The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.

Hdl Handle:
http://hdl.handle.net/10147/207577
Title:
The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.
Authors:
Hutchinson, Michael; Kappos, 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.ie
Citation:
J Neurol. 2009 Mar;256(3):405-15. Epub 2009 Mar 18.
Journal:
Journal of neurology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207577
DOI:
10.1007/s00415-009-0093-1
PubMed ID:
19308305
Abstract:
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:
eng
MeSH:
Adolescent; Adult; 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
ISSN:
1432-1459 (Electronic); 0340-5354 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorHutchinson, Michaelen_GB
dc.contributor.authorKappos, Ludwigen_GB
dc.contributor.authorCalabresi, Peter Aen_GB
dc.contributor.authorConfavreux, Christianen_GB
dc.contributor.authorGiovannoni, Gavinen_GB
dc.contributor.authorGaletta, Steven Len_GB
dc.contributor.authorHavrdova, Evaen_GB
dc.contributor.authorLublin, Fred Den_GB
dc.contributor.authorMiller, David Hen_GB
dc.contributor.authorO'Connor, Paul Wen_GB
dc.contributor.authorPhillips, J Theodoreen_GB
dc.contributor.authorPolman, Chris Hen_GB
dc.contributor.authorRadue, Ernst-Wilhelmen_GB
dc.contributor.authorRudick, Richard Aen_GB
dc.contributor.authorStuart, William Hen_GB
dc.contributor.authorWajgt, Andrzejen_GB
dc.contributor.authorWeinstock-Guttman, Biancaen_GB
dc.contributor.authorWynn, Daniel Ren_GB
dc.contributor.authorLynn, Francesen_GB
dc.contributor.authorPanzara, Michael Aen_GB
dc.date.accessioned2012-02-01T10:31:51Z-
dc.date.available2012-02-01T10:31:51Z-
dc.date.issued2012-02-01T10:31:51Z-
dc.identifier.citationJ Neurol. 2009 Mar;256(3):405-15. Epub 2009 Mar 18.en_GB
dc.identifier.issn1432-1459 (Electronic)en_GB
dc.identifier.issn0340-5354 (Linking)en_GB
dc.identifier.pmid19308305en_GB
dc.identifier.doi10.1007/s00415-009-0093-1en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207577-
dc.description.abstractThe 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdolescenten_GB
dc.subject.meshAdulten_GB
dc.subject.meshAntibodies, Monoclonal/*therapeutic useen_GB
dc.subject.meshAntibodies, Monoclonal, Humanizeden_GB
dc.subject.meshDisease Progressionen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGadoliniumen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunologic Factors/*therapeutic useen_GB
dc.subject.meshInterferon-beta/therapeutic useen_GB
dc.subject.meshKaplan-Meier Estimateen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshMultiple Sclerosis, Relapsing-Remitting/*drug therapy/pathology/physiopathologyen_GB
dc.subject.meshProportional Hazards Modelsen_GB
dc.subject.meshRecurrenceen_GB
dc.subject.meshSeverity of Illness Indexen_GB
dc.subject.meshTreatment Outcomeen_GB
dc.subject.meshYoung Adulten_GB
dc.titleThe efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.en_GB
dc.contributor.departmentDept. of Neurology, St. Vincent's University Hospital, Dublin, Ireland., mhutchin@iol.ieen_GB
dc.identifier.journalJournal of neurologyen_GB
dc.description.provinceLeinster-

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