CLINICAL INVESTIGATION OF THE IMMUNOGENICITY OF INTERFERON-ALPHA-2A

The following confounding array of variables can affect the reporting of antibodies to interferon (IFN)-alpha or any other protein injected into humans for prophylactic or therapeutic purposes: route, dose, fre quency, and duration of administration; timing and frequency of blood sampling; methods used to determine antibody presence (sensitivity); c alculation of the units used to report the results; intrinsic immunoge nicity of the protein product; major histocompatibility complex genoty pe of the challenged individual; associated diseases and medication, W ithout specification of all these factors, it is difficult to put forw ard a valid statement from the published literature regarding the comp arative incidence of antibodies to various forms of IFN, Furthermore, because units are not standardized and rarely reported, it becomes imp ossible to make any comparisons of antibody titers, This evaluation co nfirms, by clinical trial results, the decrease in immunogenicity obse rved in vitro and in vivo of different IFN-alpha 2a products manufactu red between 1989 and 1993 following incremental improvements in proces s specifications and expanded quality control, Serial serum samples we re taken, prepared, stored, and shipped according to identical protoco ls in five different clinical trials performed with IFN-alpha 2a betwe en 1989 and 1995 in comparable patient populations with chronic hepati tis C, The coded samples were screened using sensitive enzyme immunoas say (EIA), Positive samples were further analyzed and quantified by bi oassay [antiviral inhibition assay (AVIA)], The data from these clinic al trials confirm the results from extensive preclinical testing, Refr igerated lyophilisate and a new human serum albumin (HSA)-free formula tion of IFN-alpha 2a, produced according to the latest process specifi cation, are less immunogenic than earlier products.