BACKGROUND: Interferon beta (IFNbeta) effectively reduces disease activity in patients with multiple sclerosis (MS). Neutralizing antibodies (NAbs) can diminish or abolish the clinical efficacy of IFNbeta therapies. Biomarkers of the IFNbeta 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 IFNbeta 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 (< or =8 weeks after screening) and 6 months after baseline in patients with relapsing forms of MS treated with IM IFNbeta-1a, subcutaneous (SC) IFNbeta-1a, or IFNbeta-1b. RESULTS: Treatment with IM IFNbeta-1a was associated with a lower rate of NAb formation among 718 patients screened (p < 0.0001 vs SC IFNbeta-1a 22 microg, 44 microg, and IFNbeta-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 > or =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.
BACKGROUND:Interferon beta (IFNbeta) effectively reduces disease activity in patients with multiple sclerosis (MS). Neutralizing antibodies (NAbs) can diminish or abolish the clinical efficacy of IFNbeta therapies. Biomarkers of the IFNbeta 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 IFNbeta 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 (< or =8 weeks after screening) and 6 months after baseline in patients with relapsing forms of MS treated with IM IFNbeta-1a, subcutaneous (SC) IFNbeta-1a, or IFNbeta-1b. RESULTS: Treatment with IM IFNbeta-1a was associated with a lower rate of NAb formation among 718 patients screened (p < 0.0001 vs SC IFNbeta-1a 22 microg, 44 microg, and IFNbeta-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 > or =100 TRU compared with BAb-/NAb- patients. A majority of patientsBAb+/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.
Authors: J M Sailstad; L Amaravadi; A Clements-Egan; B Gorovits; H A Myler; R C Pillutla; S Pursuhothama; M Putman; M K Rose; K Sonehara; L Tang; J T Wustner Journal: AAPS J Date: 2014-03-29 Impact factor: 4.009
Authors: Antonio Bertolotto; Marco Capobianco; Maria Pia Amato; Elisabetta Capello; Ruggero Capra; Diego Centonze; Maria Di Ioia; Antonio Gallo; Luigi Grimaldi; Luisa Imberti; Alessandra Lugaresi; Chiara Mancinelli; Maria Giovanna Marrosu; Lucia Moiola; Enrico Montanari; Silvia Romano; Luigina Musu; Damiano Paolicelli; Francesco Patti; Carlo Pozzilli; Silvia Rossi; Marco Salvetti; Gioachino Tedeschi; Maria Rosaria Tola; Maria Trojano; Maria Troiano; Mauro Zaffaroni; Simona Malucchi Journal: Neurol Sci Date: 2013-12-29 Impact factor: 3.307
Authors: Sunny Malhotra; Marta F Bustamante; Francisco Pérez-Miralles; Jordi Rio; Mari Carmen Ruiz de Villa; Esteban Vegas; Lara Nonell; Florian Deisenhammer; Nicolás Fissolo; Ramil N Nurtdinov; Xavier Montalban; Manuel Comabella Journal: PLoS One Date: 2011-08-23 Impact factor: 3.240
Authors: Stanley L Cohan; Barry A Hendin; Anthony T Reder; Kyle Smoot; Robin Avila; Jason P Mendoza; Bianca Weinstock-Guttman Journal: CNS Drugs Date: 2021-07-06 Impact factor: 5.749