PEG-interferon alfa-2b plus ribavirin for treatment of CHC patients who failed or relapsed following interferon-based therapy

The role of PEG-Intron (pegylated interferon alfa-2b/ PEG) and ribavirin (RBV) therapy for patients with chronic hepatitis C (HCV) who have previously failed interferon (IFN)-based therapies is not fully known.

The objective of the current study was to compare the safety and efficacy of continuous weight-based (CONT) versus. categorical weight-based (CAT) PEG-IFN alfa-2b/RBV in patients who have failed to achieve sustained virologic response after previous IFN/RBV treatment.

This is an open-label, multi-centre, randomised clinical trial of CONT vs. CAT PEG/RBV. Patients were randomised to receive 800mg RBV QD with either continuous weight adjusted PEG-IFN aldfa-2b (1.5 mcg/kg) QW (n=259) or categorical weight adjusted PEG-IFN alfa-2b (100 mcg if < 80kg, 150 mcg if > 80kg) for 48 weeks. HCV RNA was evaluated at baseline (BL), week 12 (EVR), and end of treatment (EOT). Intent-to-treat response rates were compared using Fischer’s Exact Test and logistic regression.

517 patients were enrolled and took at least one dose of drug. The median age was 47 years, and the patients were 64.8% male, 76.8% Caucasian, 13.5% Black and 8.3% Asian. HCV Genotype 1, 90.5% and 2 or 3, 9.5%.

Two hundred and seven patients completed 48 weeks of treatment. Two hundred and seventy-eight patients withdrew before EOT; the primary reason for withdrawal was viral non-response.

No differences were observed in AEs between treatment groups, including neutropenia (p=0.7). EVR/EOT for CONT and CAT were 40.0%/24.3% and 31.0%/25.6%, respectively (p=0.47 and 0.64)). EVR/EOT for relapsers and non-responders were 50.6%/34.9% and 23.9%/20.3%, respectively (p < .0003). EOT response was 23.8% in genotype 1 and 36.7% in genotype 2/3(p=0.046).

Conclusions: continuous and categorical weight-based dosing of PEG-IFN alfa-2b/RBV had similar safety and efficacy in the re-treatment of patients who failed or relapsed after original IFN-based therapy for HCV.

Among non-responders to prior therapy, the EOT response was more than 20%; as expected the EOT was higher among relapsers.

These data suggest that PEG-IFN alfa-2b/RBV may be effective in persons who initially failed to respond to or relapsed after previous IFN/RBV treatment.

M Sulkowski et al. PEG-interferon alfa-2b + ribavirin for treatment of patients with chronic hepatitis C who have previously failed to achieve a sustained virologic response following interferon alfa or interferon a-2b + ribavirin therapy. Abstract T1292 (poster). Abstracts of Digestive Disease Week 2003. May 17-22, 2003. Orlando, FL.

Comment

Although sustained responses are awaited, these early data suggest that in previous Interferon +/- ribavirin non-responders, up to 20% may achieve end of therapy responses. Although this may not translate into sustained response, as shown by the study below, these patients will gain benefit in terms of HAI score improvement.

Perhaps of slight concern from this study is the end of therapy responses in relapsers. This study suggests that only 50% of those who had all, by definition, had end of therapy response to previous interferon +/- ribavirin will achieve the same with re-treatment with PEG-IFN and ribavirin.

This suggests that for half of these patients, previous non-sustained response may in some way have rendered them unresponsive to further interferon-based treatment.

While we await the final data, further analysis of the viral genomic characteristics of these patients will be of interest in determining whether interferon therapy selects for, or induces viral resistance.