"Contrary to the prevailing belief that ribavirin dose reduction would lead to fewer people recovering from their infection, it actually increased the sustained viral response rate when reduction was used to manage treatment-related anemia," says Sulkowski, who attributes the onset of anemia as a sign that the body had sufficient ribavirin to fight off the infection.
"Our study shows that in infected people having difficulty tolerating standard dose therapy with peginterferon alfa, we can safely reduce their medication levels," he says.
The study also confirmed that blacks infected with hepatitis C, who comprised almost a fifth of all study participants, fare more poorly over the course of their disease, even with early therapy. They experienced roughly half the viral suppression rates of whites for every tested regimen. Sulkowski says the reasons for this remain unknown and subject to further research.
"As the largest study of its kind, our trial, called IDEAL, defines the current standard of care for treating hepatitis C infection," says study co-investigator David L. Thomas, M.D., director of infectious diseases at Johns Hopkins. "The study findings tell doctors how to treat hepatitis C infection today and underscore the importance of new therapies for the majority of people who cannot currently be cured." Thomas was one of four hepatitis C experts responsible for drafting the 2009 guidelines for the diagnosis, management and treatment of hepatitis C, recently published by the American Association for the Study of Liver Diseases, a national, professional society.
Sulkowski notes that comparative-effectiveness studies such as this one, despite their high cost and lengthy timelines, form the "fundamental backbone" for figuring out which one works best with newer treatments in the pipeline. Proposed next-stage therapies, primarily two hepatitis protease-inhibitors, boceprevir and teleprevir, are still in early testing, but can now be judged in comparison with what physicians know works best. Sulkowski says triple-combination drug therapies for hepatitis C could prove the current therapies more effective when used as a cocktail, similar to the antiviral regimens used to combat HIV.
In the latest study, recently infected people from across the United States were randomly assigned to one of three treatment groups, receiving either standard-dose peginterferon alfa-2b or peginterferon alfa-2a, each with ribavirin, or low-dose peginterferon alfa-2b, plus ribavirin. A majority of study participants were men in their 40s. All were treated for nearly a year and then monitored for another half-year. None had pre-existing conditions, such as HIV disease, another hepatitis infection, liver failure or liver cancer, or severe or active depression.
Researchers say the next phase of their research will profile people who do better on each different drug regimen to see if there are standout factors that predispose some to success on one drug over another.
They also plan further studies on drug-induced anemia to determine the effectiveness of synthetic erythropoietin, and whether or not EPO is more effective in some people than in others.
Funding support for this study, which took place between March 2004 and June 2006, was provided by the Schering-Plough Corporation of Kenilworth, N.J., the brand manufacturer and provider of study drugs ribavirin (also known as Rebetol, F.D.A. approved since 1996) and peginterferon alfa-b (or Peg Intron, approved in 2001). Peginterferon alfa-a (or Pegasys, approved in 2002) is manufactured by Hoffman La Roche Inc., of Nutley, N.J.
Sulkowski has received research support from and is a paid consultant to Schering-Plough. He has also received research support from and is a paid consultant to Roche. The terms of his arrangements are managed by The Johns Hopkins University in accordance with its conflict of interest policies. Co-principal investigator John McHutchison, from Duke University Medical Center in Durham, N.C., also has received research support from Schering-Plough.
Besides Sulkowski and Thomas, another Johns Hopkins researcher involved in this study was Stuart Ray, M.D.
Other study investigators included Eric Lawitz, M.D., at Alamo Medical Research, in San Antonio, Texas; Mitchell Shiffman, M.D., at Virginia Commonwealth University in Richmond; Greg Galler, M.D., at the Kelsey Research Foundation, in Houston; Jonathan McCone, M.D., at the Mount Vernon Endoscopy Center in Alexandria, Va.; Lisa Nyberg, M.D., at Kaiser Permanente San Diego Medical Center; William Lee, M.D., at the University of Texas Southwestern Medical Center, in Dallas; Reem Ghalib, M.D., at the Liver Institute at Methodist Dallas Medical Center in Texas; Eugene Schiff, M.D., at the University of Miami Center for Liver Diseases; Joseph Galati, M.D., at Liver Specialists of Texas, in Houston; Bruce Bacon, M.D., at Saint Louis University School of Medicine; Mitchell Davis, M.D., at the South Florida Center for Gastroenterology, in Wellington; and Pabak Mukhopadhyay, M.D.; Kenneth Koury, M.D.; Stephanie Noviello, M.D.; Lisa Pedicone, M.D.; Clifford Brass, M.D.; and Janet Albrecht, M.D., all of Schering-Plough.
Source: Johns Hopkins Medicine
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