Bioavailability of interferon beta 1b in MS patients with and without neutralizing antibodies

Background: Neutralizing antibodies (NAB) to interferon beta (IFN beta) occur in about one-third of MS patients treated with IFN beta-1b and there is an association with a loss of clinical and MRI efficacy. However, there are no data regarding the bioavailability of IFN beta-1b in patients with and without NAB. Methods: The authors measured MxA in whole blood by ELISA, and serum-binding antibodies (SBA) by Western blot and ELISA in 134 samples of MS patients on IFN beta-1b and 54 control subjects, and correlated the MxA levels and SEA titers with the NAB titer. Results: In the IFN beta group 84 samples were NAB negative, 21 were NAB positive (i.e., titer of greater than or equal to 20), and 29 had detectable NAB (i.e., titer between 10 and 20). The median MxA concentration in NAB-negative patients was 4.09 ng/10(5) peripheral blood leukocytes (PBL), 2.37 ng/10(5) PBL in samples with detectable NAB, 0.36 ng/10(5) PBL in NAB-positive samples, and 0.27 ng/10(5) PBL in control subjects. There was no significant difference between NAB-positive samples and control subjects, otherwise the groups differed significantly from each other. SEA occurred in 49% of NAB-negative samples, in 79% of samples with detectable NAB, and in all NAB-positive samples. With regard to the SEA titer, all groups differed significantly from each other. In none of the control samples were SEA detected. Conclusion: The conversion of SEA into NAB depends to some degree on the SEA titer, but other mechanisms may be involved. Once NAB have developed, the bioavailability of IFN beta as measured by MxA is completely inhibited.