Interferon beta-1b serum levels in multiple sclerosis patients following subcutaneous administration

Abstract

Recombinant interferon beta-1b (rIFN beta) reduces the frequency of exacerbations in relapsing-remitting MS when administered subcutaneously on alternate days. However, the pharmacokinetics of rIFN beta are not well understood and there are scant data on the detectability of rIFN beta in the serum of MS patients following subcutaneous administration. Moreover, existing assays for detecting IFN beta are biologic, time-consuming, and require handling of infectious agents. We developed and standardized an ELISA specific for measuring rIFN beta with a detection range of 40 to 1,000 IU/ml. The specificity of our ELISA was confirmed by the lack of cross-reactivity with other cytokines, including IFN alpha, IFN gamma, IFN Consensus-1, and TNF alpha. We screened serum from 34 MS patients drawn within 12-36 hours of treatment: 15 patients taking 8 MIU, four patients taking 1.6 MIU, and 15 patients taking placebo. Eleven of the 15 patients in the 8-MIU treatment group had measurable rIFN beta serum levels ranging from 120 to 475 MIU/ml. Two of four patients in the 1.6-MIU treatment group, but none of the placebo group, had detectable serum rIFN beta levels. A small prospective time-course study was carried out in four MS patients receiving rIFN beta. Serial blood samples were obtained prior to and 4, 8, 24, and 48 hours after rIFN beta injection. A peak serum rIFN beta level was observed between 8 and 24 hours after rIFN beta injection and tended to decline to near preinjection levels at 48 hours postinjection. These results are consistent with the rationale of alternate-day, subcutaneous administration of rIFN beta. In addition, the ELISA described might be a useful tool to study the pharmacokinetics and the relationship of rIFN beta serum levels to clinical efficacy.NEUROLOGY 1996;46: 1639-1643