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, frequency, and duration of administration; timing and frequency of blood sampling; methods used to determine antibody presence (sensitivity); calculation of the units used to report the results; intrinsic immunogenicity of the protein product; major histocompatibility complex genotype of the challenged individual; associated diseases and medication. Without specification of all these factors, it is difficult to put forward a valid statement from the published literature regarding the comparative incidence of antibodies to various forms of IFN. Furthermore, because units are not standardized and rarely reported, it becomes impossible to make any comparisons of antibody titers. This evaluation confirms, by clinical trial results, the decrease in immunogenicity observed in vitro and in vivo of different IFN-alpha 2a products manufactured between 1989 and 1993 following incremental improvements in process specifications and expanded quality control. Serial serum samples were taken, prepared, stored, and shipped according to identical protocols in five different clinical trials performed with IFN-alpha 2a between 1989 and 1995 in comparable patient populations with chronic hepatitis C. The coded samples were screened using sensitive enzyme immunoassay (EIA). Positive samples were further analyzed and quantified by bioassay [antiviral inhibition assay (AVIA)]. The data from these clinical trials confirm the results from extensive preclinical testing. Refrigerated lyophilisate and a new human serum albumin (HSA)-free formulation of IFN-alpha 2a, produced according to the latest process specification, are less immunogenic than earlier products.