Comparative study of the efficacy of an induction dose of interferon-alpha2b with ribavirin compared with standard combined treatment in naive patients with chronic hepatitis C.

The efficacy and secondary effects of an induction dose of interferon-alpha2b (IFN-alpha2b) with ribavirin compared with standard combined treatment in naive patients with chronic hepatitis C infection were compared. A prospective study was undertaken between March 1998 and November 2001 in which 84 Spanish hospitals took part. Six hundred and fourteen naive patients (age range 18-65 years) diagnosed with chronic hepatitis C virus (HCV) infection and without cirrhosis or co-infection by other viruses, were included. Patients were divided into two groups. Group A (n = 304) received induction treatment with a daily dose of 5 MU of IFN-alpha2b for 4 weeks, followed by 5 MU three times a week with ribavirin (1000-1200 mg/day, according to weight) until completing 1 year of treatment. Group B (n = 310) received the standard dose of IFN-alpha2b of 3 MU three times per week for 48 weeks together with ribavirin (1000-1200 mg/day, according to weight). Both groups were completely comparable according to age, gender, body weight, transaminase levels, genotype, viral load and hepatic inflammatory activity (Knodell Index). No control group was included for ethical reasons. Pegylated interferon was not available at the time of the study. Serum baseline samples were collected for the determination of genotype. Samples were also collected at baseline, weeks 4, 12, 24, 48 and 72, in order to detect and quantify HCV-RNA. The efficacy of treatment was evaluated by means of sustained viral response (SVR) characterized by persistent negativity of HCV-RNA at the end of the follow-up period. At week 4, the response to treatment was greater in group A (49.6%) compared with group B (34.5%) (P = 0.0002), and was maintained until week 12 (64.1% compared with 55.8% respectively) (P = 0.03). These differences disappeared at week 24, when group A (69%) was compared with group B (65%) (NS). At week 48, the response rate for group A was 50.6% compared with group B 47.4% (NS), and at week 72, the SVR in group A was 46% compared with 40.3% for group B (NS). The global SVR was 43.1%. On analysing the response to treatment according to genotype and viral load, we found that the induction treatment was slightly superior in patients with genotype 1 and an elevated viral load (>2 x 10(6) copies/ml). They achieved a SVR in group A of 39.1% compared with 25.5% in group B (P < 0.05). However, this slight improvement obtained in group A, was achieved at the expense of a greater percentage of dropouts compared with group B (6.4% vs 2.2%, P < 0.01); a greater rate of side effects (58.5 vs 36.7%, P < 0.05) and also a greater percentage of neutropenia (3.1% vs 0.9%, P < 0.05). The induction treatment presented a better initial response, but this was not maintained at the end of treatment, and did not improve the results obtained with the standard treatment. Although the patients with genotype 1 and elevated viral load had a better response with the induction treatment, this was accompanied by a greater percentage of dropouts and secondary effects. It would be interesting to repeat this type of study in the future, using pegylated interferon.

RCT Entities:   Population Interventions Outcomes