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

Background: Neutralizing antibodies (NAB) to interferon beta (IFN beta) occ ur 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 8 4 samples were NAB negative, 21 were NAB positive (i.e., titer of greater t han 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 dete ctable NAB, 0.36 ng/10(5) PBL in NAB-positive samples, and 0.27 ng/10(5) PB L in control subjects. There was no significant difference between NAB-posi tive samples and control subjects, otherwise the groups differed significan tly 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 non e of the control samples were SEA detected. Conclusion: The conversion of S EA into NAB depends to some degree on the SEA titer, but other mechanisms m ay be involved. Once NAB have developed, the bioavailability of IFN beta as measured by MxA is completely inhibited.