INTERFERON-ALPHA-N1 - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND THERAPEUTIC EFFICACY IN THE MANAGEMENT OF CHRONIC VIRAL-HEPATITIS

Interferon-alpha-n1 (lymphoblastoid interferon-alpha) is a nonrecombin ant 'natural' interferon derived from lymphoblastoid cells exposed to Sendai virus. In common with endogenous and recombinant interferon-alp ha molecules, interferon-alpha-n1 has antiviral, immunomodulatory and antiproliferative properties. Interferon-alpha-n1 shows some efficacy in immunocompetent adults with well-compensated chronic viral hepatiti s B. Rates of complete virological response from 5 to 79% of adults wh o received various dosage regimens of interferon-alpha-n1 in monothera py trials. Clearance of hepatitis B 'e' antigen was reported in 5 to 7 0% of patients treated with the drug. Spontaneous virological response s occurred in 0 to 48% of untreated patients. The clinical efficacy of interferon-alpha-n1 in patients with chronic hepatitis B is not impro ved by concomitantly administered deflazacort, zidovudine or levamisol e, but may be increased by a course of corticosteroid pretreatment in some patients. Interferon-alpha-n1 also shows therapeutic benefit in a dults with chronic hepatitis C. Complete biochemical responses (define d as normalisation of serum ALT levels) were achieved in 27 to 60% of adult patients treated with the drug, whereas spontaneous normalisatio n of serum ALT levels occurred in up to 11% of untreated patients. Res ponses to interferon-alpha-n1 were temporary in 27 to 78% of treatment responders but were sustained in 6 to 40% of patients. Emerging data delineating baseline factors predictive of a positive response to inte rferon-alpha-n1 treatment may aid in the selection of patients with he patitis B or C most likely to benefit from treatment with this drug. M ost patients receiving interferon-alpha-n1 experience a transient 'inf luenza-like' syndrome during the first week of treatment. The syndrome , which is dose related and alleviated by paracetamol (acetaminophen), is characterised by fever, chills, and arthralgia. Dose-limiting adve rse effects occurring during longer term interferon-alpha-n1 therapy i nclude fatigue, myalgia, headache, depression, pruritus and seizures. Neutropenia and thrombocytopenia may also occur during interferon-alph a-n1 treatment. Autoimmune thyroid disease may develop in up to 9% of patients treated with interferon-alpha-n1 for greater than or equal to 6 months. At present, interferon-alpha-n1 and the recombinant forms o f interferon-alpha are the only drugs available for the treatment of a dults with well-compensated hepatitis B or C. Interferon-alpha-n1 prod uces moderate response rates in adults with well-compensated chronic h epatitis B or C. Thus, it is positioned alongside recombinant interfer on-alpha products as a useful first-line treatment option for patients with chronic hepatitis B or C.