Peg Interferon Discussion-Marty
- 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.
1.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.
2.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. 1999;116:A1275.
3.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. 1999;30:316A.
4.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.
5.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. 2000;32:29.
6.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.
7.Modi MW, Fulton JS, Buckman DK, et al. Clearance of
pegylated (40KD) interferon alpha 2a (PEGASYS) is
primarily hepatic [abstract]. Hepatology. 2000;32:371A.
8.Martin P, Mitra S, Farrington K, et al. Pegylated (40KD)
interferon alpha 2a (PEGASYS) is unaffected by renal
impairment [abstract]. Hepatology. 2000;32:370A.
9.Martin NE, Modi MW, Reddy KR, et al.
Characterization of pegylated (40KD) interferon alpha 2a
(PEGASYS) in the elderly [abstract]. Hepatology.
10.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]. Hepatology.
11.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.