Loading ...
Sorry, an error occurred while loading the content.

Does Amantadine Help Response to HCV Therapy? Pegasys Combinations

Expand Messages
  • claudine intexas
    NATAP www.natap.org ... Report from AASLD October 22-26, Dallas Jules Levin See NATAP web site for AASLD Updates previously posted & other treatment updates
    Message 1 of 1 , Aug 31, 2001
    • 0 Attachment

      Report from AASLD
      October 22-26, Dallas
      Jules Levin
      See NATAP web site for AASLD Updates previously posted
      & other

      -Does Amantadine Help Response to HCV Therapy?
      -Pegasys Combinations With Amantadine, Ribivarin +
      Amantadine, and
      Mycophenolate Acid

      Various studies have produced mixed results on whether
      improves standard HCV therapy. Some studies suggested
      amantadine may be
      affective in combination with IFN and RBV while other
      studies showed it
      not help. A number of researchers have concluded
      amantadine is not
      At this year's AASLD, the same mixed results were
      reported from several
      studies. But when considering the AASLD studies
      together I think they
      tend to
      suggest amantadine may have benefit, and deserve's a
      continuing look.
      reports are mostly from the AASLD program abstract

      Amantadine Appears Helpful in Non-Responders Receiving

      (Adinolfi, abstract 770)

      This first one-year randomized controlled pilot study
      in 65 persons
      chronic HCV took place in non-responders to previous
      therapy with IFN
      5-6 MU
      3 times per week. The study compared three regimens:
      group C received
      IFN 3
      MU daily for 1 month, then 3MU tiw (3x/wk) plus
      ribivarin, plus
      200 mg daily. Group B received the same IFN/RBV
      regimen without
      And Group A received standard therapy: IFN 3MU tiw
      plus RBV 1000 mg
      Study investigators reported: "�in a 6th month
      follow-up post
      sustained response was observed in 0% of patients in
      Groups A & B, and
      relapsed within the 2nd month after therapy. In the
      triple therapy
      Group C,
      response was 38% at 4th-6th month of follow-up".
      Authors reported
      therapy was safe and side effects were similar to
      those observed on
      Groups A
      & B. The authors reported 38% in Group C had cirrhosis
      and their
      rate at the end of treatment was 75% compared to 0%
      and 14% in Groups A
      & B,

      Randomization to Groups A, B and C was 26:26:13,
      respectively. Prior to
      starting study therapy, no differences were observed
      between Groups A,
      B, and
      C with respect to age (median 51, 51 and 50,
      respectively), cirrhosis
      25%, and 38%, respectively), genotype 1 (69%, 73%, and
      and levels of viral load. The response end-point was
      ALT normalization
      HCV viral clearance. At the end-of-treatment, response
      rate was for
      Group A
      27%, Group B 27%, and for Group C 69% (p<0.03). The
      response with
      respect to
      chronic HCV and cirrhosis was for Group A (28% and
      0%), B 32% and 14%),
      and C
      67% and 75%). Patients with Genotype 1 showed a
      response rate of 28%,
      and 56% for Groups A, B, and C, respectively. Response
      was observed
      between 3
      & 8 months in Groups A & B, whereas in Group C, 44% of
      within the first month of therapy. Again, 6 months
      after treatment
      (sustained response rate) 0% responders in Groups A &
      B, and all
      occurred in 2nd month post therapy. In the amantadine
      triple therapy
      response was 38% at 4-6 months of follow-up.

      Amatantadine Was Not Effective In This Small Study of
      Receiving Interferon Without Ribivarin
      (Tueber, abstract 778)

      55 previous IFN non-responders with chronic HCV
      received IFN 6 MU tiw
      for 24
      weeks followed by 3 MU for an additional 24 weeks.
      Amantadine sulfate
      or a matched placebo (n=29) was given orally twice
      daily for 48 weeks.
      Because of an initial low response rate at week 12
      (13/55 patients) and
      high breakthrough rate (8/13 patients) after IFN dose
      was reduced , a
      virologic end-of-treatment response with undetectable
      HCV viral load
      copies/ml) was achieved in only 5 patients (1
      receiving IFN+amantadine,
      and 4
      receiving IFN+placebo). After 24 weeks follow-up a
      sustained virologic
      response was observed in only 2 patients receiving IFN
      and placebo.
      and quality of life analysis revealed a substantial
      improvement of the
      Profile of Mood States scale (POMS) concerning the
      parameters fatigue
      (p<0.05) and vigor (p<0.05) in patients receiving
      compared to patients receiving IFN alone. But since
      RBV was not used
      health & quality of life results appear tentative to
      me. Authors
      IFN+amantadine combination was well tolerated without
      any serious
      events. The author concluded IFN+amantadine does not
      increase low
      virologic response rate of IFN therapy in
      non-responders, but it may
      lead to
      improved health-related quality of life.

