IngentaConnect A case study on the effect of neutralizing antibodies to interfer...

Authors: Chiu, A. W.¹; Ehrmantraut, M.¹; Richert, N. D.¹; Ikonomidou, V. N.¹; Pellegrini, S.¹; McFarland, H. F.¹; Frank, J. A.²; Bagnato, F.

Source: Clinical & Experimental Immunology, Volume 150, Number 1, October 2007 , pp. 61-67(7)

Publisher: Blackwell Publishing

Abstract:

Summary

Interferon beta (IFN-β) is among the first-line treatment options for patients with multiple sclerosis (MS). A potential caveat of therapy, however, is the development of neutralizing antibodies (NAb) and/or neutralizing activity (NA) non-antibody mediated, although debate is still ongoing as to whether NAb significantly hampers the efficacy of the drug or rather represents an immunologically irrelevant epiphenomenon. In the present study, we describe the effect of NAb on IFN-β-1b through clinical and magnetic resonance imaging (MRI) outcome measures of five relapsing-remitting multiple sclerosis (RRMS) patients who were treated with 250 μg of subcutaneously administered IFN-β-1b every other day and developed NAb at varying titres and times during the course of therapy. Despite the small number of NAb⁺ patients, heterogeneity in MRI/clinical response to IFN-β-1b was identified. Response to IFN-β-1b therapy was observed in the absence or presence of NAb. Also observed was failure to IFN-β-1b coincident with high and sustained NAb titres, but also before NAb development or in the presence of low NAb titres. Multiple MRI and NAb measurements performed within the same individual allow for a better description of the complex heterogeneous response to IFN-β-1b with respect to NAb occurrence.

Keywords: IFN-β; magnetic resonance imaging; multiple sclerosis; neutralizing antibodies

Document Type: Research article

DOI: 10.1111/j.1365-2249.2007.03467.x

Affiliations: 1: Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA, and 2: Laboratory of Diagnostic Radiology and Research, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA

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A case study on the effect of neutralizing antibodies to interferon beta 1b in multiple sclerosis patients followed for 3 years with monthly imaging