WIN-R Study Demonstrates Efficacy of Shorter PegIntron and Ribavirin Regimen in Hepatitis C Patients with Genotype 2 or 3

For patients infected with hepatitis C virus (HCV) genotype 2 or 3, a shorter, 24-week course of therapy with peginterferon alfa-2b (PegIntron) in combination with ribavirin, USP (Rebetol) was as effective as a 48-week course, and was better tolerated by patients, according to findings of the WIN-R study presented at the 41st EASL in Vienna, Austria this week [1]. 

Cornell/Columbia Medical Centers, which conducted the study, released a statement on the results of the trial. Following are excerpts from the university’s announcement. (A link to the abstract by the study authors appears in the references at the close of this article).

Importantly, the shorter 24-week regimen was also associated with a low rate of relapse – only 6 percent in genotype 2 patients and 10 percent in genotype 3 patients, which was consistent with a finding of 5 percent and 12 percent, respectively, in the longer 48-week regimen. 

Relapse is defined as patients with undetectable hepatitis C virus levels at the end of treatment who subsequently have detectable virus 24 weeks after treatment.

“These findings are important because they confirm the effectiveness of a shorter course of peginterferon alfa-2b and ribavirin combination therapy for genotype 2 and 3 patients in a real-world community setting and reinforce current treatment practice,” said Robert S. Brown Jr., M.D., M.P.H., lead investigator of the WIN-R genotype 2/3 sub-study, chief of clinical hepatology and medical director of the Center of Liver Disease and Transplantation at New York-Presbyterian Hospital/Columbia University Medical Center. “Lessening treatment duration can benefit patients in a number of ways, including by limiting side effects, which can be significant with hepatitis C therapy.  However, the risk of relapse is a concern when shortening treatment of the hepatitis C virus. 

“No physician wants to tell a patient the devastating news that after completing a difficult course of HCV therapy and thinking it has been successful, they have relapsed. The low rate of relapse seen in WIN-R can give physicians added confidence that 24 weeks of peginterferon alfa-2b and ribavirin combination therapy is sufficient to optimize the chance of cure in their genotype 2 and 3 patients,” said Ira M. Jacobson, M.D., principal investigator of the WIN-R study and coauthor of the genotype 2/3 sub-study, and chief of the division of gastroenterology and hepatology at New York-Presbyterian Hospital/Weill Cornell Medical Center in New York City. 

WIN-R Study Findings in HCV Genotype 2/3 Patients

In the WIN-R study, 4,913 patients were randomized to receive weight-based PegIntron
(1.5 mcg/kg weekly) in combination with Rebetol given either as a flat dose (800 mg daily) or a weight-based dose (800 mg, 1,000 mg, 1,200 mg or 1,400 mg daily for body weights of less than 65 kg, 65 to 85 kg, 86 to 105 kg, or 106 to 125 kg, respectively). 

Patients were treated for 48 weeks (genotype 1) or 24 weeks (genotype 2 or 3).  Patients in the treatment arms were evenly matched for gender, age, body weight, genotype, viral load and stage of liver fibrosis.  A total of 1,829 genotype 2 and 3 patients were enrolled and randomized in the study.

Investigators found that in genotype 2 and 3 patients the 24-week course of therapy was as effective as 48 weeks and better tolerated.  In the weight-based Rebetol dosing arms, the rate of sustained virologic response (SVR) [2] was 68 percent for the 24-week course compared to 60 percent for the 48-week course, with the lower percentage attributable to more missing follow-up data. 

In the 24-week arm, patients with genotype 2 had a higher SVR and lower relapse rate than those with genotype 3 (72 percent vs. 60 percent and 6 percent vs. 10 percent, respectively).  Investigators concluded that higher, weight-based doses of ribavirin appear to be necessary to achieve similar SVR rates in genotype 3 patients. 

Multivariate analyses showed that genotype 2, less advanced fibrosis and 24 weeks of therapy were significant predictors of SVR.  Safety and rates of drug discontinuation were similar between the treatment groups.

A short-coming in conducting large community-based HCV studies such as WIN-R, as opposed to registration trials with their more intensive monitoring capabilities, is the tendency for a high rate of patients to miss their follow-up viral testing (PCR) visit 24 weeks after treatment ends due to the limited ability of many sites to conduct rigorous monitoring of patients once they have received their final treatment dose. 

In the WIN-R study overall, 13.1 percent (164/1,256) of patients in the weight-based dose group and 13.7 percent (163/1,193) of patients in the fixed-dose group who were responders at the end of treatment were lost to follow up and subsequently counted as treatment failures under a strict intent-to-treat (ITT) analysis.

WIN-R was an investigator-initiated clinical study supported by Schering-Plough Corporation and monitored by Schering-Plough Research Institute as part of a post-marketing commitment to the U.S. Food and Drug Administration (FDA).  PegIntron and Rebetol are registered trademarks of Schering-Plough.

05/02/06

Source
Cornell/Columbia Medical Centers. WIN-R Study Demonstrates Efficacy of Shorter PEG-INTRON and REBETOL Regimen in Hepatitis C Patients with Genotype 2 or 3 Virus. Press Release. April 29, 2006.

References

1.  R S Brown, I M Jacobson, N Afdahl, and others (the WIN-R Study Group). DIFFERENCES IN TREATMENT OUTCOME TO ANTIVIRAL THERAPY BASED ON GENOTYPE AND VIRAL LOAD IN HEPATITIS C GENOTYPES 2 AND 3 IN THE WIN-R TRIAL Abstract 41 (Oral). 41^st EASL. April 26-29, 2006. Vienna, Austria.

2.  SVR is defined as undetectable virus (HCV RNA) levels 24 weeks after the end of treatment.