RANDOMIZED 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

Background Only 15-20% of patients with chronic hepatitis C achieve a sustained virological response with interferon therapy. The aim of thi s study was to compare the efficacy and safety of interferon alpha 2b in combination with oral ribavirin with interferon alone, for treatmen t of chronic infection with hepatitis C virus (HCV). Methods 832 patie nts aged 18 years or more with chronic HCV who had not been treated wi th interferon or ribavirin, were enrolled and randomly allocated one o f three regimens: 3 mega units (MU) interferon alpha 2b three times a week plus 1000-1200 mg ribavirin per day for 48 weeks; 3 MU interferon alpha 2b three times a week plus 1000-1200 mg ribavirin per day for 2 4 weeks; or 3 MU interferon alpha 2b three times a week and placebo fo r 48 weeks. All patients were assessed for safety, tolerance, and effi cacy at the end of weeks 1, 2, 4, 6, and 8, and every 4 weeks during t reatment. After treatment was completed patients were followed up on w eeks 4, 8, 12, and 24. The primary endpoint was loss of detectable HCV -RNA (serum HCV-RNA <100 copies/mL) at week 24 after treatment.Finding s Sustained virological response at 24 weeks after treatment, was foun d in 119 (43%) of the 277 patients treated for 48 weeks with the combi nation regimen, 97 (35%) of the 277 patients treated for 24 weeks with the combination regimen (p=0.055), and 53 (19%) of the 278 patients t reated for 48 weeks with interferon alone (p<0.001 vs both combination regimens, intention-to-treat analysis). Logistic regression identifie d five independent factors significantly associated with response: gen otype 2 or 3, viral load less than 2 million copies/mL, age 40 years o r less, minimal fibrosis stage, and female sex. Among patients with fe wer than three of these factors the odds ratio of sustained response w as 2.6 (95% CI 1.4-4.8; p=0.002) for the 48 week combination regimen c ompared with 24 weeks of the combination regimen. Discontinuation of t herapy for adverse events was more frequent with combination (19%) and monotherapy (13%) given for 48 weeks than combination therapy given f or 24 weeks (8%). Interpretation An interferon alpha 2b plus ribavirin combination is more effective than 48 weeks of interferon alpha 2b mo notherapy and has an acceptable safety profile. Patients with few favo urable factors benefit more from extending the duration of combination therapy to 48 weeks.