Randomized, placebo‐controlled, double‐blind trial with interferon‐α with and without amantadine sulphate in primary interferon‐α nonresponders with chronic hepatitis C

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Abstract
In primary interferon‐α (IFN‐α) nonresponders with chronic hepatitis C, retreatment with IFN‐α 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‐α alone or in combination with amantadine sulphate in nonresponders to previous IFN‐α monotherapy. Fifty‐five IFN‐α nonresponders with chronic hepatitis C (mean age: 46.6 years) received IFN‐α 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‐α 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‐α/amantadine sulphate, one patient; IFN‐α/placebo, four patients). After 24 weeks follow‐up a sustained virological response was observed in only two patients receiving IFN‐α 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‐α/amantadine sulphate treatment compared with those treated with IFN‐α alone. IFN‐α/amantadine sulphate combination therapy was well tolerated without any serious adverse events. In conclusion, retreatment with IFN‐α and amantadine sulphate does not increase the low sustained virological response rates of IFN‐α therapy in primary IFN‐α nonresponders with chronic hepatitis C, but may lead to a sustained improvement of health‐related quality‐of‐life.