@article { ISI:000364916600010,
	title = {Predictors of disease activity in 857 patients with MS treated with interferon beta-1b},
	journal = {Journal of Neurology},
	volume = {262},
	number = {11},
	year = {2015},
	pages = {2466-2471},
	publisher = {SPRINGER HEIDELBERG},
	address = {TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY},
	abstract = {<p>Multiple sclerosis (MS) is a chronic demyelinating neurodegenerative disease of the CNS that requires long-term treatment. The identification of patient characteristics that can help predict disease outcomes could improve care for patients with MS. The objective of this study is to identify predictors of disease activity in patients from the BEYOND trial. This regression analysis of patients with relapsing-remitting MS from BEYOND examined the predictive value of patient characteristics at baseline and after 1 year of treatment with interferon beta-1b 250 mu g every other day for clinical and MRI outcomes after year 1 of the study. 857 and 765 patients were included in the analyses of clinical and MRI outcomes, respectively. In multivariate analyses of age, a higher number of relapses in the past 2 years, a parts per thousand yen3 new MRI lesions in the first year, and, especially, a higher number of relapses in year 1 predicted the future occurrence of relapses. By contrast, age, MRI activity, and the presence of neutralizing antibodies in the first year were principally predictive of future MRI activity. In patients with continued clinical disease activity or substantial MRI activity on therapy, an alternative therapeutic approach should be strongly considered.</p>
},
	keywords = {Interferon beta-1b, MRI lesion, multiple sclerosis, Predictor, Relapse},
	doi = {10.1007/s00415-015-7862-9},
	author = {Hartung, HP and Kappos, L and Goodin, DS and O{\textquoteright}Connor, P and Filippi, M and Arnason, B and Comi, G and Cook, S and Jeffery, D and Petkau, J and White, R and Bogumil, T and Beckmann, K and Stemper, B and Suarez, G and Sandbrink, R and Pohl, C}
}
@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}
}
