The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.
Authors
Hutchinson, MichaelKappos, Ludwig
Calabresi, Peter A
Confavreux, Christian
Giovannoni, Gavin
Galetta, Steven L
Havrdova, Eva
Lublin, Fred D
Miller, David H
O'Connor, Paul W
Phillips, J Theodore
Polman, Chris H
Radue, Ernst-Wilhelm
Rudick, Richard A
Stuart, William H
Wajgt, Andrzej
Weinstock-Guttman, Bianca
Wynn, Daniel R
Lynn, Frances
Panzara, Michael A
Affiliation
Dept. of Neurology, St. Vincent's University Hospital, Dublin, Ireland., mhutchin@iol.ieIssue Date
2012-02-01T10:31:51ZMeSH
AdolescentAdult
Antibodies, Monoclonal/*therapeutic use
Antibodies, Monoclonal, Humanized
Disease Progression
Female
Gadolinium
Humans
Immunologic Factors/*therapeutic use
Interferon-beta/therapeutic use
Kaplan-Meier Estimate
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting/*drug therapy/pathology/physiopathology
Proportional Hazards Models
Recurrence
Severity of Illness Index
Treatment Outcome
Young Adult
Metadata
Show full item recordCitation
J Neurol. 2009 Mar;256(3):405-15. Epub 2009 Mar 18.Journal
Journal of neurologyDOI
10.1007/s00415-009-0093-1PubMed ID
19308305Abstract
The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNbeta)-1a in patients with relapsing multiple sclerosis (MS). Further analyses of AFFIRM and SENTINEL data were conducted to determine the efficacy of natalizumab in prespecified patient subgroups according to baseline characteristics: relapse history 1 year before randomization (1, 2, > or = 3), Expanded Disability Status Scale score (< or = 3.5, > 3.5), number of T2 lesions (< 9, > or = 9), presence of gadolinium-enhancing (Gd+) lesions (0, > or = 1), age (< 40, > or = 40) and gender (male, female). A post hoc analysis was conducted to determine the efficacy of natalizumab in patients with highly active disease (i. e., > or = 2 relapses in the year before study entry and > or = 1 Gd+ lesion at study entry). In both AFFIRM and SENTINEL studies natalizumab reduced the annualized relapse rates across all subgroups (except the small subgroups with < 9 baseline T2 lesions) over 2 years. In AFFIRM, natalizumab significantly reduced the risk of sustained disability progression in most subgroups. In SENTINEL, natalizumab significantly reduced the risk of sustained disability progression in the following subgroups: > or = 9 T2 lesions at baseline, > or = 1 Gd+ lesions at baseline, female patients and patients < 40 years of age. Natalizumab reduced the risk of disability progression by 64 % and relapse rate by 81 % in treatment- naive patients with highly active disease and by 58 % and 76 %, respectively, in patients with highly active disease despite IFNbeta-1a treatment. These results indicate that natalizumab is effective in reducing disability progression and relapses in patients with relapsing MS, particularly in patients with highly active disease.Language
engISSN
1432-1459 (Electronic)0340-5354 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1007/s00415-009-0093-1