Safety and Efficacy of Ledipasvir plus Sofosbuvir with or without ribavirin in hepatitis C genotype 1 patients who failed previous treatment with Simeprevir plus Sofosbuvir




Modi, Apurva
Gonzales, Gabriel


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Combination therapy with Simeprevir (SIM), NS3/4 protease inhibitor, with Sofosbuvir (SOF), NS5b polymerase inhibitor is an FDA approved treatment option for chronic hepatitis C genotype 1 patients with an over all SVR 12 rate of 85-95%. Single tablet fixed dose combination of Ledipasvir (LDV), NS5a inhibitor, with SOF is also FDA approved for treatment of hepatitis C genotype 1 with SVR 12 rates of ≥ 95%. However, there is no data on the efficacy of retreatment with LDV+SOF in patients who failed initial treatment with SIM+SOF. Methods: Data was collected from treatment cohorts at 2 large hepatology referral centers in Dallas-Fort Worth area. Patients included in the analysis were previously treated with SIM+SOF with or without RBV for 12 weeks but failed to achieve SVR 12 and then undergone re-treatment with LDV+SOF with or without RBV for 12-24 weeks. Patients with cirrhosis, including decompensated Child’s class B or C were included. Decompensation was defined by the presence of fluid overload, hepatic encephalopathy or variceal bleeding. Patients with HCC as the only event that defined decompensation were excluded.. Patients received singlet tablet fixed-dose combination of Ledipasvir 90 mg with Sofosbuvir 400 mg PO +/- wt based ribavirin (RBV) daily for 12-24 weeks at the discretion of the treating hepatologist. Baseline and end of treatment (EOT) laboratory tests & viral load were obtained on all patients. SVR 12 defined as undetectable viral load 12 weeks after EOT was collected on all patients who had reached that time point by Nov 10, 2015. Adverse effects during treatment were obtained on all patients. Data was analyzed using 2 sided t test for continuous variables and chi-quare test for categorical variables. Results: SVR 12 was achieved for 11/13 of all patients and 10/11 for patients who were cirrhotic. 100% (29/29) had achieved EOT response. 10/29 had no side effects on treatments. Of those who had side effects, none were considered severe enough to warrant discontinuation. Conclusions: Ledipasvir + Sofosbuvir is a viable treatment option with high SVR 12 rate in patients who have failed 12 weeks of treatment with SIM + SOF. High SVR 12 rates of 100% (4/4) & 86% (6/7) were achieved in patients with compensated and decompensated cirrhosis respectively •Treatment was generally well tolerated requiring no discontinuations including in those with cirrhosis