Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4–5 chronic kidney disease (the C-SURFER study): a combination phase 3 study

"C-SURFER is a multicentre, phase 3, double-blind study comprising a randomised study of safety and an observational study of efficacy. Adult patients infected with HCV genotype 1 and with chronic kidney disease (stage 4–5 with or without haemodialysis dependence) were selected for inclusion. Complete eligibility criteria are provided in the study protocol. Chronic kidney disease stages 4 and 5 were defined based on eGFR (according to the Modification of Diet in Renal Disease [MDRD]-4 equation)16 15–29 mL/min per 1·73 m2 and less than 15 mL/min per 1·73 m2 or on dialysis, respectively."

"In the full analysis set population, 115 (94%) of 122 patients achieved SVR12. Of the seven patients who did not achieve SVR12, six patients discontinued the study for reasons other than virological failure and one patient relapsed.

High response rates were observed in all subgroups, including haemodialysis and non-haemodialysis, and those with characteristics historically associated with poor response to HCV therapy. In particular, SVR12 was achieved in 51 (100%) of 51 African American patients, 86 (99%) of 87 patients with the IL28B non-CC genotype, 40 (98%) of 41 patients with diabetes, and all six patients with cirrhosis.

No patient discontinued due to an adverse event in the immediate treatment group

Overall, 179 (76%) of 235 patients were on haemodialysis and 191 (81%) had chronic kidney disease stage 5 at baseline. 80 (34%) patients had diabetes, 96 (41%) had cardiovascular disease, 122 (52%) had HCV genotype 1a infection, 189 (80%) were HCV treatment-naive, and 14 (6%) were cirrhotic.

This study shows that the combination of grazoprevir and elbasvir for 12 weeks is an effective treatment regimen for patients with HCV genotype 1 infection and advanced stage 4–5 chronic kidney disease, including patients on haemodialysis and those considered difficult to treat with interferon-based antiviral therapy. Only one (<1%) of 116 patients who completed treatment with grazoprevir and elbasvir did not achieve SVR12. This non-cirrhotic patient with a NS5A L31M mutation at baseline relapsed after having undetectable HCV RNA at the end of treatment and at the 4-week post-treatment visit. No patient had on-treatment virological breakthrough. The short, 12-week duration of treatment with grazoprevir and elbasvir might allow waitlisting of patients for kidney transplant while on treatment for HCV infection, a practice that was previously difficult due to the 24–48 weeks of treatment needed with peginterferon and ribavirin regimens.

In conclusion, the results from the C-SURFER study suggest that a once-daily oral regimen of grazoprevir and elbasvir for 12 weeks has an acceptable safety profile and can achieve high rates of SVR in patients with HCV genotype 1 infection and advanced chronic kidney disease. The results of this study show that the efficacy and safety profile of this combination is consistent across many patient subgroups, including those receiving haemodialysis."