The EPIC 3 trial, sponsored by Schering-Plough, included a prospective analysis to evaluate the safety and efficacy of retreatment of non-responders with pegylated interferon alfa-2b (PegIntron) plus ribavirin.

Results were presented at a late-breaker session at the 43rd annual meeting of the European Association for the Study of the Liver (EASL) last week in Milan.

The primary objective of the study was to determine sustained virological response (SVR) rates among 820 patients who had previously been treated with PegIntron or pegylated interferon alfa-2a (Roche's Pegasys) and 1203 who had previously received conventional interferon alfa, all with ribavirin.

The analysis included both compete non-responders and patients who relapsed after previous interferon/ribavirin treatment and had Metavir fibrosis scores of F2-F4. Most were men (71%) and white (84%), with a mean age of 49 years. About a third (37%) had baseline HCV RNA of 600,000 IU/mL or higher and 80% had HCV genotype 1.

For retreatment, all received 1.5 mcg/kg/week PegIntron plus the Rebetol brand of ribavirin at 800-1400 mg/day, depending on weight, for up to 48 weeks.

Plasma HCV RNA was assessed at treatment weeks 12, 24, and 48, and at follow-up weeks 12 and 24 using the quantitative Taq-Man assay (SPRI; sensitivity 125 IU/mL).

Results

• Overall, in the full cohort, the SVR rate was 22%.

• The likelihood of achieving SVR was greatly influenced by participants' baseline characteristics.

• Generally, prior relapsers responded better than complete non-responders (38% vs 14%).

• However, HCV genotype, degree of fibrosis, and type of prior treatment were also important factors predictive of SVR;

• Genotype 2/3 subjects responded better than those with genotype 1 regardless of prior response (see table below).

• Undetectable HCV RNA at treatment week 12 remained the most important predictor of SVR.

• 56% of subjects with undetectable HCV RNA at week 12 achieved SVR vs 5% with a 2-log or greater decrease in, yet still detectable, viral load.

• Among subjects with undetectable HCV RNA at treatment week, the only significant predictors of SVR were genotype and fibrosis stage.

Conclusion

These findings led the study authors to conclude that HCV genotype is the most predictive factor for SVR after retreatment of patients who failed previous treatment with interferon/ribavirin.

In addition, the authors noted that genotype 2 and 3 patients responded better than those with genotype 1, independent of prior treatment received and prior response. Finally, they concluded that fibrosis is also an important predictor of response across all genotypes.

5/02/08

Reference
T Poynard, M Colombo, J Bruix, and others (EPIC3 Study). Sustained Viral Response Is Dependent on Baseline Characteristics in the Re-treatment of Previous Interferon/Ribavirin Non-responders: Final Results from the EPIC 3 Program. 43rd Annual Meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.