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Erschienen in: Journal of Neurology 4/2014

01.04.2014 | Original Communication

A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis

verfasst von: T. L. Vollmer, P. S. Sorensen, K. Selmaj, F. Zipp, E. Havrdova, J. A. Cohen, N. Sasson, Y. Gilgun-Sherki, D. L. Arnold, On behalf of the BRAVO Study Group

Erschienen in: Journal of Neurology | Ausgabe 4/2014

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Abstract

The phase III placebo-controlled BRAVO study assessed laquinimod effects in patients with relapsing-remitting MS (RRMS), and descriptively compared laquinimod with interferon beta (IFNβ)-1a (Avonex® reference arm). RRMS patients age 18–55 years with Expanded Disability Status Scale (EDSS) scores of 0–5.5 and documented pre-study relapse (≥ 1 in previous year, 2 in previous 2 years, or 1 in previous 1–2 years and ≥ 1 GdE lesion in the previous year) were randomized (1:1:1) to laquinimod 0.6 mg once-daily, matching oral placebo, or IFNβ-1a IM 30 μg once-weekly (rater-blinded design), for 24 months. The primary endpoint was annualized relapse rate (ARR); secondary endpoints included percent brain volume change (PBVC) and 3-month confirmed disability worsening. In all, 1,331 patients were randomized: laquinimod (n = 434), placebo (n = 450), and IFNβ-1a (n = 447). ARR was not significantly reduced with laquinimod [−18 %, risk ratio (RR) = 0.82, 95 % CI 0.66–1.02; p = 0.075] vs. placebo. Laquinimod significantly reduced PBVC (28 %, p < 0.001). Confirmed disability worsening was infrequent (10 % laquinimod, 13 % placebo). The change in confirmed disability worsening with laquinimod measured using EDSS was −31 % [hazard ratio (HR) 0.69, p = 0.063], and using Multiple Sclerosis Functional Composite (MSFC) z-score was −77 % (p = 0.150), vs. placebo. IFNβ-1a reduced ARR 26 % (RR = 0.74, 95 % CI 0.60–0.92, p = 0.007), showed no effect on PBVC loss (+11 %, p = 0.14), and changes in disability worsening were −26 and −66 % as measured using the EDSS (HR 0.742, p = 0.13) and MSFC (p = 0.208), respectively. Adverse events occurred in 75, 82, and 70 % of laquinimod, IFNβ-1a, and placebo patients, respectively. Once-daily oral laquinimod 0.6 mg resulted in statistically nonsignificant reductions in ARR and disability progression, but significant reductions in brain atrophy vs. placebo. Laquinimod was well-tolerated.
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Metadaten
Titel
A randomized placebo-controlled phase III trial of oral laquinimod for multiple sclerosis
verfasst von
T. L. Vollmer
P. S. Sorensen
K. Selmaj
F. Zipp
E. Havrdova
J. A. Cohen
N. Sasson
Y. Gilgun-Sherki
D. L. Arnold
On behalf of the BRAVO Study Group
Publikationsdatum
01.04.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 4/2014
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-014-7264-4

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