Pegylated
interferon plus ribavirin is an effective therapy for many people
with chronic hepatitis C, but many others do not achieve a cure,
and the treatment can cause difficult side effects. Researchers,
therefore, have looked for ways to reduce the duration as much
as possible, and to discontinue treatment early if it appears
unlikely to produce a sustained response.
A 24 week course of pegylated interferon/ribavirin is standard
therapy for chronic hepatitis C patients with HCV genotypes 2
or 3, but those with hard-to-treat genotype 1 are usually treated
for 48 weeks. In Europe, however, shortening treatment to 24 weeks
is approved for people with low baseline viral load and rapid
virological response (RVR), or undetectable HCV viral load 4 weeks
after starting therapy.
Christoph Sarrazin and fellow investigators with the INDIV-2 Study
assessed whether more closely individualized treatment durations
according to baseline viral load and initial viral decline is
a feasible strategy.
This multicenter trial included more than 600 treatment-naive
genotype 1 patients in Germany. Participants were randomly assigned
to either undergo standard 48-week therapy or to receive pegylated
interferon-alfa-2b (PegIntron) plus ribavirin for individualized
treatment durations.
In the latter group, patients were treated for 24, 30, 36, 42,
48, 60, or 72 weeks, depending on whether they had high or low
baseline viral load (HCV RNA > or < 800,000 IU/mL) and undetectable
HCV RNA at week 4, 6, 8,12, or 24 using a highly sensitive TMA
viral load assay.
Results
 |
Overall
rates of sustained virological response (SVR) -- or continued
undetectable HCV RNA 24 weeks after treatment completion
-- were similar in the individualized and standard treatment
duration groups (53% vs 48%). |
|
SVR
rates were statistically similar between participants with
individualized treatment durations and patients who had
undetectable HCV RNA after the same durations but continued
therapy through week 48. |
|
Patients
in the individualized therapy group who achieved RVR at
week 4: |
| |
Treated for 24 weeks if low viral load: SVR 88% vs 93% in
standard duration control group;
Treated for 30 weeks if high viral load: SVR 86% vs 100%
in standard therapy group. |
|
Patients with first undetectable HCV RNA at week 6: |
| |
Treated for 30 weeks if low viral load: SVR 91% vs 77% in
standard therapy group;
Treated for 36 weeks if high viral load: SVR 85% vs 78%
in standard therapy group |
|
"
Patients with first undetectable HCV RNA at week 8: |
| |
Treated for 42 weeks if low viral load: SVR 72% vs 100%
in standard therapy group;
Treated for 48 weeks if high viral load: SVR 82% vs 88%
in standard therapy group. |
|
" Patients with first undetectable HCV
RNA at week 12 (complete early virological response, or
EVR): |
|
Patients
with first undetectable HCV RNA at week 24 and high viral
load, as well as those who first became undetectable at
week 30 and had low viral load, were treated for 72 weeks:
SVR 50%. |
Based on these results, the researchers concluded, "For treatment
of patients with chronic hepatitis C genotype 1 infection with
pegylated interferon [alfa-]2b and ribavirin complete individualization
and optimization of treatment duration is possible according to
baseline viral load and first time HCV RNA negativity at week
4, 6, 8, 12, and 24."
They also suggested that "Complete individualized treatment
durations may also be useful for STAT-C triple treatment schedules,"
referring to directly targeted agents such as HCV protease and
polymerase inhibitors that may shorten the required duration of
pegylated/interferon.
Medizinische Klinik 1, J. W. Goethe-University Hospital, Frankfurt/Main,
Germany; University Hospital Munich, Munich, Germany; Leberzentrum
Checkpoint, Berlin, Germany; University Hospital Ulm, Ulm, Germany;
Institut für Interdisziplinäre Medizin, Hamburg, Germany;
Johanna Etienne Krankenhaus, Neuss, Germany; Imterdisziplinäres
Facharztzentrum, Frankfurt/Main, Germany; University Hospital
Cologne, Cologne, Germany; University Hospital Freiburg, Freiburg
im Breisgau, Germany; University Hospital Würzburg, Würzburg,Germany;
University Hospital Mainz, Mainz, Germany; Klinikum Freising,
Freising, Germany; Essex Pharma, Munich, Germany; University Hospital
Leipzig, Leipzig, Germany.
4/23/10
Reference
C
Sarrazin, S Schwendy, B. Möller, and others.completely
individualized treatment durations (24, 30, 36, 42, 48, 60 or
72 weeks) with peginterferon-alfa-2b and ribavirin in HCV genotype
1-infected patients (INDIV-2 Study). 45th Annual Meeting of
the European Association for the Study of the Liver (EASL 2010).
Vienna, Austria. April 14-18, 2010. (Abstract).
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