Ask the Experts: When Are PEG-IFNs Indicated?
- Ask the Experts on . . .
When Are PEG-IFNs Indicated?
When is pegylated interferon indicated in the
management of the patient with hepatitis C?
Cristiane Alves Villela Nogueira, MD
from Paul J. Pockros, MD, 10/26/00
Currently, there are no pegylated interferons
(PEG-IFN) approved for use in the United States.
Therefore, the indications for their use have not yet
been determined. However, results of recent trials
suggest that PEG-IFNs will likely be indicated in
treatment-naive patients and in a number of
difficult-to-treat groups, including those with
hepatitis C virus (HCV) genotypes 1 and 4, cirrhotics,
patients with renal impairment, the elderly, and
The poor sustained response seen in three times a week
multiple dosing of interferon (IFN)-alpha may be
related to the inability of this regimen to maintain
therapeutic levels of the drug and thereby exert
sustained viral pressure. The PEG-IFNs are
compounds that have prolonged absorption, decreased
renal clearance, and reduced immunogenicity. They have
a longer half-life compared with regular, unmodified
IFNs and, thus, may be given once weekly with
excellent therapeutic levels. A recent study
demonstrated a sustained virologic response rate (SVR;
ie, percentage of patients whose HCV RNA was below the
level of detection) of 36% in previously untreated
noncirrhotic patients with hepatitis C. The adverse
events and laboratory abnormalities associated with
PEG-IFN appear to be similar to those seen with
standard IFN therapy and less than those seen with
combination IFN/ribavirin therapy.
Pegylated interferon seems to offer improved efficacy
in cirrhotic patients as well, and 2, large
multicenter phase III trials recently confirmed these
findings.[4,5] The 2 pegylated compounds that will
likely be approved for clinical use in the United
States are not equivalent, although they are both more
effective than unmodified IFN. Although results were
obtained in separate comparative studies rather than a
head-to-head trial, thus making it difficult to
compare the compounds directly, in my opinion, the
40-kd branched PEG-IFN-alpha 2a (PEGASYS) appears to
have demonstrated better efficacy than the 12-kd
PEG-IFN alpha 2b (Peg-Intron) in all patients (39% SVR
vs 25% SVR, respectively) and in patients with HCV
genotype I (28% SVR vs 14% SVR, respectively).[4,5]
Both drugs however, showed at least twice the efficacy
of that of their standard unpegylated IFN-alpha 2a or
IFN-alpha 2b counterpart.[4,5] The improved
effectiveness and ease of use of these PEG-IFNs will
almost guarantee that they will supersede our current
arsenal of IFNs. Additionally, the combination of
PEG-IFN and ribavirin is currently under study and
results will likely demonstrate further improvement in
efficacy with this regimen as well.
Because the 40-kd PEG-IFN is primarily cleared
hepatically, the dosage seems to be unaffected by
renal impairment. And, in support of this, results
of a single-dose study showed that the influence of
impaired renal function on the pharmacokinetics of
this drug were sufficiently small such that no dose
adjustment should be required in this patient
population. Furthermore, recent data suggest that
no adjustment in dosing will be required in elderly
adults either. The 40-kd PEG-IFN-alpha 2a also
appears to have enhanced efficacy in difficult to
treat groups, such as blacks and patients who are
HCV genotype 4.
Reddy KR, Wright TL, Pockros PJ, et al. Efficacy and
safety of pegylated interferon alpha 2a compared with
interferon alpha 2a in noncirrhotic patients with
chronic hepatitis C. Hepatology. 2000. In press.
Shiffman M, Pockros PJ, Reddy RK, et al. A controlled,
randomized multicenter, descending dose phase II trial
of pegylated interferon alfa-2a (PEG) vs standard
interferon alfa-2a (IFN) for treatment of chronic
hepatitis C [abstract]. Gastroenterology.
Heathcote EJ, Shiffman ML, Cooksley, et al. A
controlled, randomized, multi-center phase II, III
trial of pegylated alpha 2a versus standard interferon
alpha 2a for treatment of patients with chronic
hepatitis C and cirrhosis [abstract]. Hepatology.
Zeuzem S, Feinman SV, Rasenack J, et al. Evaluation of
the safety and efficacy of once-weekly peginterferon
alfa-2a (PEGASYS) for chronic hepatitis C. A
multi-national, randomized study [abstract]. J
Hepatol. 2000;32(suppl 2):29.
Trepo C, Lindsey K, Niederau C, et al. Pegylated
interferon alfa-2b (PEG-INTRON) monotherapy is
superior to interferon alfa-2b (INTRON A) for the
treatment of chronic hepatitis C. J Hepatol.
Sulkowski M, Reindollar R, Yu J. Pegylated interferon
alfa-2a (PEGASYS) and ribavirin combination therapy
for chronic hepatitis C: a phase II open-label study.
Gastroenterology. 2000;118(suppl 2):A950.
Modi MW, Fulton JS, Buckman DK, et al. Clearance of
pegylated (40KD) interferon alpha 2a (PEGASYS) is
primarily hepatic [abstract]. Hepatology.
Martin P, Mitra S, Farrington K, et al. Pegylated
(40KD) interferon alpha 2a (PEGASYS) is unaffected by
renal impairment [abstract]. Hepatology. 2000;32:370A.
Martin NE, Modi MW, Reddy KR, et al. Characterization
of pegylated (40KD) interferon alpha 2a (PEGASYS) in
the elderly [abstract]. Hepatology. 2000;32:348A.
Shiffman ML, Fromm H, Mills P, et al. Enhanced
efficacy of pegylated (40KD) interferon alpha 2a
(PEGASYS) compared with interferon alpha 2a (Roferon
A) for chronic hepatitis C in blacks [abstract].
Sherman M, Dusheiko J, Haussinger D, et al. Superior
virologic response in genotype IV chronic hepatitis C
patients treated with pegylated (40KD) interferon
alpha 2a (PEGASYS) compared with standard interferon
[abstract]. Hepatology. 2000;32:348A.
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