Effect of anti-IFNß antibodies on MRI lesions of MS patients in the BECOME study  

Oleh:

Pachner, Andrew R. ; Cadavid, Diego ; Wolansky, Leo ; Skurnick, Joan

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Neurology (Official Journal of The American Academy of Neurology) vol. 73 no. 18 (Nov. 2009), page 1485-1492.
Topik: glatiramer acetate; interferon beta; myxovirus resistance protein A

Ketersediaan

Perpustakaan FK Nomor Panggil: N11.K.2009.07 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Background: Interferon beta (IFNß) administered subcutaneously is immunogenic in some patients with multiple sclerosis (MS) and leads to the development of neutralizing antibodies (NAbs). Considerable evidence has accumulated that NAbs diminish or abolish IFNß bioactivity, but there is less evidence that NAbs impact clinical efficacy of the drug. Methods: Because a robust effect of IFNß is a decrease in enhancing lesions on brain MRI scans, the Betaseron Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints (BECOME) study, a head-to-head study of IFNß-1b vs glatiramer acetate with a primary endpoint of enhancing lesions on MRI, provided an excellent opportunity to determine the effect of NAbs on MRI activity. We measured NAbs and IFNß bioactivity by myxovirus resistance protein A gene expression and identified 2 groups of patients: one labeled "bioactivity preserved," with absent NAbs and robust IFNß bioactivity (n = 8), and the other labeled "bioactivity lost," with high levels of NAbs and diminished bioactivity (n = 7). The development of enhancing lesions in the groups was then compared. Results: The incidence of NAbs and effect of NAbs on bioactivity were consistent with previous studies. We analyzed MRI outcomes in patients with NAbs at levels high enough to abolish bioactivity relative to patients without NAbs. For the preserved bioactivity group, the enhancing lesion/scan ratio decreased from 7.6 in the pretreatment period to 2.6 in the posttreatment period, a 66% decrease. For the lost bioactivity group, the decrease was 8.5 to 5.8, only a 32% decrease. Thus, lost bioactivity from high levels of NAbs resulted in reduced therapeutic efficacy of IFNß as manifested by diminished reductions in enhancing lesions on MRI. Conclusions: High levels of anti–interferon beta (IFNß) antibodies, which result in diminished bioactivity, are correlated with reduced therapeutic efficacy of IFNß.

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