Dose and Duration of PegIntron plus Ribavirin Is Not as Effective as Standard
Therapy for Genotype 2 and 3 Hepatitis C Patients
therapy for chronic hepatitis C virus (HCV)
infection produces a high sustained
response rate -- generally in the 70% to 80% range -- in people with easier-to-treat
HCV genotypes 2 or 3. But
therapy is costly and associated with difficult side effects, leading researchers
to study reduced doses and shorter treatment durations.
the 44th Annual Meeting of the European Association for
the Study of the Liver (EASL 2009) last month in Copenhagen, M. Manns and
an international team of colleagues reported findings from the REDD 2/3 Trial,
showing that a reduced treatment duration or a decreased dose of pegylated interferon
produced inferior results compared with standard therapy in treatment-naive genotype
2 or 3 patients in Europe and Asia.
The recommended standard treatment
for patients with HCV genotype 2 or 3 is pegylated interferon plus ribavirin for
24 weeks. Shorter-duration treatment of such patients has been "largely unsuccessful
compared with standard-duration treatment," the investigators noted as background.
However, the implications of reduced pegylated interferon dosing in this group
The aim of the present study was to evaluate the effect of
shorter treatment duration and reduced doses of pegylated
interferon alfa-2b (PegIntron) on sustained virological response (SVR; continued
undetectable HCV RNA 24 weeks after completion of therapy) and relapse rates.
This open-label study began in 2003 as a "real world" investigator-initiated
trial conducted in Germany by Hep-Net. In January 2005, Schering-Plough assumed
sponsorship, and the population was expanded in the REDD 2/3 trial to include
patients at additional sites in Poland, Israel, India, Indonesia, Malaysia, Singapore,
In total, 347 patients were from the original Hep-Net cohort
and 335 were from the expanded REDD 2/3 cohort. Overall, about 65% were men and
the mean age was about 40 years. Most (80%) had HCV genotype 3, while the rest
had genotype 2; about half had high (> 600,000 IU/mL) baseline HCV viral
load. People coinfected with HIV or hepatitis B were excluded.
patients were randomly assigned to receive either the standard dose of 1.5 mcg/kg/week
PegIntron for the usual 24 weeks, a lower dose of 1.0 mcg/kg/week PegIntron for
24 weeks, or the standard dose of 1.5 mcg/kg/week for only 16 weeks. In addition,
all participants received 800-1200 mg/day weight-adjusted ribavirin.
primary endpoint was non-inferiority between the standard therapy arm and the
reduced dose and reduced duration arms.
Overall, in an intent-to-treat (ITT) analysis, participants who received the reduced
dose and shorter duration of treatment had lower SVR rates than those who received
66.5% with 1.5 mcg/kg/week for 24 weeks;
64.3% with 1.0 mcg/kg/week for 24 weeks;
56.6% with 1.5 mcg/kg/week for 16 weeks.
58.6% with 1.5 mcg/kg/week for 24 weeks;
60.0% with 1.0 mcg/kg/week for 24 weeks;
47.4% with 1.5 mcg/kg/week for 16 weeks.
REDD 2/3 Cohort:
74.6% with 1.5 mcg/kg/week for 24 weeks;
68.8% with 1.0 mcg/kg/week for 24 weeks;
66.1% with 1.5 mcg/kg/week for 16 weeks.
Asian patients responded somewhat better than whites, but the difference in SVR
rates did not reach statistical significance.
End-of-treatment response rates and SVR rates in a per-protocol (as-treated) analysis
were in line with ITT results.
Neither primary endpoint -- non-inferiority of lower dose or of shorter duration
-- was achieved.
Relapse rates were lower with 24 weeks of therapy compared with 16 weeks (17.8%
and 16.3% vs 29.3%, respectively).
Adverse events were similar regardless of treatment duration or PegIntron dose.
on these findings, the researchers stated that they were "statistically unable
to demonstrate" that the lower-dose pegylated interferon regimen is non-inferior
to the standard-dose regimen.
"This study of [genotype 2 or 3] patients,
most of whom were difficult-to-treat European and Asian patients, confirms that
pegylated interferon alfa-2b 1.5 mcg/kg/week for 24 weeks remains the most effective
treatment for all [genotype 2 or 3] patients," they concluded.
School of Hannover, Hannover, Germany; J.W. Goethe University Hospital, Frankfurt,
Germany; Dayanand Medical College & Hospital, Ludhiana, Punjab, India; Sourasky
Medical Center, Tel Aviv, Israel; University of Wuerzburg Medical Center, Würzburg,
Germany; Selayang Hospital, Selangor, Malaysia; Hebrew University-Hadassah Medical
Center, Jerusalem, Israel; University of Munich, Munich, Germany; Schering-Plough
Corporation, Kenilworth, NJ.
Manns, S Zeuzem, A Sood, and others. Reduced
Dose and Duration of Peginterferon Alfa-2b and Weight-Based Ribavirin in European
and Asian Genotype 2 and 3 Chronic Hepatitis C Patients (REDD 2/3 Trial).
44th Annual Meeting of the European Association for the Study of the Liver (EASL
2009). Copenhagen, Denmark. April 22-26, 2009.
Schering-Plough Highlights Hepatitis C Clinical Data Presentations at the European
Association for the Study of the Liver (EASL) Annual Meeting. Press release. April
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