Sustained Virological Response to Pegylated Interferon Alfa-2b (PegIntron) with or without Ribavirin Predicts Continued Response through 5 Years

Sustained virological response (SVR), or continued undetectable HCV viral load 24 weeks after completion of interferon-based therapy, is widely regarded as a cure for chronic hepatitis C.

As reported at the recent Digestive Disease Week 2008 conference in San Diego, Karen Lindsay and an international team of colleagues conducted a study to confirm whether SVR predicts long-term (> 5 years) HCV clearance in adults treated with pegylated interferon, as has already been demonstrated for conventional interferon.

The present analysis included 567 adult chronic hepatitis C patients from 2 previously published clinical trials (Lindsay et al, Hepatology 2001, 34:395-403; Manns et al, Lancet 2001, 358:958-965) who were treated with pegylated interferon alfa-2b (PegIntron) with or without ribavirin.

Participants completed the initial 24 weeks of follow-up and were assessed annually for up to 5 years for clinical signs of liver disease progression and evidence of virological relapse.

A total of 366 sustained responders (SRs) and 201 patients who were not sustained responders (NSRs) entered the study and were followed for a mean of 248 and 232 weeks, respectively; 85% of SRs and 77% of NSRs competed 3 years of follow-up, while 62% and 50%, respectively, completed 5 years.

Results

• 4 SR subjects experienced virological relapse during the 5-year follow-up period (2 at year 1, 1 at year 2, and 1 at year 5).

• The Kaplan-Meier estimate for continued sustained virological response over 5 years was 99%.

• Of the 192 SRs with normal ALT values at the end of the initial 24 week follow-up period, 174 (91%) maintained normal values throughout the 5-year follow-up period.

• Most abnormal ALT values were only slightly above the upper limit of normal (ULN), and the highest elevation remained below 5 × ULN.

• 1 NSR patient experienced liver disease progression (bleeding varices), compared with none in the SR group.

• 5 SR subjects died during follow-up, but all of the deaths were unrelated to liver disease progression or treatment toxicities (prostate cancer, lung cancer, myocardial infarction, coronary embolism, ventricular fibrillation).

• Serious adverse events were reported for 64 subjects, 3 of which were considered possibly related to pegylated interferon plus ribavirin (thyroid cancer, peripheral neuropathy + hypertension, ureter stones).

Conclusion

For patients responding to [pegylated interferon + ribavirin] therapy, SVR at 24 weeks post treatment predicts long-term clearance of HCV," the investigators concluded.
They added that these results "suggest that successful treatment (SVR) of HCV with interferon (± ribavirin) leads to a clinical cure of this chronic disease."

USC Keck School of Medicine, Los Angeles, CA; Medical School of Hannover, Hannover, Germany; Henry Ford Hospital, Detroit, MI; Scripps Clinic, La Jolla, CA; Universitaetsklinikum, Duesseldorf, Germany; Evgenidion Hospital, Athens, Greece; University of Iowa, Iowa City, IA; Weill Medical College of Cornell University, New York, NY; Hospital Ramon y Cajal, Madrid, Spain; University of Miami, Miami, FL; University of Pittsburgh, Pittsburgh, PA; St. Louis University, St. Louis, MO; Hopital Beaujon, Clichy, France; Minnesota Clinical Research Center, Plymouth, MN; Duke University, Durham, NC; Schering Plough Research Institute, Kenilworth, NJ.

5/30/08

Reference
K Lindsay, MP Manns, SC Gordon, and others. Clearance of HCV at 5 year follow-up for peginterferon alfa-2b with or without ribavirin is predicted by sustained virologic response at 24 weeks post-treatment. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract S1001.