Type of Pegylated Interferon More Effective for Treating Chronic
interferon plus weight-adjusted ribavirin is standard therapy
for chronic hepatitis C, but there has not been consensus about
the relative benefits of Pegasys (Roche/Genentech) and PegInton
(Schering-Plough). Past research has produced conflicting findings,
and data have not always been strictly comparable due to regimen
differences such as varying doses of ribavirin, which helps prevent
relapse after the end of therapy.
Interferon alpha used for hepatitis C treatment is a genetically
engineered version of a natural human cytokine (chemical messenger).
It works by enhancing immune system responses against HCV.
Pegylated interferon is attached to polyethylene glycol (PEG),
which makes it last longer in the body (allowing injections once
instead of 3 times weekly). Pegasys and PegIntron have different
shapes and sizes (40 kDa vs 12 kDa molecular weight), which influences
their pharmacokinetic properties and may affect how well they
the first new study, Maria Grazia Rumi from Università
degli Studi in Milan and colleagues compared the safety and efficacy
of the 2 pegylated interferons in treatment-naive chronic hepatitis
C patients stratified by HCV
The study included 431 participants. About half had hard-to-treat
HCV genotypes 1 or 4, and about 19% had liver cirrhosis, another
characteristic associated with poorer treatment response.
were randomly assigned (1:1) to receive 180 mcg/week Pegasys or
1.5 mcg/kg/week PegIntron for 24 weeks (genotypes 2 or 3) or 48
weeks (genotypes 1 or 4). In accordance with the drugs' differing
prescribing instructions, genotype 1 and 4 Pegasys recipients
received 1000-1200 mg/day weight-adjusted ribavirin and genotype
2 and 3 Pegasys recipients received a fixed dose of 800 mg/day;
in contrast, all PegIntron recipients received 800-1200 mg/day
weight-adjusted ribavirin regardless of genotype.
an intent-to-treat analysis, the overall sustained virological
response (SVR) rate 24 weeks after completing treatment was
significantly higher in the Pegasys group compared with the
PegIntron group (66% vs 54%, respectively; P = 0.02).
the 222 patients with HCV genotypes 1 or 4, the corresponding
SVR rates were 48% vs 32%, respectively (P = 0.02).
the 143 patients with genotype 2, the SVR rates were 96% vs
82%, respectively (P = 0.01) (there were too few genotype
3 patients to permit a separate analysis).
Pegasys and PegIntron groups had similar rates of treatment-related
serious adverse events (1% in both) and discontinuation due
to adverse events (7% vs 6%, respectively).
a logistic regression analysis, use of Pegasys was an independent
predictor of SVR (odds ratio 1.88).
Based on these findings, the study authors concluded, "Although
the 2 regimens showed a similar safety profile, the [pegylated
interferon alpha-2a]-based treatment yielded significantly more
SVR than [pegylated interferon alpha-2b]."
the second study, Antonio Ascione from Cardarelli Hospital
in Naples and colleagues compared the safety and efficacy of Pegasys
versus PegIntron in 320 previously untreated chronic hepatitis
About 18% of participants had cirrhosis at baseline, and about
55% had high HCV RNA viral load (> 500,000 IU/mL).
Again, participants were randomly assigned (1:1) to receive 180
mcg/week Pegasys or 1.5 mcg/kg/week PegIntron for 24 weeks (genotypes
2 or 3) or 48 weeks (genotypes 1 or 4). In this study, however,
all participants -- regardless of genotype -- received ribavirin
at doses 1000 mg/day if they weighed < 75 kg (about 165 lb)
or 1200 mg/day if heavier.
an intent-to-treat analysis, more patients overall achieved
SVR in the Pegasys group compared with the PegIntron group
(68.8% vs 54.4%; P = 0.008).
genotype 1 or 4 patients, the corresponding SVR rates were
54.8% vs 39.8%, respectively (P = 0.04).
genotype 2 or 3 patients, the SVR rates were 88.1% vs 74.6%,
respectively (P = 0.046).
participants without cirrhosis (all genotypes combined), SVR
rates were 75.6% with Pegasys vs 55.9% with PegIntron (P =
patients with cirrhosis, however, SVR rates were statistically
similar (42.4% vs 46.1%, respectively; P = 0.774).
patients with high baseline HCV RNA, SVR rates were again
higher in the Pegasys compared with the PegIntron group (75.6%
vs 55.9%; P = 0.005).
patients with low baseline viral load, SVR rates did not statistically
differ (68.4% vs 65.7%, respectively; P = 0.727).
