Randomized, placebo-controlled, double-blind trial with interferon-[alpha] with and without amantadine sulphate in primary interferon-[alpha] nonresponders with chronic hepatitis C.
Teuber, G. 1; Berg, T. 2; Naumann, U. 2; Raedle, J. 1; Brinkmann, S. 3; Hopf, U. 2; Zeuzem, S. 1
[Article]
Journal of Viral Hepatitis.
8(4):276-283, July 2001.
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In primary interferon-[alpha] (IFN-[alpha]) nonresponders with chronic hepatitis C, retreatment with IFN-[alpha] has only limited efficacy with sustained response rates below 10%. Therefore, the aims of the present study were to compare the efficacy and safety of IFN-[alpha] alone or in combination with amantadine sulphate in nonresponders to previous IFN-[alpha] monotherapy. Fifty-five IFN-[alpha] nonresponders with chronic hepatitis C (mean age: 46.6 years) received IFN-[alpha] 6 MIU thrice weekly for 24 weeks followed by 3 MIU thrice weekly for additional 24 weeks. Amantadine sulphate (n =26) or a matched placebo (n =29) was given orally twice daily for 48 weeks. Because of a low initial response rate at week 12 (13/55 patients) and a high breakthrough rate (8/13 patients) after IFN-[alpha] dose reduction in week 24, a virological end-of-treatment response with undetectable serum HCV-RNA (< 1000 copies/mL) was achieved in only five patients (IFN-[alpha]/amantadine sulphate, one patient; IFN-[alpha]/placebo, four patients). After 24 weeks follow-up a sustained virological response was observed in only two patients receiving IFN-[alpha] and placebo. Health-related quality-of-life analysis showed a substantial improvement of the Profile of Mood States (POMS) scale concerning the subscales fatigue (P < 0.05) and vigor (P < 0.05) in patients receiving combined IFN-[alpha]/amantadine sulphate treatment compared with those treated with IFN-[alpha] alone. IFN-[alpha]/amantadine sulphate combination therapy was well tolerated without any serious adverse events. In conclusion, retreatment with IFN-[alpha] and amantadine sulphate does not increase the low sustained virological response rates of IFN-[alpha] therapy in primary IFN-[alpha] nonresponders with chronic hepatitis C, but may lead to a sustained improvement of health-related quality-of-life.
(C) 2001 Blackwell Science Ltd.