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

• Published in: Digestive and liver disease 2001-03, Vol.33 (2), p.163-172
• Main Authors: Puoti, M., Cadeo, G.P., Putzolu, V., Forleo, M.A., Barni, M.C., Cristini, G., Rossi, S., Spinetti, A., Zaltron, S., Zanini, B., Quiros-Roldan, E., Paraninfo, G., Gargiulo, F., Carosi, G.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Analysis of Variance; Antiviral Agents - administration & dosage; Biopsy, Needle; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Hepatitis C Virus; Hepatitis C Virus kinetics; Hepatitis C Virus-RNA; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - pathology; Humans; Interferon-alpha - administration & dosage; Logistic Models; Male; Middle Aged; Pilot Projects; Probability; Ribavirin - administration & dosage; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome
• ISSN: 1590-8658; 1878-3562
• DOI: 10.1016/S1590-8658(01)80073-6

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.