Pilot dose-finding trial on interferon alpha in combination with ribavirin for the treatment of chronic hepatitis C in patients not responding to interferon alone.

ABSTRACT

BACKGROUND: Effectiveness of combination therapy with standard interferon alpha doses and ribavirin is far from being demonstrated in patients with hepatitis C non responders to interferon alpha monotherapy. Recent kinetic studies revealed that these doses may be suboptimal. AIMS: To find the criteria for optimisation of the interferon dose, to be used in combination with ribavirin in patients with hepatitis C non responders to interferon alpha monotherapy. PATIENTS Sixty-three patients enrolled in a pilot controlled trial were treated for 6 months with ribavirin ([1000-1200 mg daily) and were randomised to concurrently receive interferon alpha 2b for 6 months at 3 Million Units thrice weekly [group A (21 patients)], 5 MU thrice weekly [group B (21 patients)] and 5 million units daily [group C (21 patients)]. RESULTS: A sustained virological response was observed in 1 patient from group A (5%), 2 patients from group B (9%) and 8 patients from group C (38%; p=0.02 vs group A; p=0.03 vs group B). Side-effects were not significantly different between the 3 groups. Multivariate analysis showed that infection by hepatitis C virus genotypes 2 or 3 and interferon alpha dosage of 5 million units daily were independent predictors of sustained response. CONCLUSIONS: These results suggest that higher interferon doses administered daily in combination with ribavirin could be more effective in those patients with hepatitis C who had not responded to interferon alone.