Twenty-four vs. forty-eight weeks of re-therapy with interferon alpha 2b and ribavirin in interferon alpha monotherapy relapsers with chronic hepatitis C.

OBJECTIVE

Roughly 50% of patients with chronic hepatitis C, who relapsed after a previous monotherapy with interferon alpha, will respond in a sustained fashion to 24 weeks of re-therapy with the combination of interferon alpha plus ribavirin. Whether prolonging treatment duration to 48 weeks will further increase sustained response rates remains ill defined. In this randomised controlled pilot trial we compared the efficacy and tolerability of a 24 week with that of a 48 week course of combination therapy with interferon alpha and ribavirin in interferon monotherapy relapsers with chronic hepatitis C.

METHODS

Interferon alpha monotherapy relapsers with chronic hepatitis C were randomised to receive interferon alpha 2b (3 x 3 MIU sc weekly) and oral ribavirin (1000/1200 mg po daily) for either 24 weeks or 48 weeks. Virological response was evaluated by HCV RNA PCR at week 10 (initial response), at the end of treatment (end of- treatment response) and at the end of 24 weeks follow-up (sustained response). Only patients with negative HCV RNA at week 10 continued treatment. Adverse events were recorded at regular intervals.

RESULTS

Thirty-seven patients were enrolled, 19 (6 females, median age 43) in the 24 week and 18 (5 females, median age 40) in the 48 week treatment arm. Baseline characteristics were similar in both groups. At treatment week 10, 12/19 (63%) in the 24 week group and 14/18 (78%) patients in the 48 week group had lost HCV RNA in serum (p = 0.33). All initial responders remained HCV RNA negative throughout the treatment period. Sustained response rates were 10/19 (53%) in the 24 week group and 13/18 (72%) in the 48 week group (p = 0.31). Three patients discontinued treatment early (two due to moderate adverse events, one due to non-compliance). Dose modifications were necessary in 9 patients, 4 in the 24 week and 5 in the 48 week group for anaemia, neutropenia, nausea and depression, respectively.

CONCLUSIONS

Prolonging interferon / ribavirin combination therapy in interferon alpha monotherapy relapsers with chronic hepatitis C from 24 to 48 weeks may increase sustained response rates. Larger controlled trials using pegylated interferon alpha and ribavirin in relapsers with chronic hepatitis C seem warranted.