      Long-Term Response to Interferon+Amantadine is
      Significantly Higher
      Than to
      Interferon Alone in Chronic HCV Treatment Na�ve
      (Mangia, abstract 636)

      This multi-center controlled study of 194 patients
      compared the
      efficacy of IFN monotherapy to IFN+amantadine in
      treatment na�ve
      with chronic HCV without cirrhosis. Patients were
      randomized to IFN 6
      MU tiw
      plus amantadine (200 mg/day), or to IFN monotherapy
      for 48 weeks
      The main end-point was sustained undetectable HCV
      viral load 6 months
      the end of treatment. The secondary study end-point
      was ALT
      normalization and
      HCV viral load at the end of treatment (ETR).

      ETR was seen in 41% in amantadine+IFN group vs 22.3%
      in IFN group
      Relapse rates were about the same (26.8% vs 28.5%).
      Sustained virologic
      response was 30% in amantadine group and 16% in IFN
      alone group

      Daily Induction 18 MU Interferon + Ribivarin +
      Amantadine in Relapsers:
      kinetics & tolerability (Weegink, abstract 1135)

      28 patients with chronic HCV who had a virologic
      relapse were retreated
      IFN alfa-2a 6 MU every 8 hours for 2 weeks in
      combination with
      1000-1200 mg/day and amantadine 100 mg per day (8
      genotype 1 and 20
      had genotype non-1). This study explored HCV viral
      kinetics and adverse
      events. 5 patients had previously been treated with
      treatment and after 1 and 2 weeks after the start of
      treatment viral
      load was
      monitored using the qualitative Roche HCV 2.0 Assay
      (lower limit of
      50 IU/ml), and by the quantitative Roche Monitor
      version 2.0 assay
      limit of detection 600 IU/ml).

      All 28 patients completed the 2 week high dose
      induction treatment.
      Tiredness, flu-like symptoms, sleeping disorders,
      ittitability, and
      loss of
      appetitie were the most common side effects, occurring
      in almost all
      patients. Authors reported, however, that the severity
      of the side
      were similar to those occurring during initial
      treatment with 3-6 MU
      OFN tiw.
      At week 1 7/28 and at week 2 14/28 had undetectable
      HCV by the
      test (<50 IU/ml). At week 1 and 2 19/28 and 25/28,
      respectively, had
      undetectable viral load using the quantitative test
      (<600 IU/ml). By
      week 1
      the viral load had declined in all patients, in 17/28
      by 3-5 logs and
      by 1-2 logs. At week 2, the qualitative PCR was
      negative in 2/8
      patients with
      genotype 1 and in 10/20 patients with genotype non-1.
      The authors
      high dose IFN induction retreatment for 2 weeks, in
      combination with
      RBV+amantadine, in chronic HCV, who had a virologic
      relapse, is well
      tolerated and is associated with a rapid decline in
      viral load. After
      weeks, 89% of patients had a viral load <600 IU/ml and
      the qualitative
      was undectable <50 IU/ml in 50% of patients. I think
      its important to
      bear in
      mind that a number of viral kinetics studies have been
      conducted using
      dose induction therapy, and it is my opinion that it
      has yet to be
      established that very early high viral load decline
      rates produces
      sustained virologic response rates.

      The previous high-dose induction study nicely
      transitions into
      study data reported using Pegasys plus amantadine.

