Pegylated Interferon Alfa 2b (PEG-IFN) and Ribavirin for Hepatitis C Patients who Were Nonresponders to Previous Therapy

Eric J. Lawitz, Norma S. Cantu, Scott Becker, Ravi Dhar, Jianjun Li, Natrajan S. Bala, Stuart Gordon, Mitchell Davis, Pierre Nader, Kent Holtzmuller, Thomas Rosenfield, Howard Monsour, Alamo Study Group, San Antonio, TX; Austin, TX; Detroit, MI; Jacksonville, FL; Houston, TX; Royal Oak, MI; West Palm Beach, FL; Seattle, WA; Washington, DC; Altantis, FL

There are currently no accepted treatment options for standard combination therapy nonresponders. Viral kinetics studies have shown an early dose dependent phase of viral clearance. The induction strategy was introduced based on this data but trials have not shown a benefit to this strategy, however these trials have not followed induction with continuous interferon for the entire 48 weeks. PEG-IFN allows a convenient mechanism to deliver continuous interferon, possibly making the induction strategy more successful.

The aim of this study is to evaluate the efficacy of induction PEG-IFN and ribavirin compared to fixed dose PEG-IFN and ribavirin in previous standard combination therapy nonresponders, IFN monotherapy nonresponders, and combination therapy relapsers. Methods: Participants were randomized to receive either PEG-IFN 1.5 mcg/kg/wk + Ribavirin 1000-1200mg daily x 12 weeks then PEG-IFN 1.0mcg/kg/wk + Ribavirin 800mg x 36 weeks or PEG-IFN 1.0 mcg/kg/wk + Ribavirin 800 mg for 48 weeks. HCV-RNA was measured at week 0, 24, & 48 of treatment and 24 weeks post treatment. Results: Five hundred and one previous combination therapy nonresponders, 122 IFN monotherapy nonresponders, and 130 combination therapy relapsers with compensated liver disease were enrolled. Baseline characteristics include: Genotype 1-84%, African Americans-17%, and advanced liver disease-43%. Two-hundred and sixty five combination therapy nonresponders (Combo NR), 64 interferon monotherapy nonresponders (Mono NR) and 56 combination therapy relapsers (Combo Relapser) have completed 24 weeks of therapy. Results for 24 week and partial 48 weeks are seen in the table below. The authors additionally looked at a subset of patients defined as partial responders. Partial responders were patients that during previous therapy had = or > that a 1 log drop in HCV RNA during previous therapy. These patients had an EOT response of 46% compared to 20% in patients that had not achieved that defined previous partial response. Discontinuations in this study were approximately 22-23%. PEG-IFN was reduced in 7% while ribavirin was reduced 5-6%.

In summary, even though SVR’s are not yet available interim results suggest the use of induction dosing does not significantly improve the twenty-four week or EOT viral clearance rates in the three groups evaluated, with the presenter stating no statistical significance in the EOT result between induction and fixed dosing in the combination relapser.