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Retreatment with PEG-Intron
Plus Ribavirin Shows Limited Benefit in Patients with Chronic Hepatitis C
Not Responding to Previous Treatment with Standard Interferon and Ribavirin
Abstract Summary
In interferon (IFN)
non-responders with chronic hepatitis C, retreatment with standard
interferons combined with ribavirin showed sustained virologic response
rates of 20-30%. Only limited data with conflicting results are available
concerning the efficacy of antiviral retreatment in patients not responding
to a previous treatment with standard interferons combined with ribavirin
The aims of the present
German trial were to evaluate efficacy and safety of a retreatment with PEG-Intron
(peginterferon alfa-2b) plus ribavirin in 240 patients (162 males, 78
females, mean age 45.5 years) not responding to previous antiviral treatment
with standard interferons combined with ribavirin.
Patients received PEG-Intron
100 mcg/week subcutaneously (sc) for 8 weeks followed by 50 mcg/week sc for
40 weeks in combination with ribavirin 800 mg/d for 48 weeks. Treatment was
discontinued in patients with detectable serum HCV RNA after treatment week
24.
A virologic
end-of-treatment response was achieved in 25/240 (10.4%) patients while
after a follow-up period of 24 weeks a sustained virologic response was
observed in 15/240 (6.3%) patients.
Patients infected with HCV
genotype non-1 were more likely to respond to antiviral retreatment than
patients infected with HCV genotype 1 (6.8% vs. 17%).
Conclusions:
antiviral retreatment with
PEG-Intron plus ribavirin in this flat and low dose showed only a limited
therapeutic efficacy in patients with chronic hepatitis C not responding to
previous treatment with standard interferons and ribavirin.
In these patients,
virologic response rates may be improved by administering PEG-Intron and
ribavirin bodyweight adapted or by the addition of other antiviral agents.
03/28/03
Reference
G Teuber and others.
CONTROLLED TRIAL WITH PEGYLATED INTERFERON-ALPHA2B PLUS RIBAVIRIN
RETREATMENT IN PATIENTS WITH CHRONIC HEPATITIS C NOT RESPONDING TO A
PREVIOUS ANTIVIRAL TREATMENT WITH STANDARD INTERFERONS COMBINED WITH
RIBAVIRIN. Abstract 3904.00.
Abstracts of the 38th
Annual Meeting of the European Association of the Study of the Liver
(EASL).
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Interim Results of Observational Study of Patients
Treated for Chronic Hepatitis C in France
Abstract Summary
The objective of this
observational study undertaken in France is to evaluate medical
practices for the treatment of chronic hepatitis C, and to assess the
observance, tolerance and efficacy of treatment outside clinical trials.
A sample of 50
specialists working in various settings participated in the study. All
consecutive patients who were prescribed authorized antiviral drugs were
enrolled. Demographic, epidemiological and virological data were
collected before treatment; follow up was made according to the habits
of each prescriber and included information on acceptability of the
treatment, dose modifications and their motive.
Between April 1st and
December 31st 2001, 578 patients were enrolled. The epidemiological,
virological and histological features of this group were similar to
those patients usually treated in France. Fifty-seven percent of
patients were treatment-naive, 16% were relapsers and 27% were
non-responders.
In 93% of cases,
treatment consisted of PEG-Intron (peginterferon alfa-2b/PEG-IFN) and
ribavirin at recommended doses: on average 1.4 mcg/kg of PEG-IFN and 13
mg/kg of ribavirin (16 to 11 mg/kg according to weight), irrespective of
gender, genotype and the existence of a previous treatment. All patients
have been followed at least 24 weeks.
Currently, 26 patients
(4.5%) have withdrawn from treatment; 110 (19%) patients have needed a
dose reduction of PEG-IFN and/or ribavirin. The acceptability of
treatment was good for 36% of patients, moderate or poor for 64% of
patients. The latter were more often women (44 vs 34%), they were older
(48.8 vs 44.6 yrs), for an equivalent dose of PEG-IFN and ribavirin.
