The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analyses of AFFIRM and SENTINEL.
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.
Hutchinson
Michael
M
Dept. of Neurology, St. Vincent's University Hospital, Dublin, Ireland. mhutchin@iol.ie
Kappos
Ludwig
L
Calabresi
Peter A
PA
Confavreux
Christian
C
Giovannoni
Gavin
G
Galetta
Steven L
SL
Havrdova
Eva
E
Lublin
Fred D
FD
Miller
David H
DH
O'Connor
Paul W
PW
Phillips
J Theodore
JT
Polman
Chris H
CH
Radue
Ernst-Wilhelm
EW
Rudick
Richard A
RA
Stuart
William H
WH
Wajgt
Andrzej
A
Weinstock-Guttman
Bianca
B
Wynn
Daniel R
DR
Lynn
Frances
F
Panzara
Michael A
MA
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D016899:Interferon-beta; D005682:Gadolinium; D000068556:Interferon beta-1a