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- W2063110337 abstract "<b>Background:</b> Interferon beta (IFNβ) 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 IFNβ bioactivity, but there is less evidence that NAbs impact clinical efficacy of the drug. <b>Methods:</b> Because a robust effect of IFNβ 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 IFNβ-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 IFNβ bioactivity by myxovirus resistance protein A gene expression and identified 2 groups of patients: one labeled “bioactivity preserved,” with absent NAbs and robust IFNβ 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. <b>Results:</b> 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 IFNβ as manifested by diminished reductions in enhancing lesions on MRI. <b>Conclusions:</b> High levels of anti–interferon beta (IFNβ) antibodies, which result in diminished bioactivity, are correlated with reduced therapeutic efficacy of IFNβ." @default.
- W2063110337 created "2016-06-24" @default.
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- W2063110337 date "2009-11-02" @default.
- W2063110337 modified "2023-09-26" @default.
- W2063110337 title "Effect of anti-IFN antibodies on MRI lesions of MS patients in the BECOME study" @default.
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- W2063110337 doi "https://doi.org/10.1212/wnl.0b013e3181bf9919" @default.
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