By Liz Highleyman

Only about half of all people with chronic hepatitis C virus (HCV) infection achieve a "cure" or sustained virological response (SVR) after completing current standard treatment with pegylated interferon plus ribavirin. Researchers have therefore explored various therapies in the hopes of slowing, halting, or even reversing liver disease progression in patients who do not clear the virus.

At the 43rd annual meeting of the European Association for the Study of the Liver (EASL) this week in Milan, researchers presented the latest results from the COPILOT trial comparing therapies intended to alleviate liver-related complications in patients with advanced liver disease.

In this study, 555 patients who did not respond to interferon-based therapy were randomly assigned (1:1) to receive low-dose (0.5 mcg/kg/week) pegylated interferon alfa-2b (PegIntron) or 0.6 mg twice-daily colchicine for 4 years. Colchicine is an anti-inflammatory agent that has been shown to inhibit mitosis (cell division) and fibrogenesis (production of fibrous tissue).

Participants in both study arms had similar demographic characteristics; 70% were men, 87% were Caucasian, and the mean age was 51 years. At baseline, they had Ishak stage F3-F6 fibrosis; 78% had cirrhosis and 45% had portal hypertension.

Follow-up continued for 4 years; participants were assessed every 3 months and screened for HCC every 6 months. Primary study endpoints were end-stage liver failure, death, liver transplantation, variceal bleeding, and development of hepatocellular carcinoma (HCC). Both intent-to-treat (ITT) analysis and per protocol (PP) analysis with patients censored at time of dropout were performed.

Results

• 110 patients (20%) overall reached one of the clinical endpoints:

• By ITT analysis: 53 in the pegylated interferon arm and 57 in the colchicine arm;

• By PP analysis: 36 in the pegylated interferon arm and 45 in the colchicine arm.

• HCC was more common in the pegylated interferon arm compared with the colchicine arm (26 vs 12 cases).

• Conversely, complications of portal hypertension were more common in the colchicine compared with the pegylated interferon arm (39 vs 26 cases), with the major difference being variceal bleeding.

• Pegylated interferon demonstrated a benefit with regard to event-free survival only in patients with portal hypertension at 2 and 4 years in both ITT and PP analyses.

• Overall, half the participants discontinued therapy during the 4 years of follow-up due to lack of adherence (36%) or side effects (13%).

Conclusion

Based on these findings, the investigators concluded, "Maintenance therapy with [pegylated interferon] was associated with improved disease-free survival almost exclusively in patients with portal hypertension and should be considered in those patients."

Beth Israel Deaconess Medical Center, Boston, MA; Syracuse University, Syracuse, NY; Columbia College of Physicians and surgeons, New York, NY; Liver-Pancreas Institute, Kansas City, MO; Boston University, Boston, MA; Schering Plough, Kennilworth, NJ.

4/25/08

Reference
NH Afdhal, R Levine, R Brown, and others. Colchicine versus Peg-Interferon Alfa 2b Long Term Therapy: Results of the 4 Year COPILOT Trial. 43rd annual meeting of the European Association for the Study of the Liver (EASL 2008). Milan, Italy. April 23-27, 2008.