ENHANCED VIROLOGICAL RESPONSE TO TREATMENT WITH 40 KDA PEGINTERFERON ALFA-2A
(PEGASYS) IN PATIENTS PREVIOUSLY UNRESPONSIVE TO TREATMENT WITH INTERFERON
Reported by Jules Levin
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
www.natap.org for ongoing coverage of the AASLD liver meeting.
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-naïve 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 HCVä 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 therapy.
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
--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%, respectively.
--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.