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Ask the Experts: When Are PEG-IFNs Indicated?

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    Ask the Experts on . . . When Are PEG-IFNs Indicated? ... Question When is pegylated interferon indicated in the management of the patient with hepatitis C?
    Message 1 of 1 , Oct 29, 2000
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      Ask the Experts on . . .
      When Are PEG-IFNs Indicated?

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      Question
      When is pegylated interferon indicated in the
      management of the patient with hepatitis C?
      Cristiane Alves Villela Nogueira, MD


      Response
      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
      blacks.
      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.[1] 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.[2] 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.[1]

      Pegylated interferon seems to offer improved efficacy
      in cirrhotic patients as well,[3] 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.[6]

      Because the 40-kd PEG-IFN is primarily cleared
      hepatically, the dosage seems to be unaffected by
      renal impairment.[7] 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.[8] Furthermore, recent data suggest that
      no adjustment in dosing will be required in elderly
      adults either.[9] The 40-kd PEG-IFN-alpha 2a also
      appears to have enhanced efficacy in difficult to
      treat groups, such as blacks[10] and patients who are
      HCV genotype 4.[11]


      References
      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.
      1999;116:A1275.
      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.
      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.
      2000;32:29.
      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.
      2000;32:371A.
      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].
      Hepatology. 2000;32:348A.
      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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