by Bruce Sylvester – Researchers from a Phase III study report no difference in rates of viral clearance between two anemia management strategies for patients with chronic hepatitis C virus (HVC) genotype 1 infection who were treated with boceprevir (Victrelis, Merck) combined with peginterferon alfa-2b (Pegintron, Merck) and ribavirin.
Lead investigator Fred Poordad, M.D., Chief of Hepatology and Liver Transplantation at Cedars-Sinai Medical Center in Los Angeles, California, said that the anemia was managed equally well by reduction of ribavirin or addition of erythropoietin (EPO).
Researchers enrolled 687 treatment-naïve adult subjects with chronic HCV genotype 1, with hemoglobin levels of less than or equal to 15 g/dL.
The subjects were treated with a 4-week lead-in of peginterferon alfa-2b (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of boceprevir (800 mg three times a day) after week 4 for 24 or 44 weeks based on HCV-RNA levels at treatment week 8. They were monitored for development of anemia.
Sixteen (16) percent (111/687) of the subjects were enrolled in cohort 1 and they were assigned a fixed-dose regimen, including the 4-week lead-in of ribiviran, followed by boceprevir for 44 weeks. A protocol amendment was added to the trial that allowed for the use of the response-guided therapy (RGT) paradigm, consistent findings in the pivotal clinical studies for boceprevir. The rest of the subjects patients were enrolled in cohort 2.
Results for subjects in cohort 1 and cohort 2 did not differ, and were combined in the study presentation. Five-hundred subjects developed anemia. They were randomized to receive either ribavirin dose reduction (by 200 to 400 mg/d) or addition of EPO (40,000 IU/week).
A secondary method of anemia management, such as the addition of EPO, ribavirin dose reduction or transfusion, was possible if hemoglobin reached less than or equal to 8.5 g/dL. And treatment was stopped if hemoglobin became less than or equal to 7.5 g/dL.
If the initial hemoglobin measurement qualifying a patient as anemic was less than or equal to 8.5 g/dL, that patient was not randomized to one of the anemia management strategies.
The primary endpoint was the comparison of sustained virologic response (SVR) in patients who were randomized to ribavirin dose reduction or to EPO.
Sustained virologic response rates were 71 percent for subjects treated by ribavirin dose reduction (178/249) and those treated with erythropoietin. (178/251). Rates of relapse were the same, 10 percent in each group. Safety profiles were similar for both strategies.
Dr. Poordad concluded, “There were no meaningful differences in sustained virologic response rates between either of the two anemic management strategies. These data support the use of ribavirin dose reduction as the primary strategy for anemia management.”
Merck & Co. supported the research.