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

Summary 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 ( OP rD) ± 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 OP rD ± 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), OP rD ( N = 297), and OP rD + 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 OP rD and 85.8% (746/869) for OP rD + 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), OP rD 98.0% (248/253) and OP rD + 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/m 2 ( OR 0.73, 95% CI 0.60–0.89, P = 0.002), FIB 4 > 3.25 ( OR 0.60, 95% CI 0.49–0.72, P < 0.001), OP rD + 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 OP rD + RBV likely arose from excess early discontinuation as these factors were no longer significant, when limited to patients completing a 12‐week course.