Effect of neutralizing antibodies on biomarker responses to interferon beta

Pachner, Andrew R.; Warth, John D.; Pace, Amy; Goelz, Susan

doi:10.1212/wnl.0b013e3181bf98db

Cited by 55 publications

(37 citation statements)

References 34 publications

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“…There is robust evidence that NAbs reduce IFN-β bioactivity, as measured using the biomarker MxA Pachner et al 2009). Most studies have used the CPE assay to measure MxA.…”

Section: Discussionmentioning

confidence: 99%

Neutralizing Antibodies Are Associated with a Reduction of Interferon-β Efficacy during the Treatment of Japanese Multiple Sclerosis Patients

Sato

Nakashima

Fukazawa

et al. 2012

Tohoku J. Exp. Med.

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Multiple sclerosis (MS) is a chronic immune-mediated inflammatory demyelinating disease of the central nervous system. Interferon-β (IFN-β) has been used as the first line therapy for MS treatment in Japan, but patients treated with IFN-β may develop antibodies, known as neutralizing antibodies (NAbs), which abrogate its therapeutic effects. Intramuscular IFN-β 1a and subcutaneous IFN-β 1b are currently available in Japan, but large-scale studies evaluating the prevalence and clinical implications of NAbs against these IFN-β preparations in MS patients have only been performed in Caucasian populations. NAbs positivity has been reported to be associated with HLA-DRB1 alleles, suggesting that the positivity might differ among populations with distinct genetic backgrounds. Clinical information and sera were collected from 229 consecutive MS patients treated with IFN-β in 4 centers in Japan. Sera were tested for NAbs using a luciferase reporter gene assay. In total, 5.2% of IFN-β-1a-treated patients (4/77) and 30.3% of IFN-β-1b-treated patients (46/152) were positive for Nabs. The frequency of NAbs was highest in patients treated for 13 to 24 months. Clinical relapse and contrast-enhancing lesions in the magnetic resonance imaging increased together with NAbs titers in this group. In conclusion, the prevalence of NAbs in Japanese MS patients is similar to that in Caucasian populations and is associated with an increase in disease activity. Therefore, routine NAbs testing is recommended also in Asian populations to ensure the early identification of patients who would benefit from a change in therapy.

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“…There is robust evidence that NAbs reduce IFN-β bioactivity, as measured using the biomarker MxA Pachner et al 2009). Most studies have used the CPE assay to measure MxA.…”

Section: Discussionmentioning

confidence: 99%

Neutralizing Antibodies Are Associated with a Reduction of Interferon-β Efficacy during the Treatment of Japanese Multiple Sclerosis Patients

Sato

Nakashima

Fukazawa

et al. 2012

Tohoku J. Exp. Med.

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“…Testing for NAB against IFN-␤ can be of help in this decision-making process, especially when breakthrough disease occurred during previous IFN-␤ treatment. There is accumulating evidence that persistent high titres of NABs against IFN-␤ reduce the biological activity of IFN-␤ which is sooner or later associated with an increase in disease activity [12] . Thus, the European Neurological Society recommended routine NAB testing [13] .…”

Section: Discussionmentioning

confidence: 99%

Natalizumab and Beyond

Yıldız¹,

Tettenborn²,

Putzki³

2010

Eur Neurol

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“…Like other proteinbased disease-modifying agents IFN-beta exhibits immunogenicity [17]. It has been shown in several studies that neutralizing antibodies (NAbs) against IFN-beta reverse the induction of IFN-beta induced molecules and, thereby, abolish the biological effects of IFN-beta treatment [18][19][20]. As a result, therapeutic efficacy measured by MRI lesion progression, relapse rate and disability progression declines [21,22].…”

Section: Interferon Betamentioning

confidence: 99%

Treatment of multiple sclerosis: current concepts and future perspectives

Buck

Hemmer

2011

J Neurol

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Currently, several disease-modifying therapies for the treatment of multiple sclerosis are established and more are likely to be introduced. These treatment options differ with respect to their application profile, mechanism of action, efficacy, safety, and tolerance. Here, we review current concepts of MS therapies, report recent results of clinical trials, and discuss emerging treatment options.

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Effect of neutralizing antibodies on biomarker responses to interferon beta

Abstract: These data provide evidence that high titers of neutralizing antibodies abolish the in vivo response to interferon beta.

Cited by 55 publications

References 34 publications

Neutralizing Antibodies Are Associated with a Reduction of Interferon-β Efficacy during the Treatment of Japanese Multiple Sclerosis Patients

Neutralizing Antibodies Are Associated with a Reduction of Interferon-β Efficacy during the Treatment of Japanese Multiple Sclerosis Patients

Natalizumab and Beyond

Treatment of multiple sclerosis: current concepts and future perspectives

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