Amantadine triple therapy for non-responder hepatitis C patients. Clues for controversies (ANRS HC 03 BITRI)

• Published in: Journal of hepatology 2006-03, Vol.44 (3), p.484-490
• Main Authors: Maynard, Marianne, Pradat, Pierre, Bailly, François, Rozier, Frédéric, Nemoz, Chantal, Si Ahmed, Si Nafa, Adeleine, Patrice, Trépo, Christian, a French Multicenter Group, and
• Format: Article
• Language: English
• Subjects: Adult; Aged; Amantadine; Amantadine - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - therapeutic use; Biological and medical sciences; Biopsy; Clinical trial; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Gastroenterology. Liver. Pancreas. Abdomen; Hepacivirus - drug effects; Hepacivirus - genetics; Hepatitis C; Hepatitis C - drug therapy; Hepatitis C - pathology; Hepatitis C - virology; Human viral diseases; Humans; Infectious diseases; Interferon-alpha - therapeutic use; Life Sciences; Male; Medical sciences; Middle Aged; Other; Pharmacology. Drug treatments; Polyethylene Glycols; Prospective Studies; Recombinant Proteins; Ribavirin - therapeutic use; RNA, Viral - genetics; Treatment; Treatment Outcome; Triple therapy; Viral diseases; Viral hepatitis
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2005.11.038

To determine whether addition of amantadine to pegylated interferon/ribavirin improved response rates among chronic hepatitis C patients, non-responders to interferon/ribavirin and study the dynamic of response. In a double blind, multicenter, randomized trial, 200 non-responder patients received pegylated interferon 1.5 μg/kg per week and ribavirin 800–1200 mg/day, plus either amantadine 200 mg/day or placebo for 48 weeks. Endpoints were virological responses, ALT normalization, and histological benefit overtime. Twenty percent of all patients achieved a sustained virological response (SVR). This rate was 8% higher in the triple therapy group (24%) compared with the double therapy group (16%) ( P=0.22). A better virological response rate at week 24 was observed in the triple regimen group (43 vs 29%; P=0.06), which was lost at week 48 suggesting viral escape. The biochemical response rate was also significantly higher with triple therapy at week 12 (63 vs 49%; P=0.05) and week 24 (64 vs 49%; P=0.03). Fibrosis stabilized or improved in 77% of all patients. Re-treatment of interferon/ribavirin non-responder patients should be encouraged since a substantial proportion benefits from re-treatment with pegylated interferon/ribavirin ± amantadine. In triple therapy involving amantadine, a time wise response and an increased SVR rate in subgroups less prone to viral breakthrough suggest clues for existing controversies.