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NEUROLOGY 2009;73:1485-1492
© 2009 American Academy of Neurology

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

Andrew R. Pachner, MD, Diego Cadavid, MD, Leo Wolansky, MD and Joan Skurnick, PhD

From the University of Medicine and Dentistry of New Jersey–New Jersey Medical School, Newark, NJ.

Address correspondence and reprint requests to Dr. Andrew R. Pachner, UMDNJ–New Jersey Medical School, 185 South Orange Ave., MSBH506, Newark, NJ 07103 pachner{at}umdnj.edu

Background: 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.

Methods: 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.

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 IFNβ as manifested by diminished reductions in enhancing lesions on MRI.

Conclusions: High levels of anti–interferon beta (IFNβ) antibodies, which result in diminished bioactivity, are correlated with reduced therapeutic efficacy of IFNβ.

Abbreviations: aIFN Ab = anti–interferon beta antibody; BAb = binding antibody; BECOME = Betaseron Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints; BH = black hole; CPE = cytopathic effect; EL = enhancing lesion; GA = glatiramer acetate; IFNβ = interferon beta; MS = multiple sclerosis; MxA = myxovirus resistance protein A; NAb = neutralizing antibody; RT = reverse transcriptase; UMDNJ = University of Medicine and Dentistry of New Jersey.

Supplemental data at www.neurology.org

See also page 1493

Disclosure: Author disclosures are provided at the end of the article.

Received April 6, 2009. Accepted in final form July 28, 2009.


Related Article

Effect of neutralizing antibodies on biomarker responses to interferon beta: The INSIGHT study
Andrew R. Pachner, John D. Warth, Amy Pace, Susan Goelz On behalf of the INSIGHT investigators
Neurology 2009 73: 1493-1500. [Abstract] [Full Text] [PDF]





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