Pegasys and PegIntron for Chronic Hepatitis C Perform Similarly in IDEAL Study

By Liz Highleyman

The Phase 3b IDEAL trial, sponsored by PegIntron manufacturer Schering-Plough, enrolled 3070 previously untreated patients with HCV genotype 1 at 118 sites in the U.S. About 60% were men, the mean age was 48 years, about 70% were white, and nearly 20% were black.

Participants were randomly assigned to receive either 1.5 mg/kg/week (standard dose) or 1.0 mg/kg/week (low-dose) PegIntron plus 800-1400 mg/day weight-adjusted ribavirin, or else 180 mcg/week Pegasys plus 1000-1200 mg/day ribavirin for 48 weeks.

Results

	At week 48, patients in the Pegasys arms had a higher end-of-treatment response rate.
	Patients taking PegIntron, however, had a lower relapse rate:
	31.5% for Pegasys; 23.5% for standard-dose PegIntron; 20.0% for low-dose PegIntron.
	24 weeks after completion of therapy, SVR rates were statistically similar in all 3 arms:
	40.9% using Pegasys; 39.8% using standard-dose PegIntron (P=0.57 for Pegasys vs standard-dose PegInterferon); 38.0% using low-dose PegIntron (P=0.20 for standard-dose vs low-dose PegIntron).
	Estimated differences in response rates were -1.1% between Pegasys and standard-dose PegIntron and 1.8% between standard-dose and low-dose PegIntron.
	Across all arms, SVR rates were higher among patients who achieved rapid virological response at week 4 (86.2%) or early virological response at week 12 (78.7%).
	Regardless of treatment assignment, participants with advanced fibrosis or cirrhosis (stage F3-F4) were about half as likely to achieve SVR as those with mild-to-moderate fibrosis (about 20% vs about 40%).
	Likewise, in all arms, blacks had about half the SVR rate of whites.
	The safety profile was similar across all 3 arms, with about 10% of patients experiencing serious adverse events.

"In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b," the study authors concluded.

"When considering treatments for hepatitis C infection, patients and their doctors now have solid evidence that they can weigh both antiviral therapies equally for effectiveness, safety and tolerability," said co-principal investigator Mark Sulkowski from Johns Hopkins University Medical School in a press release issued by Schering-Plough.

Both regimens in the IDEAL trial were administered according to their label dosing directions, which allowed for a larger range of weight-based ribavirin doses with PegIntron. This discrepancy led to some criticism of the study, since higher doses of ribavirin have been shown to reduce the risk of HCV relapse (see article list below). The study investigators noted, however, that results were consistent when comparing patients taking similar ribavirin doses. In fact, participants who reduced their ribavirin doses due to anemia had a higher SVR rate than those who remained on the original full dose, contrary to prior studies.

For further information:

Media statements on preliminary IDEAL findings from Schering-Plough and Roche

IDEAL investigators John McHutchison and Mark Sulkowski discuss the design and rationale of the trial in the July 2008 issue of the Journal of Viral Hepatitis.

Hepatology expert Douglas Dieterich discusses the preliminary findings in the January-March 2008 issue of Liver Health Today.

How Ideal is the IDEAL Study? Two HCV activists discuss the IDEAL trial design.

7/28/09

Reference
JG McHutchison, EJ Lawitz, ML Shiffman, and others (for the IDEAL Study Team). Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection. New England Journal of Medicine. July 22, 2009 (Epub ahead of print). Free full text.

Other source
Schering-Plough. Hepatitis C infection: treatment options equally effective, likelihood of success known early on. Press release. July 22, 2009.