Peginterferon alpha-2a plus ribavirin versus peginterferon alpha-2b
plus ribavirin in naive patients with chronic hepatits C virus infection:
results of a prospective randomized trial.
Posting Date: April 28, 2008
Prospective, randomized, single center, open-label study
Summary of Key Conclusions
Higher sustained virologic response (SVR) with peginterferon alfa-2a vs peginterferon alfa-2b
therapy in treatment-naive chronic hepatitis C patients
Effect largely observed in genotype 1 HCV patients with high HCV RNA
Different response patterns in genotype 2 vs 3 suggest to evaluate these groups of patients
separately
Adverse effects similar between 2 groups
Higher number of peginterferon alfa-2b patients discontinued treatment
Background
2 well-accepted treatment options for chronic hepatitis C
Peginterferon alfa-2a plus ribavirin
Peginterferon alfa-2b plus ribavirin
Efficacy comparisons of 2 peginterferon formulations only across studies to date
Some pharmacokinetic differences have been identified
Current study compared the efficacy and safety of peginterferon alfa-2a vs peginterferon alfa2b in treatment-naive HCV-infected patients
Schematic of Study Design
Eligibility
Inclusion criteria
> 18 years of age
Detectable HCV RNA
ALT > 1.5 x upper limit of normal within previous 6 months
Liver biopsy within previous year
Exclusion criteria
Previous treatment experience
HIV or HBV coinfection
Other cause of chronic liver disease or any severe chronic disease
History of decompensation
Alcohol use within 6 months
Severe hypertension
Depression
Neoplasia
Active diabetes
Pregnancy or lack of birth control use
Hemoglobin < 12 g/dL
Neutrophil count < 1.5 x 109/L
Platelet count < 70 x 109/L
Baseline Characteristics
Characteristic
Peginterferon alfa2a
(n = 160)
Peginterferon alfa2b
(n = 160)
50.6
58.8
51.3 (10.3)
48.9 (11.3)
570 (0.37-8550)
604 (0.20-10800)
2.63 (1.76)
2.41 (1.32)
20.6
16.3
1
55.6
57.5
2
30.6
31.3
3
11.3
10.6
4
2.5
0.6
Male, %
Mean age, yrs (SD)
Median HCV RNA x 103 IU/mL
(range)
Mean ALT, x upper limit of
normal (SD)
Cirrhosis, %
HCV genotype, %
SD, standard deviation.
Description of Current Analysis
Intent to treat analysis
Primary endpoint: SVR, defined as HCV RNA negative at 24 weeks after end of treatment
Detection by qualitative PCR with sensitivity of 50 IU/L
Patients also evaluated for end of treatment response
Main Findings
Higher SVR in peginterferon alfa-2a arm than peginterferon alfa-2b arm
Greatest disparity in SVR rates among genotype 1/4-infected patients
Trend toward higher SVR rates with peginterferon alfa-2a in patients with genotype
2
Similar rates with genotype 3
Higher rates of SVR with peginterferon alfa-2a in patients with high baseline HCV
RNA
Parameter, %
Peginterferon
alfa-2a
(n = 160)
Peginterferon
alfa-2b
(n = 160)
P Value
68.7
54.4
.008
Genotypes 1/4
54.8
39.8
.04
Genotypes 2/3
88.1
74.6
.046
Genotype 2
91.8
77.8
.062
Genotype 3
77.8
70.6
.921
HCV RNA <
500,000 IU/mL
68.4
65.7
.73
HCV RNA
≥ 500,000 IU/mL
69.0
46.2
.002
Cirrhosis
42.4
46.2
NA
83.7
64.3
< .0001
Genotypes 1/4
75.3
49.5
< .0003
Genotypes 2/3
95.5
85.1
.04
SVR
End of treatment response
NA, not available.
Peginterferon alfa-2a, male sex, absence of cirrhosis, and genotypes 2/3 significant predictors
of SVR
Other Outcomes
Adverse effects similar between groups
18.7% of patients had anemia
2.5% of patients neutropenia
4.1% of patients had thrombocytopenia
Higher number of peginterferon alfa-2b patients had treatment interruptions
14.0% and 13.4% of genotype 1/4 and 2/3 patients, respectively, treated with
peginterferon alfa-2b discontinued therapy vs only 3.2% and 1.5% of patients, respectively,
treated with peginterferon alfa-2a
Reference
Ascione A, De Luca M, Tartaglione MT et al. Peginterferon alpha-2a plus ribavirin versus peginterferon
alpha-2b plus ribavirin in naive patients with chronic hepatits C virus infection: results of a prospective
randomized trial. Program and abstracts of the 43rd Annual Meeting of the European Association for the
Study of the Liver; April 23-27, 2008; Milan, Italy. Abstract 990.