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

Abstract

IntroductionHepatitis 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).MethodsRUBY-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).ResultsRUBY-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.ConclusionTreatment 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.

Safety and efficacy of direct-acting antivirals for chronic hepatitis C in patients with chronic kidney disease

“…Concerning the combination paritaprevir/ombitasvir/ ritonavir and dasabuvir, studies have shown good tolerance and efficacy in HCV-infected patients with stage 4/ 5 CKD, including subjects with compensated cirrhosis, previously treated patients and patients undergoing dialysis [10]. We evaluated the safety and efficacy of this therapeutic regimen in a group of 232 patients, including subjects with severe renal impairment, hemodialyzed patients and kidney transplant recipients, all infected with HCV genotype 1.…”

Safety and Efficacy of Paritaprevir/Ritonavir, Ombitasvir, and Dasabuvir for Hepatitis C Virus Infection Across All Levels of Kidney Function

“…This issue of Kidney International Reports features the results of 2 important studies using DAAs in patients with kidney disease 4, 5. In both studies, the DAA regimen evaluated is paritaprevir with the pharmaco-enhancer ritonavir, ombitasvir, and dasabuvir (PROD), a combination DAA therapy that includes 1 drug from each of the major DAA classes (protease inhibitors, polymerase inhibitors, and NS5A protein inhibitors).…”

“… 5 Ribavirin (Yes/No)Cure Rate, %Anemia, %aRenal AEs, %All SAEs, %eGFR ≥90 ( n = 1221)Yes964913eGFR 60–89 ( n = 1254)Yes966123eGFR <60 ( n = 59)Yes9378710eGFR ≥90 ( n = 453)No97211eGFR 60–89 ( n = 547)No98221eGFR <60 ( n = 33)No97236 Advanced CKD: Lawitz et al. 4 %Dialysis DAA regimen Duration, wk Cure rate, % Anemia Ruby-I cohortGT1A without cirrhosis ( n = 28)68PROD + ribavirin1296Grade 2–3 in 71%GT1A with cirrhosis ( n = 9)89PROD + ribavirin2489Grade 2–3 in 75%GT1B with or without cirrhosis ( n = 11)73PROD12100Grade 2 in 27%, no grade 3Ruby-II cohortGT1A without cirrhosis ( n = 13)100PROD12100Grade 2 in 31%, no grade 3GT4 without cirrhosis ( n = 5)80PRO1280Grade 2 in 40%, no grade 3AE, adverse event; CKD, chronic kidney disease; DAA, direct-acting antiviral; GT, genotype; PRO, paritaprevir, ritonavir, ombitasvir; PROD, paritaprevir, ritonavir, ombitasvir, and dasabuvir; SAE, serious adverse event.aAnemia defined as hemoglobin decrease to <10 g/dl or ≥2 g/dl from baseline to end of treatment. Unable to determine from text the breakdown of anemia by CKD stage in those treated with regimens that did not include ribavirin; text notes only 2% had comparable hemoglobin reductions.…”

“…Lawitz and colleagues 4 determined the safety and efficacy of PROD in patients with advanced CKD (eGFR <30 ml/min per 1.73 m 2 ), reporting the combined results of 2 small phase 3, open-label clinical trials: Ruby-I, Cohort 2 (NCT02207088) and Ruby-II (NCT 02487199). A total of 66 patients were included, most (76%) were on dialysis.…”

Facilitating Patient-Centered Decision Making Around the Timing of Direct-Acting Antivirals in Patients With Hepatitis C Virus and CKD

“…9 Post hoc analyses of trial data and observational evidence suggest that virologic cure of HCV infection with DAAs improves kidney outcomes (ie, proteinuria and estimated glomerular filtration rate) in many patients with CKD. 12 , 13 , 14 Further investigation with longer follow-up is needed to better understand the effect of DAA treatment on long-term kidney outcomes in patients with CKD, and to evaluate whether treatment reduces adverse outcomes in dialysis patients. 15 In individuals with HCV infection on the kidney transplant waitlist, willingness to accept an HCV-positive donor kidney can greatly reduce the time they wait to receive a kidney transplant.…”