Nevertheless, a dose reduction was prescribed in only 32% of patients
with moderate or poor tolerance, these patients receiving an average
higher initial dose of PEG-IFN (1.5 vs 1.4 mcg/kg, p=0.01).
Virological response
on treatment is now available for 299 patients: HCV RNA is undetectable
in 199 of them (66.6%, IC95% 61.2-71.9).
Conclusion:
The interim results of this observational study show that
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Most patients are
treated according to recommendations;
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Early withdrawal of
combination therapy remains rare; and
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Initial regimen is
often continued despite moderate or poor tolerance, which may be
important to attain virological response.
03/28/03
Reference
F Roudot-Thoraval and others. OBSERVATIONAL STUDY OF PATIENTS TREATED
FOR CHRONIC HEPATITIS C IN FRANCE. Abstract 3867.00.
Abstracts of the 38th
Annual Meeting of the European Association of the Study of the Liver
(EASL). |
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Early Virologic Response (EVR) at Week 8 Is More
Predictive of Sustained Response to Pegylated Interferon/Ribavirin
Therapy Than at Week 12
Abstract Summary
The aim of this study
was to assess the predictive value of early virologic response (EVR) in
patients receiving combination therapy with PEG-Intron (peginterferon
alfa-2b/PEG-IFN) plus ribavirin (RIBA).
The study
enrolled 81 patients: 43 naive and 38 previously treated (PT) with the
combination of Peg-IFN + RIBA were studied. Serum HCV RNA was measured
at baseline, weeks 1, 2, 4, 8, and 12, end of treatment and 24 weeks
after treatment by VERSANT HCV 3.0 (bDNA) assay and VERSANT HCV RNA
Qualitative Assay (HCV TMA). EVR was defined as ≥ 2 log drop of HCV RNA
with bDNA or undetectable HCV RNA with TMA during the first 12 weeks of
therapy.
The kinetic slope of
HCV RNA in SR was faster in naive than in PT patients.
The positive
Predictive Value (PPV) of SR according to EVR was 96%, 86%, 80% and 80%
in naive and 71%, 67%, 60% and 63% in PT at week 2, 4, 8 and 12,
respectively.
The negative
Predictive Value (NPV) of SR according to EVR was 25%, 9%, 0% and 0% in
naive and 19%, 20%, 18% and 17% in PT, at week 2, 4, 8 and 12,
respectively. PPV of SR according to TMA was 100%, 94%, 85% and 88% in
naive and 0%, 94%, 100% and 86% in PT at week 2, 4, 8 and 12,
respectively.
NPV of SR according to
TMA was 66%, 52%, 42% and 17% in naive and 48%, 41%, 28% and 23% in PT,
at week 2, 4, 8 and 12, respectively. The more accurate predictive
values for SR were TMA negative at week 4 or EVR at week 8.
Conclusions:
Prediction of SR assessed by ≥ 2 log drop (bDNA) or undetectable (TMA)
HCV RNA might be done as early as week 2 in naïve patients and as early
as week 4 in PT patients.
Prediction of no SR is
optimal at week 8 in naive and somewhat less accurate in PT patients.
Therefore treatment status should be considered when assessing patients
response to therapy.
03/28/03
Reference
M Martinot-Peignoux and others. EARLY VIROLOGIC RESPONSE (EVR) AT WEEK 8
IS MORE PREDICTIVE OF SUSTAINED RESPONSE (SR) TO PEGYLATED COMBINATION
THERAPY THAN AT WEEK 12. Abstract 4232.00.
Abstracts of the 38th Annual Meeting of the European
Association of the Study of the Liver
(EASL). |
Liver Fibrosis Regresses Better with PEG-Intron
and Ursodeoxycholic Acid Treatment Than with Spontaneous Recovery
Abstract Summary
Fibrosis and cirrhosis are
common complications of chronic liver diseases. An imbalance between
fibrogenesis and fibrolysis results in scarring of the liver parenchyma. In
the current study, researchers in Turkey investigated the possible
antifibrotic effectiveness of a newly modified interferon molecule
peginterferon a2b (PEG-IFN) which has better antiviral activity and
ursodeoxycholic acid (UDCA).
