Real World Effectiveness of Ledipasvir/Sofosbuvir in 4365 Treatment-Naïve Genotype 1 Hepatitis C Infected Patients

Abstract

Real-world effectiveness data is needed to inform hepatitis C virus (HCV) treatment decisions. The uptake of ledipasvir/sofosbuvir (LDV/SOF) regimens across healthcare settings has been rapid but variations often occur in clinical practice. The aim of this study was to assess sustained virologic response (SVR) of LDV/SOF±ribavirin (RBV) in routine medical practice. This observational, intent-to-treat cohort was comprised of 4365 genotype 1 treatment-naïve HCV-infected veterans treated with LDV/SOF±RBV. SVR rates were 91.3% (3191/3495) for LDV/SOF and 92.0% (527/573) for LDV/SOF+RBV (p=0.65). African American race (OR 0.70, 95%CI 0.54-0.90, p0.004) and FIB-4 >3.25 (OR 0.56, 95%CI 0.43-0.71, p<0.001) were independently associated with decreased likelihood of SVR; age, sex, BMI, decompensated liver disease, diabetes, genotype 1 subtype and regimen did not predict SVR. In models limited to those who completed 12 weeks of treatment, African American race was no longer a significant predictor of SVR but FIB-4 >3.25 (OR 0.35, 95%CI 0.24-0.50, p<0.001) remained. Among non-cirrhotics (defined by FIB-4≤3.25) with baseline HCV RNA<6,000,000 IU/ml, SVR rates were 93.2% (1020/1094) for those who completed 8 weeks of therapy and 96.6% (875/906) for those who completed 12 weeks of therapy (p=0.001). Conclusions: In this real-world cohort, SVR rates with LDV/SOF±RBV nearly matched the rates reported in clinical trials and were consistently high across all subgroups. Non-cirrhotics with HCV RNA<6,000,000 IU/mL were less likely to achieve SVR with 8 weeks compared to 12 weeks of therapy although the numeric difference in SVR rates was small.