Randomised trial of interferon alpha;2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha;2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus

摘要

Background:Only 15ndash;20percnt; of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of this study was to compare the efficacy and safety of interferon alpha;2b in combination with oral ribavirin with interferon alone, for treatment of chronic infection with hepatitis C virus (HCV).Methods:832 patients aged 18 years or more with chronic HCV who had not been treated with interferon or ribavirin, were enrolled and randomly allocated one of three regimens: 3 mega units (MU) interferon alpha;2b three times a week plus 1000ndash;1200 mg ribavirin per day for 48 weeks; 3 MU interferon alpha;2b three times a week plus 1000ndash;1200 mg ribavirin per day for 24 weeks; or 3 MU interferon alpha;2b three times a week and placebo for 48 weeks. All patients were assessed for safety, tolerance, and efficacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during treatment. After treatment was completed patients were followed up on weeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCVast;RNA (serum HCVast;RNA 100 copies/mL) at week 24 after treatment.Findings:Sustained virological response at 24 weeks after treatment, was found in 119 (43percnt;) of the 277 patients treated for 48 weeks with the combination regimen, 97 (35percnt;) of the 277 patients treated for 24 weeks with the combination regimen (p 0.055), and 53 (19percnt;) of the 278 patients treated for 48 weeks with interferon alone (p 0.001 vs both combination regimens, intention to treat analysis). Logistic regression identified five independent factors significantly associated with response: genotype 2 or 3, viral load less than 2 million copies/mL, age 40 years of less, minimal fibrosis stage, and female sex. Among patients with fewer than three of these factors the odds ratio of sustained response was 2.6 (95percnt; CI; 1.4ndash;4.8; p = 0.002) for the 48 week combination regimen compared with 24 weeks of the combination regimen. Disoon-tinuation of therapy for adverse events was more frequent with combination (19percnt;) and monotherapy (13percnt;) given for 48 weeks than combination therapy given for 24 weeks (8percnt;).Interpretation:An interferon alpha;2b plus ribavirin combination is more effective than 48 weeks of interferon alpha;2b monotherapy and has an acceptable safety profile. Patients with few favourable factors benefit more from extending the duration of combination therapy to 48 weeks.