IFN Alfa-2b Plus Ribavirin Combination Increases Sustained Response Rate
Professor Thierry Poynard (Paris, France) reviewed results of meta-analyses of randomized trials designed to evaluate the benefit of higher doses or longer duration of IFN alfa compared with the traditional IFN alfa regimen (3 MU TIW x 6 months) (Hepatology. 1996;24:778-789) and to evaluate the efficacy of ribavirin in combination with IFN alfa-2b for the treatment of chronic Hepatitis C. Four randomized controlled trials were identified evaluating the efficacy of ribavirin and IFN alfa-2b in combination in 189 previously untreated patients infected with HCV. The results of the meta-analysis indicate that there was a significantly (P<.001) greater efficacy in terms of sustained ALT response (44%) for the combination compared with IFN alfa-2b monotherapy (18%). The ALT relapse rate also was lower for patients receiving combination therapy compared with those receiving IFN alfa-2b monotherapy (24% vs 38%). In terms of HCV RNA negativization, 41% versus 16% of patients receiving IFN alfa-2b plus ribavirin and IFN alfa-2b single-agent therapy, respectively, demonstrated sustained HCV RNA negativization 6 months after the end of treatment (P<.001). These findings indicate that treatment with IFN alfa 3 MU TIW plus ribavirin results in an increased sustained biochemical and virologic response rate and decreased relapse rate compared with IFN alfa monotherapy. Other ongoing, large randomized clinical trials will provide additional clinical data.
IFN alfa-2b plus ribavirin produces higher sustained response rates than IFN monotherapy.
A clinical study of the combination was presented as a poster by Khakoo et al (London, United Kingdom). In this trial, 36 anti-HCV positive, serum HCV RNA – positive patients were randomized to receive IFN alfa-2b 3 MU TIW, ribavirin 1 or 1.2 g/day, or the combination of IFN alfa-2b and ribavirin using the same doses as in the monotherapy arms. Patients were treated for 4 weeks and followed for an additional 6 weeks. At the end of treatment, ALT had returned to normal in 7/12 patients receiving IFN alfa-2b, 6/12 patients receiving ribavirin, and 9/12 patients receiving the combination. Seven of 12 patients in the IFN group, 0/12 patients in the ribavirin group, and 10/12 patients in the combination group had a > 1 log 10 decline in serum HCV RNA level (P <.05 vs IFN alfa-2b monotherapy; P<.01 vs ribavirin monotherapy). Figure 2 shows the mean decline in serum RNA titers for the three treatment arms over the 10-week study period. These data indicate that combination therapy produces a more rapid decline in serum HCV RNA levels, suggesting that the higher sustained response rates may result from an improvement in initial response as well as a reduction in the relapse rate.
Khakoo SI, Wells B, Glue P, Bell A, Dash C, Dusheiko GM. Comparison of reduction of serum Hepatitis C levels with interferon alpha alone or in combination with ribavirn. J Hepatol. 1997;26(suppl 1):84. Abstract P/C01/32.