Efficacy and safety of 6 or 8?weeks of simeprevir, daclatasvir, sofosbuvir for HCV HCV genotype 1 infection

摘要

Summary The phase 2, open‐label ACCORDION (ClinicalTrials.gov: NCT 02349048) study investigated the efficacy, safety and pharmacokinetics of a 6‐ or 8‐week regimen of simeprevir, daclatasvir and sofosbuvir in treatment‐na?ve patients with chronic hepatitis C virus ( HCV ) genotype ( GT ) 1 infection and either early‐stage fibrosis or compensated cirrhosis. Patients were assigned to treatment groups according to their fibrosis stage. Early‐stage fibrosis: simeprevir 150?mg, daclatasvir 60?mg, sofosbuvir 400?mg once daily for 6?weeks; compensated cirrhosis: same regimen for 8?weeks. The primary endpoint was sustained virologic response 12?weeks after the end of treatment ( SVR 12). Safety, tolerability and pharmacokinetics of simeprevir, daclatasvir and sofosbuvir were investigated. Sixty‐eight patients were treated (6‐week group: n?=?59; 8‐week group: n?=?9). SVR 12 was achieved by 86.4% (51/59) of patients with early‐stage fibrosis and by 100% (9/9) of patients with cirrhosis. The main reason for not achieving SVR 12 in the 6‐week group was viral relapse (11.9%; 7/59). One patient had on‐treatment failure due to an early withdrawal (lost to follow‐up due to incarceration). One patient with SVR 12 in the 6‐week group had a late viral relapse at post‐treatment week 24. No clinically significant drug‐drug interactions were observed. Adverse events were reported in 63.2% of patients (43/68) and were mainly grade 1/2. None of these led to treatment discontinuation. The 3 direct‐acting antiviral regimens of simeprevir, daclatasvir and sofosbuvir were safe and well tolerated in treatment‐na?ve, HCV GT 1‐infected patients with early‐stage fibrosis or compensated cirrhosis.