Therapy of hepatitis C: interferon alfa-n1 trials.

Interferon alfa-n1 is produced from a lymphoid cell line and consists of multiple alpha interferon subtypes. Early studies indicated that interferon alfa-n1 was effective against hepatitis C, and a meta-analysis of published trials indicated that it was equally likely as recombinant alpha interferons to produce an end-of-treatment biochemical and histological response. However, there appeared to be a lower rate of posttreatment relapse after a 6-month course of interferon alfa-n1, so that the sustained response rate was 25% compared with 16% for recombinant alpha interferons. Subsequently, the efficacy of interferon alfa-n1 has been compared with recombinant alpha interferon directly in two large multicenter studies. The 096 International Hepatitis Comparative Study compared alfa-n1 with interferon alfa-2b in doses of 3 million units (MU) three times weekly for 24 weeks in a total of 1,071 patients. Biochemical end-of-treatment response rates were similar (35% for alfa-n1; 38% for alfa-2b), as were virological and histological responses. Relapse occurred more frequently after interferon alfa-2b, so that sustained biochemical (10.3% vs. 6.7%) and virological responses at 12 months were higher for alfa-n1. In a second study from Italy, interferon alfa-n1 was compared with interferon alfa-2a, using higher doses (6 MU three times weekly) until a biochemical response was obtained, and then using 3 MU three times weekly for a total of 12 months. The combined biochemical and virological sustained response rates were higher than reported with 6 months of treatment and were similar for alfa-n1 (17%) as for alfa-2a (16%). The superiority of 12 versus 6 months of treatment was also confirmed in the large multicenter 091 European Comparative Treatment Schedules study of 440 patients given four different regimens of therapy. Sustained biochemical response rates were 6% in patients who received 3 MU three times weekly for 6 months and 19% in those who received this dose for 12 months. When given for 12 months, there was no advantage to a slightly higher dose of interferon alfa-n1 (5 MU three times weekly). Thus, therapy with interferon alfa-n1 produces sustained response rates equivalent to the best obtained with recombinant alpha interferon. The optimal treatment regimen appears to be 3 MU given three times weekly for 12 months.