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

Abstract

Background: Real-world data are needed to inform hepatitis C virus (HCV) treatment decisions. Aim: To assess the comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) vs. ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ± RBV in genotype 1 HCV patients treated in routine medical practice. Methods: Observational intent-to-treat cohort of genotype 1 patients initiating 8 or 12 weeks of LDV/SOF ± RBV or 12 weeks of OPrD ± RBV. Sustained virological response (SVR) required RNA below the limit of quantification at least 10 weeks after end of treatment. Results: 6961 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 8 weeks of LDV/SOF were 91.7% (1223/1333) and 12 weeks 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) > 30 kg/m2 (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 12 weeks, FIB-4 > 3.25 and high BMI remained significant predictors. Conclusions: In 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.