@article { ISI:000299903700010,
	title = {Neutralizing antibodies to interferon beta-1b in multiple sclerosis: a clinico-radiographic paradox in the BEYOND trial},
	journal = {Multiple Sclerosis Journal},
	volume = {18},
	number = {2},
	year = {2012},
	pages = {181-195},
	publisher = {SAGE PUBLICATIONS LTD},
	address = {1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND},
	abstract = {<p>Background: The frequency and impact of neutralizing antibodies (NAbs) to interferon beta-1b (IFN beta-1b) on clinical and radiographic outcomes is controversial. Objective: To assess NAb impact in the BEYOND study. Methods: 2244 patients were randomized (2:2:1) to receive IFN beta-1b, either 250 or 500 mu g, or glatiramer acetate, 20 mg, and observed for 2-3.5 years. NAb titers were determined every 6 months. A titer \&gt;= 20 NU/ml was considered NAb positive. Efficacy was compared between NAb-positive and NAb-negative patients, using comprehensive statistical analyses, taking into account the delayed appearance of NAbs, the time-dependent changes in the relapse rate, spontaneous reversions to NAb-negative status, NAb-titer level, and also adjusting for baseline factors. Results: In the IFN beta-1b 250 mu g group, NAb-positive titers were detected (\&gt;= once) in 319 patients (37.0\%); of these, 112 (35.1\%) reverted to NAb-negative status. In the IFN beta-1b 500 mu g group, 340 patients (40.7\%) became NAb-positive and 119 (35.0\%) reverted to NAb-negative status. In both IFN beta groups, especially the 250 mu g arm, NAb-positive status was not associated with a convincing impact on any clinical outcome measure by any statistical analysis. By contrast, in both IFN beta groups, NAbs were associated with a very consistent deleterious impact on most MRI outcomes. Conclusion: There was a notable dissociation between the impact of NAbs on MRI and clinical outcomes. On MRI measures, the impact was consistent and convincing, whereas on clinical measures a negative impact of NAbs was not found. The basis for this clinico-radiographic paradox is unknown but it suggests that the relationship between NAbs and the therapeutic effects of IFN beta-1b is complex.</p>
},
	keywords = {BEYOND study, Interferon beta-1b, multiple sclerosis, neutralizing antibodies},
	doi = {10.1177/1352458511418629},
	author = {Goodin, DS and Hartung, HP and O{\textquoteright}Connor, P and Filippi, M and Arnason, B and Comi, G and Cook, S and Jeffery, D and Kappos, L and Bogumil, T and Knappertz, V and Sandbrink, R and Beckmann, K and White, R and Petkau, J and Pohl, C}
}