"In patients with chronic HCV infection, treatment with peginterferon
alfa-2a plus ribavirin produced a significantly higher SVR rate
than treatment with peginterferon alfa-2b plus ribavirin,"
the investigators concluded.
an accompanying editorial Stefan Zeuzem from J.W. Goethe University
Hospital in Frankfurt, Germany, offered a perspective on the findings
from these 2 trials in the context of prior research.
"Owing to greater variations in peak-to-trough ratios for
peginterferon alfa-2b than peginterferon alfa-2a, HCV RNA levels
tend to fluctuate more (at least within the initial 4 weeks of
therapy) in patients treated with peginterferon alfa-2b than in
those treated with peginterferon alfa-2a," he noted.
One previous large study, the IDEAL
trial sponsored by Schering-Plough, included more than 3000
HCV genotype 1 patients treated with Pegasys or PegIntron according
to the drugs' respective label directions (i.e., the ribavirin
dose was not consistent). In that study, Pegasys recipients had
a higher end-of-treatment response rate (64.4% Pegasys vs 53.2%
PegIntron) but PegIntron recipients had a lower relapse rate (31.5%
Pegasus vs 23.5% PegIntron) so the sustained response rates ended
up being statistically similar (40.9% Pegasys vs 39.8% PegIntron).
A recent systematic review by the Cochrane Collaboration of randomized
clinical trials comparing the 2 pegylated interferons, which included
a meta-analysis of SVR rates in 8 trials with a total of 4293
participants, found that Pegasys was slightly but significantly
more effective than PegIntron (relative risk 1.10; P = 0.004),
with similar results for all subgroups; adverse event profiles
"Taken together, since the publication of the pivotal phase
3 trials for peginterferon alfa-2a and alfa-2b in combination
with ribavirin, it took another 8 years to characterize the pharmacodynamic
differences between the 2 drugs in detail," Zeuzem wrote.
"At the dawn of new direct antiviral drugs against HCV we
need now to investigate how important the observed differences
between the peginterferons (and other long-acting interferons
such as albumin interferon) are in combination with HCV NS3/4A
protease and NS5B polymerase inhibitors."
It also remains to be determined whether one form of pegylated
interferon works better than the other in HIV/HCV coinfected patients,
who tend to respond less well to interferon-based therapy than
people with HCV alone.
Study 1: A.M. Migliavacca Center for Liver Disease, Fondazione
IRCCS Maggiore Hospital, Mangiagalli e Regina Elena, Università
degli Studi di Milano, Milan, Italy; Unit of Epidemiology and
Biostatistics, San Carlo Borromeo Hospital, Milan, Italy.
Study 2: Department of Gastroenterology, Liver Unit and Pathology
Units, Cardarelli Hospital, Napoli, Italy; Department of Medicine,
Centre for Liver Disease, Fatebenefratelli Hospital, Napoli, Italy;
Gastroenterology Unit, IRCSS de Bellis, Castellana Grotte, Italy.
M Rumi, A Aghemo, GM Prati, and others. Randomized Study of Peginterferon-alpha2a
Plus Ribavirin vs Peginterferon-alpha2b Plus Ribavirin in Chronic
Hepatitis C. Gastroenterology 138(1): 108-115 (Abstract).
A Ascione, MD Luca, MT Tartaglione, and others. Peginterferon
Alphalfa-2a Plus Ribavirin Is More Effective Than Peginterferon
Alphalfa-2b Plus Ribavirin for Treating Chronic Hepatitis C Virus
Infection. Gastroenterology 138(1): 116-122 (Abstract).
S Zeuzem. Do Differences in Pegylation of Interferon Alfa Matter?
(Editorial). Gastroenterology 138(1): 34-36 (Free
full text). January 2010.