Real-world evidence on all-oral, interferon-free regimens with Ombitasvir/Paritaprevir/r and Dasabuvir for treatment of chronic HCV patients with renal insufficiency in the German Hepatitis C-Registry

Background: Chronic hepatitis C virus (HCV) infection is common in patients with renal insufficiency and end-stage renal disease, but clinical data on HCV therapy in this patient group is limited. The direct-acting antiviral regimen of ombitasvir (OBV), paritaprevir (co-dosed with ritonavir, PTV/r) with dasabuvir (DSV) with or without ribavirin (RBV) was approved in 2015 in Germany for treatment of patients with chronic hepatitis C genotype 1 (GT1) and 4 (GT4) infection. However, real-world data on this regimen in patients with renal insufficiency and end-stage renal disease is currently limited.

Goals: In this analysis, we report the real-world effectiveness and safety of OBV/PTV/r ± DSV ± RBV in patients with renal insufficiency in the German Hepatitis C-Registry (DHC-R).

Methods: The DHC-R is a non-interventional, prospective cohort study with more than 300 study sites in Germany. Patients with an eGFR < 90 ml/min/1.73 m2 and chronic HCV GT1 or GT4 infection treated with OBV/PTV/r ± DSV ± RBV between February 1, 2014 and December 7, 2015 were analyzed. Effectiveness was assessed by SVR at post-treatment week 12 or 24 (SVR12/24) and safety is reported in all patients that received at least one dose of study drug.

Results: In total, 326 patients with renal insufficiency received OBV/PTV/r ± DSV ± RBV. 52/326 (16%) patients had moderate (eGFR 30 – 60 ml/min/1.73 m2; n = 36) to severe (eGFR < 30 ml/min/1.73 m2; n = 16) renal insufficiency (incl. 8 patients on hemodialysis). 85/326 (26%) had cirrhosis and 202/326 (62%) were treatment-experienced. 61 (19%), 229 (70%), 7 (2%) and 29 (9%) were infected with HCV GT1a, GT1b, an unspecified GT1-subtype or GT4, respectively. Of 193 patients who reached post-treatment follow-up, 96% (152/159) of patients with mild renal insufficiency and all patients (100%; 34/34) with moderate to severe renal insufficiency achieved SVR12/24. Adverse events (AE) were reported in 188/326 (58%) of patients, specifically in 109/160 (68%) who received RBV and in 79/166 (48%) who did not. The rate of treatment discontinuations due to AE was 6.3% (10/160) in patients treated with RBV and 0.6% (1/166) in patients treated without RBV. Clinically significant changes in renal function were not observed when comparing eGFR at baseline and end of treatment in the overall population (Δ eGFR: – 2.1 (mean)± 10.8 (SD) ml/min/1.73 m2) or in different subgroups, incl. patients with severe renal insufficiency.

Conclusions: In this real-world cohort of HCV GT1- and GT4-infected patients, treatment of patients with renal insufficiency with OBV/PTV/r ± DSV ± RBV was well tolerated and achieved high rates of SVR, irrespective of baseline renal function.