Journal Article

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

Panzara, M. A., Galetta, S. L., Polman, C. H., Hutchinson, M., Phillips, J. T., Wynn, D. R., Radue, E.-W., Havrdova, E., Lynn, F., Wajgt, A., Confavreux, C., Stuart, W. H., Weinstock-Guttman, B., Kappos, L., Rudick, R. A., Lublin, F. D., Miller, D. H., Giovannoni, G., Calabresi, P. A., O’Connor, P. W.

2009

Overview

The AFFIRM and SENTINEL studies showed that natalizumab was effective both as monotherapy and in combination with interferon beta (IFNβ)-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, ≥ 3), Expanded Disability Status Scale score (≤ 3.5, > 3.5), number of T2 lesions (< 9, ≥ 9), presence of gadolinium-enhancing (Gd+) lesions (0, ≥ 1), age (< 40, ≥ 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., ≥ 2 relapses in the year before study entry and ≥ 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: ≥ 9 T2 lesions at baseline, ≥ 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 IFNβ-1a treatment. These results indicate that natalizumab is effective in reducing disability progres- sion and relapses in patients with relapsing MS, particularly in patients with highly active disease.

• Publisher: Steinkopff-Verlag,Springer,Springer Nature B.V
• Subject: Adolescent / Adult / Antibodies, Monoclonal - therapeutic use / Antibodies, Monoclonal, Humanized / Biological and medical sciences / Disease Progression / Female / Gadolinium / Hospitals / Humans / Immunologic Factors - therapeutic use / Interferon / Interferon beta-1a / Interferon-beta - therapeutic use / Kaplan-Meier Estimate / Leukocytes / Male / Medical sciences / Medicine / Medicine & Public Health / Middle Aged / Multiple sclerosis / Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis / Multiple Sclerosis, Relapsing-Remitting - drug therapy / Multiple Sclerosis, Relapsing-Remitting - pathology / Multiple Sclerosis, Relapsing-Remitting - physiopathology / Natalizumab / Neurology / Neuroradiology / Neurosciences / Original Communication / Patients / Proportional Hazards Models / Recurrence / Severity of Illness Index / Treatment Outcome / Young Adult