Re-treatment of Chronic Hepatitis C Patients Who Do Not Respond to Pegylated Interferon Alfa-2b (PegIntron)

Many people with chronic hepatitis C virus (HCV) infection, especially those with HCV genotype 1, do not achieve a sustained response to their first course of standard-of-care treatment using pegylated interferon alfa-2a (Pegasys) plus ribavirin or pegylated interferon alfa-2b (PegIntron) plus ribavirin.

In a study published in the April 22, 2009 issue of the Annals of Internal Medicine, researchers evaluated use of pegylated interferon (peginterferon) alfa-2a plus ribavirin to re-treat prior non-responders to peginterferon alfa-2b.

The study, called REPEAT (REtreatment with PEgasys in PATients), was conducted at 106 international centers between September 2003 and February 2007. A total of 950 patients who were non-responders to 12 or more weeks of peginterferon-2b plus ribavirin were randomized and stratified by geographic region, HCV genotype, and histological diagnosis.

Participants received various treatment regimens: 360 mcg/week peginterferon alfa-2a for the first 12 weeks, then 180 mcg/week to complete 72 weeks (Group A; n = 317) or 48 weeks (Group B; n = 156), or else 180 mcg/wk peginterferon alfa-2a for the full 72 weeks (Group C; n = 156) or 48 weeks (Group D; n = 313). All patients also received 1000 or 1200 mg/day weight-adjusted ribavirin.

The primary outcome measurement was a sustained virological response (SVR), defined as undetectable (< 50 IU/mL) HCV RNA 24 weeks after the end of treatment.

Results

• The SVR rates were 16% for Groups A, 7% for Group B, 14% for Group C, and 9% for Group D.

• Extended treatment duration increased SVR rates: 16% for the 72 week arms (Groups A and C) vs 8% for the 48 week arms (Groups B and D).

• 21% of patients in Groups A and B and 13% of those in Groups C and D achieved complete viral suppression (HCV RNA < 50 IU/mL) at week 12.

• SVR rates were 49% (77 of 157) for patients with complete viral suppression at week 12 and 4% (32 of 719) for patients without complete viral suppression at this time point.

In conclusion, the study authors wrote, "Re-treating nonresponders to therapy with peginterferon alfa-2b plus ribavirin for 72 weeks significantly increases SVR rates compared with re-treating them for 48 weeks."

"The overall SVR rate was low," they continued, "but patients who are most likely to respond to re-treatment can be identified at week 12."

The editors of the Annals of Internal Medicine noted that a limitation of this study was that non-responders to a previous course of peginterferon alfa-2a (Pegasys) plus ribavirin were not evaluated.

Center for Liver Diseases, University of Chicago Hospitals, Chicago, IL; Centre de Recherche Biologique Bichat-Beaujon, Hôpital Beaujon, Clichy, France; Liver and Pancreas Institute of Kansas City, Kansas City, MO; University of Bologna, Bologna, Italy; Saint Louis University School of Medicine, Saint Louis, MO; University of Rio de Janeiro, Rio de Janeiro, Brazil; University of Pennsylvania, Philadelphia, PA; University of Palermo, Palermo, Italy; Hospital La Paz, Madrid, Spain; J.W. Goethe University Hospital, Frankfurt, Germany; IST, Mannheim, Germany; Roche, Nutley, NJ; Roche, Basel, Switzerland.


DM Jensen, P Marcellin, B Freilich, and others. Re-treatment of Patients with Chronic Hepatitis C Who Do Not Respond to Peginterferon Alfa-2b. Annals of Internal Medicine 150(8): 528-240. April 21, 2009. (Abstract).