Comparison of high initial and fixed-dose regimens of interferon-alpha2a in chronic hepatitis C: a randomized controlled trial. French Multicenter Interferon Study Group.
The efficacy of a high-dose de-escalating treatment regimen versus the standard, fixed-treatment regimen of interferon-alpha2a (IFN; Roferon-A) in chronic hepatitis C was evaluated in 291 patients who had elevated alanine aminotransferase (ALT) levels, for at least 6 months prior to the study, and histologically proven chronic hepatitis. Patients were randomized into two groups: 142 patients received IFN at a fixed dose (3 million international units (MIU) three times a week for 6 months) and 149 patients received 6 MIU three times a week for 3 months followed by 3 MIU three times a week for the next 3 months. The groups did not differ significantly with respect to age, gender or percentage of patients with cirrhosis. Response was evaluated by monitoring ALT levels monthly during treatment and during the 6 months post-treatment follow-up. Sixty-one per cent and 66% of the patients in the fixed and de-escalating treatment groups had a primary response (serum ALT normalization) during the treatment period; sustained-response rates at the end of follow-up were 20% and 29%, respectively (not significant). In non-cirrhotic patients, a primary response was recorded in 65% and 70% of the patients in the fixed and de-escalating groups; sustained-response rates were 22% and 33%, respectively. Overall, 62% of patients with a sustained response showed histological improvement. In univariate analysis, patients with sustained response tended to be non-cirrhotic and had lower initial serum gamma-glutamyl transpeptidase and ferritin levels. Multivariate analysis indicated that only ALT activity assessed at month 1 (P < 0.01) was a significant predictor of sustained response. These findings suggest that although the difference in the response rates between the de-escalating (6 MIU three times a week for 3 months; 3 MIU three times a week for 3 months) and fixed (3 MIU three times a week for 6 months) treatment regimens did not reach statistical significance, there was a clear trend towards higher response with the 6 MIU induction dose in patients without cirrhosis.
Ouzan
D
D
Institut Arnault-Tzanck, Saint-Laurent-du-Var, France.
Babany
G
G
Valla
D
D
Opolon
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001706:Biopsy; D005260:Female; D005293:Ferritins / Q000032:analysis / Q000097:blood / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism / Q000821:virology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011994:Recombinant Proteins; D005723:gamma-Glutamyltransferase / Q000032:analysis / Q000097:blood / Q000378:metabolism
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005293:Ferritins; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase