Effect of neutralizing antibodies on biomarker responses to interferon beta  

Oleh:

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

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Neurology (Official Journal of The American Academy of Neurology) vol. 73 no. 18 (Nov. 2009), page 1493-1500.
Topik: myxovirus resistance protein A; interferon beta

Ketersediaan

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

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Isi artikel

Background: Interferon beta (IFNß) effectively reduces disease activity in patients with multiple sclerosis (MS). Neutralizing antibodies (NAbs) can diminish or abolish the clinical efficacy of IFNß therapies. Biomarkers of the IFNß response, such as myxovirus resistance protein A (MxA), viperin, and interferon-induced protein with tetratricopeptide repeats 1 (IFIT-1), may be used to measure the in vivo effects of NAbs on IFNß bioactivity. Methods: In this multicenter, open-label study, antibody status was measured at screening, and then antibody status, levels of MxA, viperin, and IFIT-1 were measured at baseline (=8 weeks after screening) and 6 months after baseline in patients with relapsing forms of MS treated with IM IFNß-1a, subcutaneous (SC) IFNß-1a, or IFNß-1b. Results: Treatment with IM IFNß-1a was associated with a lower rate of NAb formation among 718 patients screened (p < 0.0001 vs SC IFNß-1a 22 µg, 44 µg, and IFNß-1b). At baseline, patients who were binding antibody positive (BAb+)/neutralizing antibody positive (NAb+) had lower MxA, viperin, and IFIT-1 response compared with BAb-negative (BAb–)/NAb-negative (NAb–) patients (all p < 0.0001). Analyses stratified by NAb titer level among BAb+/NAb+ patients showed diminished biomarker response in patients with NAb titers from 20 to 99 tenfold reduction units (TRU) and abolished response in patients with NAb titers =100 TRU compared with BAb–/NAb– patients. A majority of patients BAb+/NAb+ at screening remained BAb+/NAb+ throughout the study, and biomarker responses remained consistently depressed in these patients at month 6. Conclusions: These data provide evidence that high titers of neutralizing antibodies abolish the in vivo response to interferon beta.

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