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Win-R Study: Ribavirin Weight-Base Dosing in High Weight Patients; Treatment Responses to PegIntron/RBV for Elderly Patients and by Patient Ethnicity
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"New Data from Largest U.S. Hepatitis C Trial Provide Insights Into Optimizing Treatment for Patient Populations Traditionally Considered Difficult to Treat"
October 31, 2006 - 5:58 AM
Source: NewYork-Presbyterian/Weill Cornell Medical Center
Community-Based WIN-R Study Shows Significantly Better Outcomes with Weight-Based Dosing
BOSTON, Oct. 30 /PRNewswire/ -- 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(R), Schering-Plough) and ribavirin (REBETOL(R), 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. The findings were reported in four separate presentations here at the 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
"These WIN-R findings help us better understand how to optimize hepatitis C treatment for the different types of patients we see everyday in community practice," said principal investigator Ira M. Jacobson, M.D., Vincent Astor Professor of Clinical Medicine at Weill Cornell Medical College, and Chief of the Division of Gastroenterology and Hepatology at NewYork-Presbyterian Hospital/Weill Cornell Medical Center in New York City. "These results, in the large number of patients who participated in this study, provide a wealth of information that physicians can use with confidence to help improve treatment outcomes in their hepatitis C patients."
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,(1) 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.(2) SVR is the standard measure of treatment success.
New WIN-R Data at AASLD 2006
-- Patient weight (Dr. Ira Jacobson and colleagues).(3) Historically,
studies have shown that heavier patients with hepatitis C virus (HCV) infection are less likely to achieve an SVR with antiviral therapy.(4) 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%) [with 1400 mg ribavirin]. 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 ribavirin.
-- Elderly patients (Dr. Steven Flamm and colleagues).(5) 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 (n=69) were more likely than any other age group to achieve an SVR (57%), patients older than 65 (n=55) 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 ribavirin based upon age alone.
-- Patient ethnicity (Dr. Bradley Freilich and colleagues).(6) 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.(7) 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 ribavirin. 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).(8) Patients with HCV genotype 2 or 3 (G2 or G3) generally respond better to treatment than patients with genotype 1,(9) 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.
About the WIN-R Study
In the WIN-R study, 4913 patients were randomized to receive weight-based peginterferon alfa-2b (1.5 mcg/kg weekly) in combination with ribavirin 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 with HCV genotype 1 were treated for 48 weeks; those with genotype 2 or 3 were treated for 48 weeks or 24 weeks. Patients in the treatment arms were evenly matched for gender, age, body weight, genotype, viral load and stage of liver fibrosis.
Serving with Dr. Jacobson as co-principal investigator of the WIN-R study is Robert S. Brown Jr., M.D., M.P.H., Associate Professor of Medicine and Surgery at Columbia University College of Physicians and Surgeons, and Chief of Clinical Hepatology and Medical Director of the Center of Liver Disease and Transplantation at NewYork-Presbyterian Hospital/Columbia University Medical Center. Drs. Jacobson and Brown are also co-directors of New York-Presbyterian Healthcare System's Liver Clinical Trials Network (LCTN).
Dr. Jacobson also is Medical Director of the Center for the Study of Hepatitis C, a unique interdisciplinary center established jointly by The Rockefeller University, NewYork-Presbyterian Hospital and Weill Cornell Medical College in New York City.
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). PEG-INTRON and REBETOL are registered trademarks of Schering-Plough.
(1) Jacobson I, Brown Jr. R, Freilich B, et al. Weight based ribavirin
dosing (WBD) increases sustained viral response (SVR) in patients with chronic hepatitis C (CHC): final results of the WIN-R study, a U.S. community-based trial. Hepatology. 2005;42(suppl 1):749A.
(2) Sustained virologic response (SVR) is defined as undetectable virus (HCV-RNA) levels in the blood at 6 months after the end of therapy.
(3) Jacobson IM, Brown Jr RS, Freilich B, et al. Response to peginterferon alfa-2b and ribavirin for chronic hepatitis c in patients with body weight greater than or equal to 125 kg: results from the WIN-R trial. Poster presentation at: 57th annual meeting of the American Association for the Study of Liver Disease, Boston, October 27-31, 2006.
(4) Bressler BL, Guindi M, Tomlinson G, Heathcote J. High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Hepatology. 2003;38:639-644.
(5) Flamm SL, Jacobson IM, Brown RS, et al. Pegylated interferon alfa-2b + ribavirin is equally efficacious and well tolerated in patients >65 years old in comparison to other age groups: subanalysis of a randomized, controlled study (WIN-R Trial). Poster presentation at: 57th annual meeting of the American Association for the Study of Liver Disease, Boston, October 27-31, 2006.
(6) Freilich B, Hu K, Jacobson IM, et al. Prospective analysis of
sustained virologic response to peg-interferon alfa-2b and ribavirin
treatment in Asian and Hispanic patients with chronic hepatitis C:
results from the WIN-R trial. Poster presentation at: 57th annual
meeting of the American Association for the Study of Liver Disease,
Boston, October 27-31, 2006.
(7) Hepburn MJ, Hepburn LM, Cantu NS, Lapeer MG, Lawitz EJ. Differences in treatment outcome for hepatitis C among ethnic groups. Am J Med. 2004 Aug 1;117(3):163-8.
(8) Brown Jr RS, Jacobson IM, Afdhal N, et al. Risk factors for relapse in genotype 3 high viral load patients with hepatitis c in the WIN-R
trial. Poster presentation at: 57th annual meeting of the American
Association for the Study of Liver Disease, Boston, October 27-31,
2006.
(9) Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.
(10) Ince N, Wands JR. The increasing incidence of hepatocellular
carcinoma. N Engl J Med 1999 March 11;340:10.
(11) Centers for Disease Control and Prevention. Recommendations for prevention and treatment of hepatitis C virus (HCV) and HCV-related chronic disease. MMWR Weekly Report 1998 Oct. 16;1.
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