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Frequent Dosing of Pegasys/Ribavirin Improves SVR Rate in Prior Non-responder
Genotype 1 HCV Patients with Severe Fibrosis
Once
weekly injection of pegylated interferon alfa in combination with ribavirin is
the current standard therapy for chronic hepatitis C. However, this regimen frequently
fails to clear infection in individuals with genotype
1 HCV.
Pegylated
interferon was designed as a longer-acting form of interferon that is injected
once weekly, as compared to 3 times weekly with the older conventional interferon
alfa. However, viral kinetics studies suggest that a rebound of viral replication
often occurs at the end of each week, before the next injection of pegylated interferon.
This rebound could be responsible for treatment failure and could theoretically
be prevented by more frequent peginterferon injections, the authors of the current
study hypothesized.
The patients were retreated
with pegylated interferon alfa-2a (Pegasys), 180 mcg administered every 5 days
for 12 weeks, followed by 180 mcg/week for an additional 36 weeks, in combination
with ribavirin (1,000 mg/day if weight < 75 kg and 1,200 mg/day if weight >
75 kg) for 48 weeks.
Results
6 of the 7 patients experienced an early virological response (EVR) (> 2 log
drop in HCV RNA at week 12) and an end-of-treatment response (ETR) (HCV RNA <
50 IU/mL).
The mean HCV RNA decline at week 12 was significantly more pronounced during the
second course of treatment (frequent pegylated interferon administration) than
during the first course (standard weekly administration): 3.66 +/- 1.35 log IU/mL
vs 0.70 +/- 0.46 log IU/mL, respectively.
Tolerance was similar to previous reports with weekly administrations of pegylated
interferon combined with ribavirin.
No dose interruptions or treatment discontinuations were required due to adverse
events or laboratory abnormalities.
Conclusion
In
conclusion, the authors wrote, "More frequent administrations of pegylated
interferon alfa in combination with ribavirin induce a sustained virological response
in a substantial proportion of patients with HCV genotype 1 infection and severe
fibrosis who did not respond to prior standard pegylated interferon/ribavirin
combination."
"Prospective, randomized controlled studies are
now needed to confirm the interest and evaluate the global results of frequent
pegylated interferon injections in difficult-to-treat patients with chronic hepatitis
C."
Patients
First
treatment: Viral load, baseline
First
treatment: Viral load, Week 12
First
treatment: Log viral load decline, baseline-Week 12
Second
treatment: Viral load, baseline
Second
treatment: Viral load, Week 12
Second
treatment: Log viral load decline, baseline-Week 12
1
6.34
5.08
1.26
6.42
<1.70
≥4.72
2
5.67
5.44
0.23
5.65
3.62
2.03
3
5.40
4.32
1.08
5.89
<1.70
≥4.19
4
6.42
6.25
0.17
6.27
> 1.70 <2.79
≥3.48
5
5.96
4.80
1.16
6.25
<1.70
≥4.5
6
5.39
4.92
0.47
5.31
<1.70
≥3.61
7
6.41
5.91
0.50
6.75
5.15
1.59
Hepatologie,
Hopital Henri Mondor, Creteil, France; Virology, Hopital Henri Mondor, Creteil,
France; Hopital Henri Mondor, Creteil, France; Public Health, Hopital Henri Nondor,
Creteil, France; Pathology, Hopital Henri Mondor, Creteil, France.
11/07/06
Reference C
Hezode, M Bouvier-Alias, F Roudot-Thoraval, and others. Efficacy and Safety of
Peginterferon alfa-2a Administrated Every Five Days in Combination with Ribavirin
in HCV Genotype-1-Infected Patients with Severe Fibrosis Not responding to Weekly
Administration of Peginterferon in Combination with Ribavirin. 57th AASLD. October
27-31, 2006. Boston, MA. Abstract 353.
6 of the 7 patients experienced an early virological response (EVR) (> 2 log
drop in HCV RNA at week 12) and an end-of-treatment response (ETR) (HCV RNA <
50 IU/mL). 
