Pharmacodynamics of interferon beta in multiple sclerosis patients with or without serum neutralizing antibodies
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- Scagnolari, C., Duda, P., Bagnato, F. et al. J Neurol (2007) 254: 597. doi:10.1007/s00415-006-0332-7
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To analyze the in vivo biological effect of anti-interferon beta (IFN-beta) neutralizing antibodies (NABs), blood concentrations of neopterin, beta2microglobulin (Beta2-MG), mRNA-dependent myxovirusresistant protein A (MxA) and dsRNA-dependent protein kinase (PKR) were measured before (predose) and 24 hours after (postdose) IFN-beta administration in 49 patients with multiple sclerosis (MS) with (n = 25) and without (n = 24) NABs.
The results indicated that predose levels of MxA-mRNA and PKR-mRNA were highly variable [coefficient of variation (CV) > 100%] among patients. A lower inter-individual variability was observed for pre-dose levels of Beta2-MG and neopterin (CVs of 29% and 44%, respectively).
Significantly lower pre- and post-dose blood levels of IFN induced markers, except for postdose PKR-mRNA (p = 0.09), were seen in NAB+ compared with NAB–patients and between patients with high (> 200 t1/10) and low (£ 200 t1/10) NAB titers. A significant inverse correlation between NAB titer and pre-dose levels of the above IFN-induced markers was found. In summary, our findings confirm that NABs affect absolute concentrations of IFN-beta induced markers and suggest that such an effect occurs in a titer-dependent manner.