Nancy A. Melville
Aug 27, 2013
Patients with chronic hepatitis C (HCV) in a traditionally difficult-to-treat population respond well to an interferon-free oral treatment regimen of sofosbuvir and ribavirin, according to research published in the August 28 issue of JAMA.
"Because treatment of HCV is evolving from an interferon-based combination therapy to an all-oral, interferon-free directly acting antiviral agent regimen, these results are encouraging and provide important information regarding the expected treatment responses in a population representative of the US epidemic," Anuoluwapo Osinusi, MD, MPH, from the National Institutes of Health, Bethesda, Maryland, write.
The 2-part, open-label phase 2 study involved 60 treatment-naive patients with HCV genotype 1. Among the participants, 83% were black, 66% were men, 23% had advanced liver disease, 48% had a body mass index of 30 kg/m2 or higher, 70% had HCV genotype 1a, and 62% had baseline HCV RNA levels of 800,000 or higher.
In the first part of the study, 10 patients with early to moderate liver fibrosis were treated with 400 mg/day sofosbuvir and ribavirin dosage based on weight for 24 weeks. The 50 participants in the second part of the study had all stages of liver fibrosis and were randomly assigned 1:1 to receive 400 mg sofosbuvir with either weight-based ribavirin or low-dose 600 mg/day ribavirin for 24 weeks.
Nine participants (90%) in the first part of the study achieved a sustained virologic response (SVR), defined as an undetectable HCV viral load for 24 weeks after the completion of treatment. In the second part of the study, 68% (95% confidence interval, 46% - 85%) of the patients in the weight-based dosage group achieved SVR for 24 weeks compared with 48% (95% confidence interval, 28% - 69%) of the patients in the low-dose group (P = .20).
Seven (28%) participants in the weight-based group and 10 (40%) participants in the low-dose group relapsed after completing treatment. Baseline factors most associated with relapse included male sex, advanced liver disease, and high baseline HCV RNA levels.
The most common adverse events included headache, anemia, fatigue, and nausea. Although most adverse events were described as mild to moderate, 7 patients developed grade 3 adverse events including anemia, neutropenia, nausea, hypophosphatemia, and cholelithiasis or pancreatitis. There were no deaths or discontinuation of treatment resulting from adverse events, and the combination regiment was considered safe and well-tolerated.
"This study demonstrates the efficacy of an interferon-free regimen in a traditionally difficult-to-treat population while exploring the reasons for treatment relapse," the authors write.
"As new direct-acting antiviral agent regimens are being evaluated, it is important that these studies involve populations most affected by the disease."
Interferon has, among its disadvantages, weekly injections and fatigue from influenza-like symptoms, and it is furthermore contraindicated in patients with HCV who have advanced liver disease, making the findings on the new all-oral regimen even more encouraging, said Michael Saag, MD, clinical director for the Center for AIDS Research and the Division of Infectious Diseases at the University of Alabama at Birmingham.
"Anything that allows these people to have success without the injection is an important step forward," he told Medscape Medical News.
Although the overall rate of 68% achieving sustained virologic response was lower than that observed in populations with more favorable treatment predictors, it is still higher than is typically seen in the black male population, Dr. Saag noted.
"The SVR rate in this population is usually in the 40% to 50% range, due to some [genotype differences], so 68% is relatively good," added Dr. Saag, who is also a spokesperson for the Infectious Disease Society of America's hepatitis task force. "I think we're on the verge of a very exciting revolution in HCV care, and this is the first of what I believe will be several landmark articles that will change how we approach the treatment of this disorder over the next 5 years."
The study was funded by the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the German Research Foundation. One coauthor has reported serving as research consultant for Roche Pharma and Novartis. One coauthor has reported serving on the Gilead and Merck Advisory Boards and as a speaker for Gilead. One coauthor has reported serving as a speaker for Merck and performing research funded by Vertex pharmaceuticals. One coauthor has reported being a member of the Regional Advisory Boards for Abbott and Gilead. Three coauthors are employees of Gilead Pharmaceuticals. Dr. Saag disclosed that he has consulted for Gilead Pharmaceuticals in the past but was not involved in the current study.
Sofosbuvir and Ribavirin for Hepatitis C Genotype 1 in Patients With Unfavorable Treatment Characteristics: A Randomized Clinical Trial (Journal of the American Medical Association-Abstract)
Investigational oral regimen for hepatitis C shows promise in NIH trial (NIH Press Release)