Pilot study of interferon-α high-dose induction therapy in combination with ribavirin plus amantadine for nonresponder patients with chronic hepatitis C

Summary

Ribavirin plus interferon-α (IFNα) combination has led to a marked advance in the treatment of IFNα-naive or relapser patients with chronic hepatitis C but was shown to be only marginally effective in IFNα-nonresponders. We therefore conducted a pilot study to see whether an intensified treatment protocol might be more effective in inducing a virological response in patients who had not responded virologically to previous IFNα monotherapy. 14 nonresponder patients with histologically proven chronic hepatitis C were included in the study. Patients received 9 MU IFNα-2a daily for one week followed by 9 MU IFNα every second day for further 5 weeks. With the beginning of the seventh week, patients were treated with 6 MU IFNα thrice in week (tiw) for a period of 6 weeks (until week 12). IFNα was continued up to 48 weeks at a dose of 3 MU IFNα tiw. Ribavirin (1000-1200 mg/day) and amantadine sulphate (200 mg/day) was given orally for 48 weeks. One patient discontinued therapy after first IFNα injection and one other patient after 12 weeks of therapy because of side effects. The remaining 12 patients completed treatment according to the protocol. An initial virological response at week 24 was achieved in 2 of the 14 patients (14 %) and both patients remained HCV RNA negative at the end of treatment. However, both patients relapsed 4 weeks after completion of therapy, and therefore none of the patients achieved a virological sustained response. Viral dynamics studies showed a marked decline in hepatitis C viremia during the first 6 weeks of high-dose IFNα. After IFNα dose reduction, however, viremia stabilized or increased in most patients. These data indicate, that even triple therapy with high-dose IFNα plus ribavirin and amantadine fails to improve significantly the response rates in IFNα-nonresponders.

Interferon-α-Hochdosis-Induktionstherapie in Kombination mit Ribavirin plus Amantadin bei Nonresponderpatienten mit chronischer Hepatitis C: Ergebnisse einer Pilotstudie

Die Kombinatonstherapie aus Interferon-α (IFNα) plus Ribavirin hat zu einer deutlichen Verbesserung der Ansprechraten bei unvorbehandelten bzw. Relapsepatienten mit chronischer Hepatitis C geführt, war jedoch nur marginal wirksam bei IFNα-Nonrespondern. In der vorliegenden Pilotstudie sind wir der Frage nachgegangen, ob durch eine intensivierte antivirale Therapie eine Verbesserung der Responseraten bei virologischen Nonrespondern erzielt werden kann. 14 Nonresponderpatienten mit histologisch gesicherter chronischer Hepatitis C wurden in die Studie eingeschlossen. Die Patienten erhielten 9 Mio. Einh. IFNα-2a täglich für 7 Tage gefolgt von 9 Mio. Einh. IFNα alle 2 Tage für 5 Wochen. Anschließend (Woche 7-12) wurden die Patienten mit 3 × 6 Mio. Einh. IFNα/Woche gefolgt von 3 × 3 Mio. Einh./Woche (Woche 13-48) behandelt. Zusätzlich erhielten alle Patienten Ribavirin (1000-1200 mg/Tag) und Amantadinsulfat (200 mg/Tag) für 48 Wochen. Ein Patient beendete die Therapie nach der ersten IFNα-Injektion und ein weiterer nach der 12. Therapiewoche aufgrund von Nebenwirkungen. Die übrigen 12 Patienten führten die Therapie protokollgemäß durch. Eine initiale virologische Response zur Woche 24 wurde nur bei 2 der 14 Patienten (14 %) erreicht, und beide Patienten erlitten 4 Wochen nach Therapieende einen Relapse. Untersuchungen zur Dynamik der Hepatitis-C-Virämie zeigten eine signifikante Reduktion der Virusreplikation während der ersten 6 Induktionstherapiewochen. Nach IFNα-Dosisreduktion zeigten allerdings die meisten Patienten eine Stabilisierung bzw. einen Anstieg der Virämie. Unsere Daten zeigen, dass eine antivirale Tripeltherapie mit Hochdosis-IFNα plus Ribavirin und Amantadin nicht in der Lage ist, die dauerhaften Responseraten bei IFNα- Nonrespondern mit ungünstigen Responsefaktoren zu verbessern.

Hepatitis C Virus Kinetics - High-Dose Interferon-α - Triple Therapy - Amantadine - Ribavirin

Hepatitis-C-Virus-Kinetik - Hochdosis-Interferon-α - Tripeltherapie - Amantadin - Ribavirin

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