title: The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.
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.
authors.affiliation: Dept. of Neurology, St. Vincent's University Hospital, Dublin, Ireland. mhutchin@iol.ie
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchinson
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
authors.forename: Christian
authors.initials: C
authors.lastname: Confavreux
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.forename: Steven L
authors.initials: SL
authors.lastname: Galetta
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.forename: Fred D
authors.initials: FD
authors.lastname: Lublin
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.forename: Paul W
authors.initials: PW
authors.lastname: O'Connor
authors.forename: J Theodore
authors.initials: JT
authors.lastname: Phillips
authors.forename: Chris H
authors.initials: CH
authors.lastname: Polman
authors.forename: Ernst-Wilhelm
authors.initials: EW
authors.lastname: Radue
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rudick
authors.forename: William H
authors.initials: WH
authors.lastname: Stuart
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wajgt
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Wynn
authors.forename: Frances
authors.initials: F
authors.lastname: Lynn
authors.forename: Michael A
authors.initials: MA
authors.lastname: Panzara
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018450:Disease Progression; D005260:Female; D005682:Gadolinium; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000069442:Natalizumab; D016016:Proportional Hazards Models; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D016899:Interferon-beta; D005682:Gadolinium; D000068556:Interferon beta-1a