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Title
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Long-term safety and effectiveness of natalizumab treatment in clinical practice : 10 years of real-world data from the Tysabri Observational Program (TOP)
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Author
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Institution/Organisation
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Tysabri Observational Program (TOP) Investigators
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Abstract
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| Objective: The Tysabri Observational Programme (TOP), which began >10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients. Methods: These data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP. Results: As of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced ≥1 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab's known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0-11.6) years; median follow-up time was 5.2 (range 0-10.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias. Conclusions: Since the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab. Trial registration number: NCT00493298. |
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Language
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English
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Source (journal)
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Journal of neurology, neurosurgery and psychiatry. - London
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Publication
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London
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2020
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ISSN
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0022-3050
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DOI
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10.1136/JNNP-2019-322326
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Volume/pages
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91
:6
(2020)
, p. 660-668
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ISI
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000539061900015
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Pubmed ID
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32234967
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Full text (Publisher's DOI)
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Full text (open access)
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