      Pegasys In Combination with Amantadine and Various
      other Drugs ( Di
      Bisceglie, abstract 1139)

      For background purposes IFN monotherapy in untreated
      patients yields
      10 to 18% sustained virologic response rates in
      various studies, while
      Pegasys monotherapy studies have shown about a 35%
      sustained virologic
      response rate. In this study patients were randomized
      in a 3:3:1:1
      ratio as:

      Group A: IFN a-2b + RBV (n=60)
      Group B: Pegasys IFN a-2a + mycophenolate mofetil
      Group C: Pegasys IFN a-2a + amantadine (n=20)
      Group D: Pegasys IFN a-2a + amantadine + ribivarin

      Patients were stratified according to genotype 1 vs
      non-1, and viral
      load (<1
      x 106 IU/mL [low] vs >1 x 106 IU/mL [high]).
      Treatment is for 48
      weeks with
      24 weeks follow-up. Outcome was assessed as virologic
      response (HCV RNA
      IU/ml and >2 log drop from baseline using the Amplicor
      HCV test version
      or biochemical response (normalization of serum ALT)
      assessed at weeks
      4, 12,
      24, 48, 60, 68, and 72. 153 patients were enrolled and
      149 have
      completed at
      least 4 weeks of treatment, 148 patients at least 12
      weeks treatment
      and 104
      patients at least 24 weeks of treatment. 5 patients
      were discontinued
      due to
      expected adverse events, 3 patients have discontinued
      for non-safety
      and 7 dropped out after randomization without taking
      any study

      Mean age was 43-45.7 years across all 4 groups. Mean
      weight was 84 in
      A, 87 in B, 85 in C, and 90 in D. Sex was 64%/36% M/F
      in A, and about
      same in B & C, and was 79%/21% in D. Mean ALT was 97
      in A, 117, B, 120
      in C,
      and 107 in D. Viral load (low/high) was 33%/67% in A,
      36%/63% in B,
      in C, and 36%/63% in D. HCV genotype was relatively
      similar across all
      (70%-76% genotype 1, 24%-27% non-1).

      Week 24: HCV-RNA <50 IU/ml & ALT & >2 Log Drop

      HCV-RNA Normal ALT >2 log drop
      A 21/37 56% 27/37 73% 23/37 62%
      B 21/41 51% 21/39 54% 28/40 70%
      C 9/13 69% 7/13 54% 12/13 92%
      D 8/13 61% 9/13 69% 11/13 84%

      Roche researchers concluded that these early findings
      over weeks 4, 12
      and 24
      show a trend to similar or greater benefit using the
      new therapies
      to current standard of care, and similar safety
      profile was displayed
      all treatment arms. Additionally, they concluded these
      early findings
      show new therapies revealing greater response rates or
      for those who
      tolerate standard IFN+RBV therapy. These results
      support continuing the
      present study and starting larger phase III studies to
      test antiviral

      Amantadine Plus IFN+RBV in Previous Non-Responders
      (Younossi, abstract 1140)

      This open-label pilot study treated 20 previous
      non-responders with
      IFN+RBV+amanatadine. Patients had previous treatment
      with IFN
      followed by combination IFN (Intron A 3 MU) tiw +
      ribivarin 800 mg/day
      (n=10), or Intron A 3 Mu tiw + amantadine 200 mg/day
      (n=10). One month
      following discontinuation of these regimens patients
      received Intron A
      3 MU +
      RBV 1000-1200 mg/day + amantadine 200 mg /day. ALT,
      HCV-RNA by PCR, and
      Health Related Quality of Life (CLDQ and SF-36) were
      evaluated. For
      with a undetectable HCV viral load at the end of 24
      weeks of therapy, a
      complete 48 week course of triple therapy was given.
      The analysis is
      as intent-to-treat.

      60% of patients were male, age was 43�5, 85% white,
      85% genotype 1, 20%
      histologic cirrhosis, baseline viral load 1.85 million
      � 1.28 million
      copies/ml and baseline ALT was 130 � 100.

      Of the 20 patients enrolled, 4 (20%) discontinued due
      to side effects
      but 15
      have completed the regimen. 12, 24 and 48 week viral
      (undetectable HCV viral load by PCR) was achieved by 6
      (30%), 5 (25%),
      and 3
      (15%) of the patients, respectively. The last patient
      is on week 35 of
      regimen with undetectable HCV RNA. Of 3 patients with
      negativity, 2 have follow-up HCV-RNA and both remain
      negative (median
      follow-up is 6 weeks). Study authors report that this
      early viral
      was equally divided among those previously treated
      with IFN+RBV or
      IFN/amantadine. The authors concluded that in this
      group of previous
      non-responders, triple amantadine therapy was
      associated with
      early viral undetectability, and durability is being

      Do You Yahoo!?
      Get email alerts & NEW webcam video instant messaging with Yahoo! Messenger
    Your message has been successfully submitted and would be delivered to recipients shortly.