Anti-interferon antibodies to interferon-alpha 2b: results of comparative assays and clinical perspective.

Previous studies have reported a low (less than 3%) incidence of anti-interferon (IFN) serum neutralizing antibodies following treatment with IFN-alpha 2b. Since this result contrasts with a higher incidence reported with IFN-alpha 2a, the question has been raised whether differences in assay techniques and patient comparability rather than inherent differences in the molecules might account for the reported differences in antibody incidence. In this report two patient groups, 151 hairy cell leukemia (HCL) patients and 101 patients with other malignancies, who have received long-term dosing with IFN-alpha 2b, are reported. The sera of both groups were studied before, during and after treatment by various assay methodologies. Utilizing three assay techniques, a less than 3% overall incidence of serum antibody formation was confirmed in these retested samples. With over 575 samples tested in multiple assays, the radioimmunoassay, as utilized in prior reports, demonstrated 99% agreement with a bioassay. Therefore, prior speculation that the assay technique for IFN-alpha 2b might produce a high false-negative rate was disproven. Additionally, the clinical outcome of these patients also failed to demonstrate a pattern of clinical relapse. In summary, these new analyses confirm the low (less than 3%) incidence of neutralizing antibody development following treatment with IFN-alpha 2b and confirm that no high rates of clinical relapse have developed in patients treated with chronic long-term dosing. Assay methodology does not appear to be a likely explanation for the low incidence of antibody formation reported with IFN-alpha 2. Rather, the unique molecular structure and pharmaceutical formulation of IFN-alpha 2b remains the most likely explanation of its minimal antigenicity.