Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir in Patients With Hepatitis C Virus Genotype 1 or 4 Infection and Advanced Kidney Disease

Abstract

Introduction: Hepatitis C virus (HCV) infection is common in patients with end-stage renal disease. We investigated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) ± dasabuvir (DSV) ± ribavirin (RBV) in 2 phase 3, open-label, multicenter studies in patients with stage 4 or 5 chronic kidney disease (CKD).

Methods: RUBY-I, Cohort 2 enrolled treatment-naïve or -experienced patients with HCV genotype (GT) 1a or 1b infection, with or without cirrhosis. Patients received 12 weeks (24 weeks for GT1a patients with cirrhosis) of OBV/PTV/r + DSV; all GT1a patients received RBV. RUBY-II enrolled treatment-naïve patients with GT1a or GT4 infection without cirrhosis. All patients received 12 weeks of RBV-free treatment: OBV/PTV/r + DSV for GT1a-infected patients; OBV/PTV/r for GT4-infected patients. The primary endpoint was sustained virologic response at posttreatment week 12 (SVR12).

Results: RUBY-I, Cohort 2 and RUBY-II enrolled 66 patients, including 50 (76%) on dialysis; 15 (23%) had compensated cirrhosis. Overall, the SVR12 rate was 95% (63/66); 1 patient had virologic failure. There were 3 discontinuations due to adverse events. Seventy-three percent (27/37) of patients receiving RBV had adverse events leading to RBV dose modification. The RBV-free RUBY-II study had no hemoglobin-associated adverse events.

Conclusion: Treatment with OBV/PTV/r ± DSV ± RBV was well tolerated and patients with HCV GT1 or 4 infection and stage 4 or 5 CKD had high SVR12 rates, including patients with compensated cirrhosis and/or prior treatment experience.

Keywords: NS3/4A protease inhibitor; NS5A inhibitor; RUBY; chronic kidney disease; renal disease.

Figure 1

RUBY-I, Cohort 2 and RUBY-II study design. Cohort 2 of RUBY-I included 2 arms, A and B, that enrolled patients with genotype (GT)1a infection and were treated with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) + dasabuvir (DSV) ± ribavirin (RBV). Patients in arm A were noncirrhotic and were treated for 12 weeks. Patients with cirrhosis were enrolled into arm B and were treated for 24 weeks. Patients in arm C of RUBY-I, Cohort 2 had GT1b infection and were treated with OBV/PTV/r + DSV without RBV for 12 weeks. In RUBY-II, all patients were noncirrhotic; those with GT1a were treated with OBV/PTV/r + DSV without RBV for 12 weeks. Patients with GT4 infection were treated with OBV/PTV/r without RBV for 12 weeks. SVR12, sustained virologic response at posttreatment week 12.

Figure 2

Sustained virologic response at posttreatment week 12 (SVR12) rates across the RUBY study series. This graph shows SVR12 rates across all of the RUBY studies, including RUBY-I, Cohort 1. Both RUBY-I, Cohort 2 and RUBY-II included patients with prior hepatitis C virus (HCV) treatment experience; however, in RUBY-II, patients were noncirrhotic and ribavirin (RBV) was not coadministered for patients with any HCV genotype. Overall, in patients with stage 4 or 5 chronic kidney disease, treatment with ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) ± dasabuvir (DSV) regimens resulted in high SVR rates for patients with HCV genotype (GT)1 or 4 infection, including those with concomitant cirrhosis and prior treatment experience. Tx, treatment; w/, with.