Clinical experience in a large cohort of multiple sclerosis patients treated with natalizumab.
|Title||Clinical experience in a large cohort of multiple sclerosis patients treated with natalizumab.|
|Publication Type||Journal Article|
|Authors||Wundes A, Lucas S, Krasucki D, Woolvett V, Hillman L, Kraft GH, Johnson S, Stobbe G|
|Journal||International Journal of MS Care|
Background: Management of active relapsing-remitting multiple sclerosis (MS) continues to pose a therapeutic challenge. Natalizumab (Tysabri) is a humanized monoclonal antibody that blocks trafficking of lymphocytes into the brain by alpha-4 integrin-mediated adhesion. Although it is generally considered to be particularly effective and well tolerated, patients may develop natalizumab antibodies, allergic reactions, progressive multifocal leukoencephalopathy (PML), and other opportunistic infections. Objective: To examine natalizumab in the clinical setting. Design/Methods: A cohort of 146 MS patients receiving up to 31 monthly doses natalizumab (mean, 16) was evaluated clinically, by magnetic resonance imaging (MRI), and by laboratory monitoring. Results: Twenty-seven patients (18.5%) discontinued treatment; reasons included disease progression (n = 7), hypersensitivity (n = 6), other side effects (n = 3), patient request (n = 4), and pregnancy/intended conception (n = 2). Natalizumab- antibody positivity occurred in seven patients who had hypersensitivity reactions or disease progression, four of whom were previously exposed to 1 to 2 doses before withdrawal from the market in 2005. In contrast, anti-natalizumab antibodies were negative when routinely assessed at 1 year (n = 70). Clinical status and MRI findings were essentially unchanged. Immunological monitoring demonstrated a statistically significant decline in CD4/CD8 ratios at 1 year (mean baseline, 2.8 vs 2.2; P < .033). The CD4 percentage decreased (mean, 52.5 vs 46.5) at 1 month; absolute CD4 (mean, 0.9 vs 1.2 thousand/µL) and CD8 counts (mean, 0.4 vs 0.6 thousand/µL) increased at 1 month. These changes were sustained (CD4 percentage, absolute CD8) or modestly further increased (absolute CD4) for up to 24 months. Conclusion/Relevance: Natalizumab was found to be effective in stabilizing the clinical course in the majority of cases. Our data do not provide a rationale for routine antibody testing unless patients develop hypersensitivity or disease progression or upon re-exposure after short-term natalizumab use. The clinical relevance of changes in T-cell subsets remains unclear at this point; it is unknown whether monitoring may contribute to early PML detection.