Liver fibrosis was
established on 60 male Sprague Dawley rats with CCl4 in 12 weeks. After
cessation of CCL4 Group I was left for spontaneous recovery. Group II was
treated with Peg-Intron (PEG-IFN 1.5 mcg/kg/week), Group III with UDCA 25
mg/kg/day and Group IV with combination of both drugs. All rats were killed
at week 16.
Histopathologic fibrosis
scores, tissue hidroxyprolin, TIMP-1 and MMP-13 levels were determined.
Apoptosis was detected by TUNEL staining. Fibrosis scores were lower in both
Group II, III and IV than Group I. Tissue hidroxyprolin levels were
significantly decreased in Group II, III and IV when compared to Group I,
respectively). Lower liver TIMP-1 and higher MMP-13 levels were measured in
Group II, III, and Group IV than Group I (p=0.007, p=0.05, p<0.001 for TIMP
and p<0.001, p=0.02, p<0.001, for MMP, respectively). Apoptosis was
significantly increased in Group II, III and IV when compared to Group I
(p<0.001, p<0.05, p<0.05, respectively). There was significantly higher
apoptosis in Group II than III and IV (p<0.06, p<0.05, respectively).
Conclusion:
Treatment with both peginterferon alfa-2b and ursodeoxycholic acid improves
CCL4 induced rat liver fibrosis. Significantly higher effects can be
obtained using these agents in combination.
03/28/03
Reference
I Tasci and others. LIVER FIBROSIS REGRESSES BETTER WITH PEGINTERFERON ALPHA
AND URSODEOXYCHOLIC ACID TREATMENT THAN SPONTANEOUS RECOVERY. Abstract
3321.00.
Abstracts of the 38th Annual Meeting of the European Association
of the Study of the Liver
(EASL).
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Pharmacokinetics of
Pegasys Compared to PEG-Intron in Treatment-Naïve Patients with Chronic
Hepatitis C
Abstract Summary
The currently
available pegylated interferon (PEG-IFN) formulations, PEG-IFN alfa-2a
(40KD, PEGASYS) and PEG-IFN alfa-2b (12KD, PEG-Intron), have different
pharmacokinetic profiles. The aim of this current study, conducted at
the University of Pavia, Italy, was to compare the pharmacokinetics of
the two PEG-IFNs in patients with chronic hepatitis C (CHC).
30 treatment naive
patients with CHC and persistently elevated ALT levels have been
randomized to receive 180 mcg PEGASYS once-weekly (n=16) or 1.0 mcg/kg
once-weekly of PEG-Intron (n=14). Serum concentrations of both PEG-IFNs
were measured at baseline and 24, 48, 120 and 168 hours after
administration using a quantitative sandwich ELISA (lower limit of
detection 125 pg/ml).
Serum concentration of
PEG-Intron achieved maximum levels at 24 hours after injection and
decreased rapidly until 120 hours. Drug was undetectable 120 and 168
hours after injection in 7 (50%) and 11 (78%) subjects, respectively. In
contrast, PEGASYS concentrations increased continuously overtime,
reaching maximum levels from 48 to 168 hours.
Conclusions:
The investigators conclude, “Our data demonstrate substantial
differences in plasma concentration profiles between PEGASYS and PEG-Intron.
Five days after injection concentrations of PEG-Intron are marginal or
undetectable, while those of PEGASYS remain stable overtime.
“These findings
suggest that PEG-Intron administration should be intensified to twice
weekly to avoid "blips" in viral replication. Differences in
pharmacokinetics could explain the differences observed in HCV
decay.”
03/24/03
Reference
R
Bruno and others. PHARMACOKINETICS OF PEGINTERFERON ALFA-2A (40KD,
PEGASYS) COMPARED TO PEGINTERFERON ALFA-2B (12KD, PEGINTRON) IN NAIVE
PATIENTS WITH CHRONIC HEPATITIS C (CHC). Abstract 4203.00.
Abstracts of the 38th Annual Meeting of the European
Association of the Study of the Liver
(EASL).
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