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: Michael Hutchinson, Ludwig Kappos, Peter A Calabresi, Christian Confavreux, Gavin Giovannoni, Steven L Galetta, Eva Havrdova, Fred D Lublin, David H Miller, Paul W O'Connor, J Theodore Phillips, Chris H Polman, Ernst-Wilhelm Radue, Richard A Rudick, William H Stuart, Andrzej Wajgt, Bianca Weinstock-Guttman, Daniel R Wynn, Frances Lynn, Michael A Panzara, AFFIRM and SENTINEL Investigators
• Journal: Journal of neurology (J Neurol) Vol. 256 Issue 3 Pg. 405-15 (Mar 2009) ISSN: 1432-1459 [Electronic] Germany
• PMID: 19308305 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Immunologic Factors
• Natalizumab
• Interferon-beta
• Gadolinium
• Interferon beta-1a

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Disease Progression
• Female
• Gadolinium
• Humans
• Immunologic Factors (therapeutic use)
• Interferon beta-1a
• Interferon-beta (therapeutic use)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (drug therapy, pathology, physiopathology)
• Natalizumab
• Proportional Hazards Models
• Recurrence
• Severity of Illness Index
• Treatment Outcome
• Young Adult