Pegasys in previous nonresponders to Interferon Alfa-2A
- NATAP - www.natap.org
Dallas, Nov 9-13
Reported by Jules Levin
ENHANCED VIROLOGICAL RESPONSE TO TREATMENT WITH 40 KDA
PEGINTERFERON ALFA-2A (PEGASYS) IN PATIENTS PREVIOUSLY
UNRESPONSIVE TO TREATMENT WITH INTERFERON ALFA-2A
editorial note from Jules Levin: there have been
several studies showing mostly relatively preliminary
data that shows patients who previously failed IFN+RBV
(Rebetron) could respond to Pegaylated IGN + RBV. This
study reports encouringing data that patients
previously not responding to IFN monotherapy can
respond to Pegasys alone. See resulrs below. See NATAP
website for ongoing coverage of the AASLD liver
Gerald Y Minuk, Univ of Manitoba, Winnipeg, MB Canada;
K. Rajender Reddy, Univ of Miami Sch of Medicine,
Miami, FL; Samuel S Lee, Univ of Calgary, Calgary, AB
Canada; E. Jenny Heathcote, Toronto Western Hosp,
Toronto, ON Canada; John O'Grady, King's Coll Sch of
Medicine, London Uk; Paul J Pockros, The Scripps
Clinic, La Jolla, CA; Mitchell L Shiffman, Med Coll of
Virginia, Richmond, VA; Nikolai V Naoumov, Univ Coll
London, London Uk; Farhad Sedarati, Jean Depamphilis,
Hoffmann-La Roche, Nutley, NJ
Background: Initial treatment with interferon (IFN) in
patients with chronic hepatitis C (CHC) results in
sustained virological response (SVR) in only about
8-20% of patients. Retreatment of IFN nonresponders
with a second, more intensive IFN course has yielded
disappointing results. 40 kDa peginterferon alfa-2a
(PEGASYS) is a modified form of IFN a-2a with an
optimized pharmacokinetic profile. In previous studies
treatment of IFN-na�ve CHC patients with 40 kDa
peginterferon alfa-2a results in SVRs of 30% to 39%
(Zeuzem S et al. N Engl J Med. 2000; 343:1666-1672).
The efficacy of 40 kDa peginterferon alfa-2a in
patients unresponsive to previous IFN therapy has not
yet been reported.
Objectives: To evaluate the efficacy of therapy with
40 kDa peginterferon alfa-2a in patients previously
unresponsive to IFN a-2a therapy.
Methods: All eligible patients had received 24-48
weeks of IFN a-2a tiw (3-6 MIU for the first 12 weeks
followed by 3 MIU for the remainder of treatment) for
the treatment of CHC, and had failed to achieve an SVR
(defined as undetectable HCV RNA using AMPLICOR HCV�
Test, v 2.0, lower limit of sensitivity 100 copies/mL,
24 weeks post-treatment). Patients who had not
tolerated IFN therapy were ineligible for retreatment.
Participating patients received 40 kDa peginterferon
alfa-2a 180 mg sc qw for up to 48 weeks and were
subsequently followed for 24 weeks. Patients failing
to show a 2 log10 decrease in HCV RNA between baseline
and week 12, and patients demonstrating detectable HCV
RNA despite 24 weeks of treatment, were considered
nonresponders and were prematurely discontinued from
Results. A total of 101 patients participated in this
study, including 92 end-of-treatment nonresponders
(EoT-NR) and 9 responder-relapse patients (RR).
Patients were predominantly male (73%) with a mean
weight of 78.3 kg and baseline viral load ranging from
0.04 x 10(6) to 40.9 x 10(6) copies/mL (54 patients
[54%] 2.0 x 10(6) copies/mL). Seventy-one patients
(71%) were infected with HCV genotype 1, and 29
patients (29%) had cirrhosis or bridging fibrosis.
--Among previously-treated EoT-NR, end-of-treatment
response (EoTR) and SVR were achieved by 33% and 19%
of patients, respectively.
--EoTR and SVR for RR patients were 89% and 33%,
--Importantly, among patients who did achieve
undetectable HCV RNA during the initial IFN treatment
regimen (ie, breakthrough and RR, n=31), EoTR and SVR
were found in 24 (77%) and 14 (45%) patients.
--Only 17 patients (24%) and 8 patients (11%) achieved
EoTR and SVR, respectively, among the 70 patients who
had never completely responded.
Conclusions: These results provide further evidence
that 40 kDa peginterferon alfa-2a is an optimized form
of IFN with improved efficacy over the parent
compound, particularly in traditionally
difficult-to-treat patient groups. Moreover, these
data suggest that retreatment with the combination of
40 kDa peginterferon alfa-2a and ribavirin may result
in even higher SVR in IFN nonresponders, especially
those who had achieved undetectable HCV RNA at some
point during the initial treatment period.
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