A Single U. S. Center Experience with Daily High Dose Consensus Interferon and Ribavirin in Hepatitis C Patients Who are Resistant to PEG-Interferon and Ribavirin

Abstract

Purpose: The majority of nonresponder and relapser patients with chronic hepatitis C are unable to achieve a sustained virologic response (SVR) with the combination of PEG-Interferon (PEG-IFN) and ribavirin (RBV), especially those who have genotype 1 and advanced disease. Consensus interferon (Interferon alfacon-1, CIFN) is a bio-optimized alfa interferon that exhibits increased in-vitro antiviral activity than the naturally occurring alfa interferons 2a and 2b. Improved response rates have been reported with high-dose CIFN therapy and RBV for patients who have failed to respond to PEG-IFN/RBV. This study will evaluate the efficacy and safety of high-dose daily CIFN and RBV in HCV patients who failed therapy with PEG-IFN/RBV. Methods: Patients who had been treated with PEG-IFN/RBV for HCV but did not obtain a SVR were eligible for treatment if they tolerated their previous treatment with PEG-IFN/RBV. Patients were given 27 ug of CIFN daily and RBV 400 mg BID during the first four weeks, followed by 18 ug daily and ribavirin 400 mg BID daily for the next eight weeks. At 12 weeks, CIFN was decreased to 15 ug daily while RBV was increased to 1,000–1,200 mg daily for 36 weeks. Results: Fifty patients were enrolled in the study, 72% male with a mean age of 50 years old. 96% had genotype 1. 22% of patients had stage 2 fibrosis. 60% had stage 3–4 fibrosis, of which 44% of patients had cirrhosis. 76% of patients were nonresponders. 38 patients (76%) achieved an early virologic response (EVR) while 25 patients (50%) were undetectable at 12 weeks. 16 patients (52%) were undetectable at 24 weeks and 20 patients (40%) achieved an End-of-Treatment response (EOT). In an Intention to treat analysis (ITT) of the 50 patients who have completed 72 weeks of treatment, 20 patients achieved an EOT (40%) while 6 of these patients (12%) have achieved a Sustained Virological Response (SVR). Therefore, the relapse rate was 70%. Growth factors were used in over 40% of patients with corresponding dose reductions in 20%. Conclusion: For HCV patients with advanced histologic disease who had previously failed therapy with PEG-IFN and RBV, the combination of high-dose CIFN and RBV is a well-tolerated and effective option. 12% of patients achieved a SVR. This SVR rate was limited by an extremely high rate of relapse. This relapse rate was similar to that seen in the DIRECT trial. It confirms the need for nonresponder studies with both higher doses of RBV and longer duration of treatment with CIFN in order to reduce the rate of relapse.Table