Randomized, controlled trial with IFN-α combined with ribavirin with and without amantadine sulphate in non-responders with chronic hepatitis C

• Published in: Journal of hepatology Vol. 39; no. 4; pp. 606 - 613
• Main Authors: Teuber, Gerlinde, Pascu, M, Berg, T, Lafrenz, M, Pausch, J, Kullmann, F, Ramadori, G, Arnold, R, Weidenbach, H, Musch, E, Junge, U, Wiedmann, K.H, Herrmann, E, Zankel, M, Zeuzem, S
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.10.2003; Elsevier
• Subjects: Adult; Aged; Amantadine; Amantadine - administration & dosage; Amantadine - adverse effects; Amantadine - therapeutic use; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Antiviral retreatment; Biological and medical sciences; Chronic hepatitis C; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Hepacivirus - drug effects; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Human viral diseases; Humans; Infectious diseases; Interferon; Interferon alpha-2; Interferon-alpha - administration & dosage; Interferon-alpha - adverse effects; Interferon-alpha - therapeutic use; Male; Medical sciences; Middle Aged; Non-responders; Recombinant Proteins; Ribavirin; Ribavirin - administration & dosage; Ribavirin - adverse effects; Ribavirin - therapeutic use; Treatment Outcome; Viral diseases; Viral hepatitis; Antiviral retreatment; Amantadine; Interferon; Chronic hepatitis C; Non-responders; Ribavirin; Agonist; Alpha interferon; Hepatic disease; Glutamate receptor; Randomization; Immunotherapy; Antiviral; Clinical trial; Antagonist; Viral hepatitis C; Human; Drug combination; Treatment resistance; Dopamine receptor; Cytokine; Antiparkinson agent; Biological activity; Infection; Chemotherapy; Chronic; Viral disease; Dopamine agonist; Digestive diseases; Nucleosidic analog; NMDA receptor
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(03)00298-8

Background/Aims: Efficacy and safety of interferon-α (IFN-α)/ribavirin retreatment with or without amantadine sulphate were evaluated in non-responders with chronic hepatitis C. Methods: Two hundred twenty five consecutive non-responders to previous antiviral treatment(s) with IFN-α alone or in combination with ribavirin or amantadine were treated with IFN-α 2b 5 MU daily for 4 weeks, 5 MU tiw for 20 weeks, followed by 3 MU tiw for additional 24 weeks combined with ribavirin 1000–1200 mg/d. One hundred fifteen of 225 patients were randomized to receive amantadine sulphate 100 mg bid for 48 weeks. Treatment was discontinued in patients with detectable serum hepatitis C virus (HCV)-RNA at treatment week 24. Results: An overall sustained virologic response with undectable serum HCV-RNA levels was observed in 49/225 patients (22%). Patients infected with HCV-genotype non-1 ( P<0.001), low viremia ( P=0.011) and only one previous antiviral treatment ( P=0.032) were more likely to respond to antiviral retreatment. There was a trend towards higher sustained virologic response rates in patients receiving triple retreatment compared with those treated with IFN-α/ribavirin alone (25 versus 18%, P=0.172). Conclusions: The addition of amantadine was well tolerated and led to an improvement of sustained virologic responses compared with retreatment with IFN-α/ribavirin alone, in particular in patients with low baseline viremia.