High Dose Consensus Interferon Induction Therapy Results in Successful Retreatment of Peginterferon Nonresponder HCV Patients

Treatment with pegylated interferon alfa (PEG IFN) and ribavirin (RBV) has an efficacy in chronic hepatitis C patients with sustained response rates of about 50%. However, response in genotype 1 patients with high viral load is considerably lower, with SR rates of 29-34%.

Furthermore, studies of peginterferons have shown low response rates of only 6-12% in the treatment of combination therapy nonresponders.

In contrast, other trials have suggested improved response rates using consensus interferon (interferon alfacon-1, CIFN) in genotype 1 / high viral load patients as well as previous combination therapy non-responders.

In this study, the efficacy of CIFN induction therapy followed by CIFN / RBV combination treatment in PEG IFN combination therapy non-responders was evaluated.

50 patients have been included. All patients had elevated ALT-values and were viremic, with 46 having genotype 1, the remaining genotype 4.

Histologic confirmation of inflammation and fibrosis was obtained in all patients with grading and staging according to Ishak, where 13 patients showed bridging fibrosis or cirrhosis.

Patients were either treated with CIFN at a dosage of 9 ug QD for 16 weeks or with CIFN 27 ug QD for 4 weeks, followed by 12 weeks of CIFN 18 ug QD.

Thereafter, treatment was continued in all groups with CIFN 9 ug QD with RBV (at 10-15 mg/kg/d) for another 34-56 weeks, depending when the PCR result became negative ensuring a negative PCR result for at least 48 weeks under therapy.

Results show that after the initial 24 weeks of CIFN / RBV therapy, a negative PCR was observed in 46% in the CIFN 9 ug / RBV group (n=25), and in 52% of the CIFN 27/18 ug / RBV group (n=25).

End-of-treatment rates were 42% and 48%, respectively.

For the patients already in follow-up the sustained viral response rates were 24% (n=18) and 30% (n=21).

Due to side effects CIFN had to be reduced in 4 patients and discontinued in 2 patients.

The authors conclude, “CIFN daily dosing/induction therapy together with subsequent RBV combination therapy thus shows sustained viral response rates in about one quarter of previous peginterferon combination therapy non-responders.”

“If these response rates can be reproduced in a larger multicenter trial being conducted at present, an effective treatment will be in place for this difficult-to-treat patient group.”

05/17/04

Reference
S Kaiser. [powerpoint] Successful Retreatment of Peginterferon Nonresponder Patients with Chronic Hepatitis C with High Dose Consensus Interferon Induction Therapy. Abstract 125 (oral). Digestive Disease Week 2004. May 15-20. New Orleans, LA.