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

Abstract

Interferon beta (IFN-beta) 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-beta-1b through clinical and magnetic resonance imaging (MRI) outcome measures of five relapsing-remitting multiple sclerosis (RRMS) patients who were treated with 250 mug of subcutaneously administered IFN-beta-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-beta-1b was identified. Response to IFN-beta-1b therapy was observed in the absence or presence of NAb. Also observed was failure to IFN-beta-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-beta-1b with respect to NAb occurrence.

Fig. 1

The graph represents NAb development in relation to tCELs evolution in patient 1. Neutralizing antibodies (Nab) development and total contrast-enhancing lesions (tCELs) occurrence at each time-point. Each arrow under the x-axis refers to one relapse corresponding to the indicated month. In Figs 1–3, each arrow above the x-axis refers to the month when low NAb titres (i.e. < 1 : 400) were detected. High titres are indicated by text corresponding to the arrow. As NAbs were detected in almost every blood sample collected in patients 4 and 5 at each measurement, titres are indicated with white dots. When a dotted line between two dots is not present, NAbs were not detected. Numbering of the figures corresponds to the numbering of the patients (see text in the results section).

Fig. 3

The graph represents NAb development in relation to tCELs evolution in patient 3.

Fig. 5

The graph represents NAb development in relation to tCELs evolution in patient 5.

Fig. 2

The graph represents NAb development in relation to tCELs evolution in patient 2.

Fig. 4

The graph represents NAb development in relation to tCELs evolution in patient 4.