24 Weeks Treatment with Peginterferon Alfa-2b (PegIntron)
plus Ribavirin Is Efficacious in Patients with Chronic HCV Genotype 1 and
Low Pretreatment HCV RNA Levels
Previous studies using
standard
interferon and ribavirin combination therapy have suggested
that patients infected with HCV-1 and a low pretreatment
HCV-RNA level can be treated for 24 weeks without
compromising
sustained
virologic response rates.
The aim of the present study was to investigate this schedule in the era of pegylated interferon alfa plus ribavirin.
Patients chronically infected with HCV-1 (n=235) and a screening viremia </=600,000IU/mL (real-time PCR) were treated with peginterferon alfa-2b (PegIntron) 1.5mug/kg subcutaneously once weekly plus ribavirin 800-1400mg/day based on body weight for 24 weeks.
Results
End-of-treatment and
sustained virologic response rates were 80 and 50%, respectively.
The 48-week historical
control (Manns et al., Lancet 2001;358:958-65) had similar
end-of-treatment (74%) but higher sustained virologic response rates (71%).
This difference was due
to a high virologic relapse rate after 24 weeks of therapy (37%) compared
with the historical control (4%).
A subset of patients
who had undetectable serum HCV-RNA at treatment week 4, however, achieved
similar sustained virologic response rate (89%) as in the control group
(85%).
In conclusion, the authors write, “HCV-1 infected patients with a low baseline HCV-RNA concentration who become HCV-RNA negative at week 4 may be treated for 24 weeks without compromising sustained virologic response rates.”
Department of Medicine,
12/16/05
Reference
http://www.hivandhepatitis.com/hep_c/news/2005/ad/121605_b.html
Treatment of Genotype 1 Chronic Hepatitis C: Increased
Sustained Virological Response with High-dose RBV and Epoetin
Anemia is the most important side effect of ribavirin (RBV), leading often to dose reductions and premature treatment discontinuations. RBV dose reductions also are associated with decreased SVR.
The use of epoetin (EPO) [Procrit] has been proven to reduce anemia and the need for RBV dose reductions. Study results presented at the 56th AASLD by Shiffman and colleagues show that the use of EPO also increases sustained virological response (SVR) when given with high doses of RBV to patients infected with HCV genotype 1.
Naïve patients infected with HCV-1 were randomly assigned to one of three treatment groups:
Group 1: pegylated interferon (pegIFN)-a-2b (1.5 mg/Kg/week) + RBV 13.3 mg/Kg/day (N=48)
Group 2: pegylated interferon (pegIFN)-a-2b (1.5 mg/Kg/week) + RBV 13.3 mg/Kg/day + EPO (N=49)
Group 3: pegylated interferon (pegIFN)-a-2b (1.5 mg/Kg/week) and RBV 15.2 mg/Kg/day +EPO (N=49)
In groups 2 and 3, EPO was given at onset of treatment if hemoglobin values were < 15 g/dL, or later on as soon as hemoglobin levels dropped below that threshold. EPO dose was initially 40,000 U/week, and doses were increased to 60,000 U/week if no response was obtained.
Groups were similar in age (median 48 years), proportion of African Americans (36-43%) and body weight (median 82.4 Kg). Only a minority of patients had cirrhosis, and although without statistically significant differences, it was more common in group 2 (8%) than in groups 1 (4%) and 3 (2%).
The table summarizes the results of the study:
|
Group 1 RBV 13.3/kg |
Group 2 RBV 13.3/kg+EPO |
Group 3 RBV 15.2/kg+EPO |
|
| EVR |
67% |
53% |
65% |
| ETR |
48% |
46% |
55% |
| SVR |
27% |
24% |
45%* |
| Relapses** |
36% |
40% |
8%* |
|
% RBV dose reduction D/C anemia Hb <10g/dL Hb <8.5 g/dL |
40% 4% 34% 2% |
10%*** 2% 9% 2% |
31% 0% 6% 0% |
* p<0.05 vs. groups 1 and 2
** % of responders at the end of treatment
*** p<0.05 vs. group 1
D/C: discontinuations
No significant differences were found in early virological response (EVR) or end-of-treatment response (ETR), but there were less relapses and higher proportion of SVR in the high RBV dose group compared to the others. SVR were higher in the high RBV dose group than in the other groups regardless of race ( African-American, 31% vs. 18%; non-African American, 53% vs. 30%).
