Comparative effectiveness of ledipasvir/sofosbuvir±ribavirin vs. ombitasvir/paritaprevir/ritonavir plus dasabuvir±ribavirin in 6961 genotype 1 patients treated in routine medical practice

BackgroundReal-world data are needed to inform hepatitis C virus (HCV) treatment decisions. AimTo assess the comparative effectiveness of ledipasvir/sofosbuvirribavirin (LDV/SOFRBV) vs. ombitasvir/paritaprevir/ritonavir+dasabuvir (OPrD)RBV in genotype 1 HCV patients treated in routine medical practice. MethodsObservational intent-to-treat cohort of genotype 1 patients initiating 8 or 12weeks of LDV/SOF +/- RBV or 12weeks of OPrD +/- RBV. Sustained virological response (SVR) required RNA below the limit of quantification at least 10weeks after end of treatment. Results6961 patients initiated LDV/SOF (N=4478), LDV/SOF+RBV (N=1269), OPrD (N=297), and OPrD+RBV (N=917) at 126 facilities. Intention-to-treat SVR rates were 91.4% (3813/4170) for LDV/SOF, 90.0% (1098/1220) for LDV/SOF+RBV, 95.1% (269/283) for OPrD and 85.8% (746/869) for OPrD+RBV. SVR rates in those completing 8weeks of LDV/SOF were 91.7% (1223/1333) and 12weeks of LDV/SOF 94.6% (2475/2615), LDV/SOF+RBV 92.2% (1033/1120), OPrD 98.0% (248/253) and OPrD+RBV 95.5% (705/738). Significant predictors of SVR were African American race (OR 0.71, 95%CI 0.59-0.86, P<0.001), body mass index (BMI)>30kg/m(2) (OR 0.73, 95% CI 0.60-0.89, P=0.002), FIB4>3.25 (OR 0.60, 95% CI 0.49-0.72, P<0.001), OPrD+RBV compared to LDV/SOF (OR 0.60, 95% CI 0.48-0.76, P<0.001) and subtype 1b (OR 1.38, 95% CI 1.11-1.71, P=0.003). For those completing 12weeks, FIB-4>3.25 and high BMI remained significant predictors. ConclusionsIn this robust real-world cohort, SVR rates were similar to clinical trials. FIB-4>3.25 and high BMI were significant negative predictors of SVR. Reduced odds of SVR in African Americans and with OPrD+RBV likely arose from excess early discontinuation as these factors were no longer significant, when limited to patients completing a 12-week course.