RESPONSE TO HIGHER DOSES OF INTERFERON ALFA-2B IN PATIENTS WITH CHRONIC HEPATITIS-C - A RANDOMIZED MULTICENTER TRIAL

To evaluate response rates to 3, 5, or 10 million units (MU) of interf eron alfa-ab, given thrice weekly, and to determine whether higher dos es of interferon increase the likelihood or durability of the response , a multicenter, randomized trial was performed at nine academic medic al centers in the United States, Two hundred forty eight patients with chronic hepatitis C were randomized to receive 3, 5, or 10 MU of inte rferon alfa-ab thrice weekly for 12 weeks. Based on the alanine aminot ransferase (ALT) response at treatment-week 12, the patients were rera ndomized to additional therapy at the same or at increased doses for a n additional 12 to 36 weeks; in the case of no response to the highest dose, the patients were discontinued from the study, Serum ALT concen trations and liver histology were measured. The overall complete respo nse rates to 3, 5, or 10 MU were not different at treatment-week 12 (3 1% vs, 42% vs, 40%, not significant), The majority of week-12 responde rs continued to respond during additional treatment. When the treatmen t was discontinued, 15.4% to 19.0% of patients maintained their respon se, Of the nonresponders to 3 MU at week 12, who were continued on 3 M U for an additional 12 weeks, none responded, However, response to add itional therapy occurred in 12% of week-12 nonresponders, whose dose w as escalated from 3 or 5 MU to 10 MU. The only baseline features assoc iated with the treatment response were the absence of fibrosis or cirr hosis on the pretreatment Liver biopsy and viral genotype, We conclude that the initial response to interferon in patients with chronic hepa titis C is not increased by treatment with higher doses of the drug, P atients who do not respond to 3 MU by treatment-week 12 will not respo nd with continued therapy at that dose; however, a proportion of patie nts who do not respond to 12 weeks of treatment with 3 or 5 MU may res pond to higher doses, Although the long-term sustained response rates are marginally increased with interferon doses above 3 MU three times per week, the side effects are difficult to tolerate. The analysis of baseline factors in relation to response identified no single baseline factor associated with a low-enough response rate to warrant withhold ing interferon therapy from patients with chronic hepatitis C.