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Peg Interferon Discussion-Marty

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  • 2byteme@bellsouth.net
    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 30, 2000
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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?

      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

      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.
      2000;32(suppl 2):29.
      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.
      2000;32:348A.
      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.
      2000;32:348A.
      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.
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