The Pegasys Advantage

Study says combination with ribavirin works better against hepatitis C than interferon alfa 2b and ribavirin

The combination of Pegasys, a new generation pegylated interferon for the treatment of hepatitis C, and ribavirin "provides a considerable clinical advantage" over interferon alfa 2b and ribavirin, says a new study published in the New England Journal of Medicine.

    The randomized controlled clinical trial conducted in 81 centers worldwide sought to determine if Pegasys [peginterferon alfa 2a (40 KD)] plus ribavirin is more effective than interferon alfa 2b plus ribavirin or Pegasys monotherapy in the treatment of chronic hepatitis, which affects more than 170 million people worldwide. The study involved 1, 121 patients from Australia, Austria, Belgium, Brazil, Denmark, Finland, France, Germany, Greece, Italy, Mexico, The Netherlands, Norway, Portugal, Spain, Switzerland, Taiwan and the USA.

    The authors noted that Pegasys plus ribavirin significantly enhanced the sustained virological responses (defined as undetectable virus) regardless of viral genotype or viral load when compared to interferon alfa 2b plus ribavirin. The study noted "significantly higher" overall sustained viral response of 56 percent compared to 44% with interferon alfa-2b plus ribavirin. For most difficult to treat cases, genotype I and high viral levels, there was a substantial increase in sustained virological response of 41 percent versus 33 percent, the study said. Also, patients with cirrhosis had an increased sustained virological response of 43 percent compared with 33 percent for interferon alfa 2b plus ribavirin. Patients with genotypes 2/3 obtained a sustained virological response of 76 percent versus 61 percent.

    The results indicate that "this new combination offers patients a better chance of being cured," said lead author, Dr. Michael Fried, associate professor of medicine and director of clinical hepatology at the University of North Carolina at Chapel Hill.

    Superior Efficacy

    The overall safety profiles of the three treatment regimens were similar. However, the study found that side effects typically associated with the use of interferons (including flu like symptoms and depression) were reported less frequently with Pegasys combination therapy. The authors said this "was a particularly important observation demonstrating that superior efficacy can be achieved with peginterferon alfa 2a plus ribavirin without corresponding increases in adverse events most commonly associated with interferon based therapies."

    By week 12 of a 48 week treatment course, 86 percent of patients treated with the Pegasys combination had achieved an early virological response. An early response was indicative of achieving a sustained response, which occurred in 65 percent of patients. In contrast, the few patients who did not achieve an early response were unlikely to achieve a sustained response.

    "Early prediction of virological response is a valuable tool for physicians," said Dr. Fried. "It can help identify who is likely to succeed with this treatment. Importantly, it can also help clinicians to determine whether to discontinue therapy for those not responding, saving patients the side effects and cost of additional therapy," he added. But he cautioned that this must be considered on an individual basis.

    Roche, manufacturer of Pegasys, said the drug is different by design and provides significant benefit over standard interferon therapy in patients infected with HCV of all genotypes. The benefits of Pegasys derive from its new generation large 40 kilodalton polyethylene glycol (PEG) construction, which is preferentially distributed to the liver-the primary site of infection-and allows true seven day viral suppression. Pegasys is administered once weekly in an easy to use pre filled syringe with a fixed 180 mcg starting dose for all patient types.

**"Early prediction of virological response is a valuable tool for physicians. It can help identify who is likely to succeed with this treatment. Importantly, it can also help clinicians to determine whether to discontinue therapy for those not responding, saving patients the side effects and cost of additional therapy."

-Dr. Fried