Safety of combination interferon alfa-2b/ribavirin therapy in chronic hepatitis C-relapsed and treatment-naive patients.

ABSTRACT

The coadministration of ribavirin with recombinant interferon alfa-2b (rIFN-alpha 2b) compared with rIFN-alpha 2b alone markedly enhanced sustained virologic response rates in relapsed and treatment-naive chronic hepatitis C patients. The potential for ribavirin to likewise exacerbate the adverse events associated with the alpha interferons is reviewed. The overall safety and tolerability of combination rIFN-alpha 2b/ribavirin therapy was evaluated in 2,089 patients treated in phase III clinical studies conducted in the United States and internationally. Serious adverse events were also evaluated on an interim basis in > 25,000 patients--a majority of whom were treated with combination therapy (open label)--treated worldwide in investigator-initiated studies. Patients in the phase III studies received 3 million International Units rIFN-alpha 2b three times per week by subcutaneous injection plus either ribavirin or placebo orally in divided daily doses of 1,000 or 1,200 mg for patients weighing < or = 75 or > 75 kg, respectively. Adverse event frequency and severity and dose modifications were recorded throughout the 24-week (relapse) or 48-week (naive) treatment period and 24-week follow-up period. Clinically significant adverse events included anemia and depression. There was no evidence that the adverse effects of alpha interferon (e.g., fatigue, depression, neutropenia) were exacerbated by ribavirin. Severe adverse events were limited due to strict adherence to dose-modification criteria; approximately 6% to 9% of patients discontinued combination therapy because of an adverse event. Clinically serious adverse events, dose reductions and discontinuations, and potential mechanisms of toxicity associated with rIFN-alpha 2b and ribavirin are examined.