LOS ANGELES -- Researchers who participated in the WIN-R trial, the largest hepatitis C study ever conducted in U.S. patients, reported key factors affecting treatment outcomes in five data presentations at the Digestive Disease Week (DDW) annual meeting, and provided important insights for optimizing treatment with PEG-INTRON® (peginterferon alfa-2b) and REBETOL® (ribavirin, USP) combination therapy for patients with chronic hepatitis C virus (HCV) infection, a potentially deadly liver disease. WIN-R (Weight-Based Dosing of PEG-INTRON and REBETOL), a community-based trial, involved more than 4,900 patients at 225 centers across the United States.
In the WIN-R study, patients achieved significantly better outcomes overall with weight-based dosing of ribavirin in combination with PEG-INTRON as compared to the combination using a flat dose of ribavirin. These results included significantly higher rates of sustained virologic response (SVR),1 the standard measure of treatment success, for patients overall (44 percent vs. 41 percent; p=0.01), and for patients with HCV genotype 1, the most difficult type to treat (34 percent vs. 29 percent; p=0.004). The study also showed that, for patients infected with HCV genotype 2 or 3, a shorter, 24-week course of therapy was as effective as the standard 48-week course, with better tolerability.2
Researchers presenting WIN-R data at DDW examined the effect specific predictive factors had on the likelihood of patients achieving an SVR, including factors such as HCV genotype and pretreatment viral load, degree of fibrosis or cirrhosis, cigarette smoking and prior HCV treatment experience at the study sites.
"These WIN-R findings help us better understand how to optimize hepatitis C treatment for our patients and how certain patient characteristics affect response to therapy in real-world community settings," said principal investigator Ira M. Jacobson, MD, Vincent Astor professor of Clinical Medicine at Weill Medical College of Cornell University, and Chief of the Division of Gastroenterology and Hepatology at New York-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 not only help confirm what many treating physicians have come to know in their everyday practice, but also add exciting new information that gives physicians added confidence that they can optimize the chance for cure in their hepatitis C patients."
Treating U.S. HCV patients can be especially challenging as they tend to have disease characteristics associated with poor treatment response, including a high prevalence of HCV genotype 1, high viral load and advanced liver fibrosis (scar tissue). Other factors such as age, high body weight and African-American ethnicity also have been shown to be associated with poor response to treatment.
In the WIN-R study, 4913 patients were randomized to receive weight-based PEG-INTRON (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 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 Jacobson as co-principal investigator of the WIN-R study is Robert S. Brown Jr., MD, MPH, 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 New York-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).
Jacobson also is medical director of the Center for the Study of Hepatitis C, a unique interdisciplinary center established jointly by The Rockefeller University, New York-Presbyterian Hospital and Weill Cornell Medical College in New York City.
WIN-R is 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.
Hepatitis C is the most common blood-borne infection in America, affecting approximately 4 million people or about one in every 50 adults. Chronic hepatitis C can cause cirrhosis, liver failure and liver cancer. It has been estimated that at least 20 percent of patients with chronic hepatitis C develop cirrhosis, and a smaller percentage of patients with chronic disease develop liver cancer. Patients with chronic hepatitis C and related cirrhosis are 100 times more likely to develop liver cancer than uninfected persons.3 About half of all cases of primary liver cancer in the developed world are caused by hepatitis C, and hepatitis C related liver disease is now the leading cause for liver transplants.4
1) Sustained virologic response (SVR) is defined as undetectable virus (HCV-RNA) levels in the blood at 6 months after the end of therapy.
2) Jacobson I, Brown Jr. R, Freilich B, Afdahl N, Kwo P, Santoro J, Becker S, Wakil A, Pound D, Godofsky E, Strauss R, Bernstein D, Flamm S, Bala N, Araya V, Davis M, Monsour H, Vierling J, Regenstein F, Balan V, Dragutsky M, Epstein M,. Herring RW, Rubin R, Galler G, Pauly MP, Griffel LH, Brass CA, the WIN-R Study Group. 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. Oral presentation at: 56th Annual Meeting of the American Association for the Study of Liver Diseases, San Francisco, CA, Nov 11-15, 2005.
3) Ince N, Wands JR. The increasing incidence of hepatocellular carcinoma. N Engl J Med 1999 March 11;340:10.
4) 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.
Source: New York-Presbyterian Hospital/Weill Cornell Medical Center