Reported in four separate presentations at the 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)

Community-Based WIN-R Study Shows Significantly Better Outcomes with Weight-Based Dosing

New data from the WIN-R trial, the largest hepatitis C study ever conducted in U.S. patients, provide important insights into optimizing treatment with peginterferon alfa-2b (PEG-INTRON®, Schering-Plough) and ribavirin (REBETOL®, Schering-Plough) combination therapy in patient populations traditionally considered difficult to treat. Researchers evaluated results in specific patient groups to determine if characteristics such as age, ethnicity, body weight, hepatitis C genotype and viral load were independent predictors of response or medication tolerability.

WIN-R (Weight-Based Dosing of PEG-INTRON and REBETOL) was a community-based trial involving more than 4,900 patients at 225 centers across the United States. As reported last year at AASLD, the study showed peginterferon alfa-2b, in combination with weight-based ribavirin, resulted in better outcomes compared to flat-dosed ribavirin, including significantly higher rates of sustained virologic response (SVR) overall. SVR is the standard measure of treatment success.

New WIN-R Data at AASLD 2006
Patient weight (Dr. Ira Jacobson and colleagues). Historically, studies have shown that heavier patients with hepatitis C virus (HCV) infection are less likely to achieve an SVR with antiviral therapy. Results of the WIN-R study, however, showed that patients treated with peginterferon alfa-2b and weight-based ribavirin achieved consistent rates of SVR regardless of body weight. Even obese patients (those weighing 125 kg [275 lbs] or more) achieved SVR rates similar to all other patients in the study (45% vs. 44%). The heavier patients in WIN-R were much more likely to achieve an SVR with weight-based ribavirin than with flat-dosed ribavirin (64% vs. 25%). Obese patients also showed low rates of anemia, neutropenia and dose reductions, probably reflecting lower levels of ribavirin exposure with their larger body size. The authors concluded that obesity alone should not preclude consideration for hepatitis C treatment with peginterferon alfa-2b plus weight-based ribarivin.

Elderly patients (Dr. Steven Flamm and colleagues). Little data are available on how age affects the response to interferon-based therapies for hepatitis C because patients older than age 65 are ineligible for most clinical trials. This study showed that, while young adults age 18-25 years were more likely than any other age group to achieve an SVR (57%), patients older than 65 had a similar rate of SVR compared to all other age groups (46% vs. 44%, respectively). Although there were more adverse events among the older patients, the rate of serious adverse events and treatment drop-outs were the same or less than in the younger age groups. The authors concluded that older patients should not be denied access to hepatitis C therapy with peginterferon alfa-2b plus ribarivin based upon age alone.

Patient ethnicity (Dr.Bradley Freilich and colleagues). Past studies with standard interferon plus ribavirin therapy suggest that ethnic origin may be an important predictor of response, with SVR rates highest in Asian patients (61%), followed by Caucasian (39%), Hispanic (23%), and African-American (14%) patients. The WIN-R study included the largest dataset in Hispanic patients reported to date, and the results confirm that hepatitis C is challenging to treat in this population. Rates of SVR were significantly lower in Hispanic patients compared to Asian patients and Caucasian patients: 34% vs. 52% (p=0.0002) and 46% (p=0.0057), respectively. Among Hispanic patients, the best results were seen in those with hepatitis C genotype 2 or 3 and low baseline viral load who were treated with peginterferon alfa-2b plus weight-based ribarivin. Additional studies are required to identify factors that will improve SVR rates in this ethnic group.

Patients with HCV genotype 3 high viral load (Dr. Robert Brown and colleagues). Patients with HCV genotype 2 or 3 (G2 or G3) generally respond better to treatment than patients with genotype 1, and most studies have reported treatment responses in G2 and G3 patients as a single group. In WIN-R, these responses were examined separately, and showed that G2 patients achieved higher SVR rates (66% vs. 55%, p<0.0001) and lower relapse rates compared to G3 patients. G3 patients with high baseline viral load were more likely to relapse. While these findings suggest higher doses of ribavirin may benefit patients with hepatitis C genotype 3, additional research is needed to define the optimal strategy for lowering relapse rate in these patients.