Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). Issue 6 (31st March 2020)

• Record Type: Journal Article
• Authors: Butzkueven, Helmut; Kappos, Ludwig; Wiendl, Heinz; Trojano, Maria; Spelman, Tim; Chang, Ih; Kasliwal, Rachna; Jaitly, Seema; Campbell, Nolan; Ho, Pei-Ran; Licata, Stephanie
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• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 91:Issue 6(2020)
• Page Start: 660
• Page End: 668
• Publication Date: 2020-03-31
• Subjects: Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2019-322326
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : 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 .