In summary, the use of EPO significantly decreased the frequency of anemia, and the need for RBV dose reductions and premature discontinuations.
The use of higher doses of RBV (1,000-1,600 mg/day) decreased relapses and therefore increased SVR across all body weights and races in patients infected with HCV genotype 1.
These results are encouraging and suggest that the use of high doses of RBV should be evaluated in large clinical trials.
11/23/05
Reference
M L
Shiffman and others.
Treatment of chronic hepatitis C viris (HCV)
genotype 1 with peginterferon alfa-2b (PEGIFN),
high weight based dose ribavirin (RVN) and
epoetin alfa (EPO)
enhances sustained virologic response (SVR).
Abstract 55. 56th annual
meeting of the American Association for the Study of Liver Diseases (56th
AASLD). November 11-15, 2005.
http://www.hivandhepatitis.com/2005icr/aasld/docs/112305_a.html
|
Short-term Treatment Duration for HCV Genotypes 2 and 3 Patients
It is well known that
HCV genotypes 2 and 3 patients have significantly higher
sustained
response rates (SVR) to treatment compared to
genotypes 1 and 4 patients. Prior studies have also
demonstrated that 12-14 weeks treatment is effective in genotype 2 or 3 HCV
patients who become HCV
undetectable after 4 weeks of therapy
rapid
virologic response (RVR) or “Super
Responders (SR)”.
In this retrospective study, 2 data sets of patients from Italy and Norway were pooled with the objective of identifying predictors of sustained virological response (SVR), RVR and relapse after short term treatment (12-14 weeks or 24 weeks) with peginterferon alfa-2b (PegIntron) (1.0, n=281 or 1.5 μg/kg, n=122) plus ribavirin (800-1200 mg). Dosing depended on negative or positive HCV RNA at week 4.
The primary endpoint was undetectable HCV-RNA 24 weeks after therapy (SVR).
Results
SVR was
obtained in 313/403 patients (78%).
SVR
differed between cases with or without RVR (85% vs 62%), mild or bridging
fibrosis/cirrhosis (82% vs 67%), absent/mild or moderate/severe steatosis
(84% vs 72%), HCV-2 or -3 (81% vs 73%) low or high viremia (80% vs 67%).
RVR, mild
fibrosis, and HCV-2 were independent predictors of SVR.
RVR was
obtained in 274/403 (68%) patients, 163/242 (67%) HCV2, and 111/161 (69%)
HCV-3.
Patients
with RVR had, as compared to those without RVR, more frequently low grade
steatosis (72% vs 64%), mild fibrosis (70% vs 63%, and high PegIFN dose (78%
vs 64%).
RVR was
independent of viral load.
absence of
severe fibrosis independently predicted RVR.
In RVR
patients, SVR was achieved in 85% of both HCV-2 and HCV-3.
Virologic
relapse was observed in 29/274 RVR patients (10.6%), and was more frequently
observed among those with low ALT levels (14% vs 5%), high viremia (14% vs
6%), and severe fibrosis (18% vs 8%).
Peg-IFN
dose,
steatosis and genotype were not associated with risk of
relapse.
Severe
fibrosis and low
ALT
were independent predictors of relapse.
In conclusion, the authors write, “In HCV-2 or -3, the HCV RNA status after 4 weeks of therapy may guide treatment duration. Short treatment duration is effective in both HCV-2 and -3 patients with RVR, but those with severe fibrosis are less likely to experience both RVR and SVR, and more frequently relapse off therapy.”
11/18/05
Reference
A Andriulli and others. SHORT-TERM TREATMENT DURATION FOR HCV-2
AND HCV-3 INFECTED PATIENTS WITH CHRONIC HEPATITIS. Abstract 1234.
Abstracts of the annual meeting of the
American Association for the Study of Liver Diseases (56th AASLD).
November 11-15, 2005. San Francisco, CA.