacious in phase 3 studies. Real‐world data for daclatasvir+sofosbuvir in advanced GT 3 infection are presented from the French Temporary Authorisation for Use programme, which allowed patients in need without other treatment options access to daclatasvir ahead of its market authorization. Methods Patients with F3/F4 fibrosis and/or extrahepatic hepatitis C virus manifestations, post‐liver transplant hepatitis C virus recurrence and/or indication for liver/kidney transplant, were treated with daclatasvir+sofosbuvir (60+400?mg daily) for a recommended duration of 24?weeks. Addition of ribavirin and/or shorter treatment was at physician's discretion. The primary efficacy analysis was sustained virological response at post‐treatment week 12 ( SVR 12; modified intention‐to‐treat). Safety was assessed by spontaneous adverse event reporting. Results The efficacy population comprised 333 patients, mostly cirrhotic (77%, of whom 18% were decompensated) and treatment experienced (72%). After 24?weeks of daclatasvir+sofosbuvir, SVR12 was 89% (174/196) overall (95% CI 83.6‐92.5%), 98% (43/44) without cirrhosis (95% CI 88.2‐99.6%) and 86% (129/150) with any degree of cirrhosis (95% CI 79.5‐90.7%), without SVR 12 increase in those who received additional ribavirin for 24?weeks ( SVR 12 82% [50/61; 95% CI 70.5‐89.6%]). Among 516 GT 3‐infected patients with safety data, 5 discontinued for adverse events and 11 died. Conclusions Daclatasvir+sofosbuvir achieved high SVR 12 rates and was well tolerated in this large real‐world cohort of GT 3‐infected patients with advanced liver disease, without benefit of ribavirin in those treated 24?weeks.