Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP).
- Butzkueven H Department of Neuroscience, Central Clinical School, Alfred Campus, Monash University, Melbourne, Victoria, Australia.
- Kappos L Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland.
- Wiendl H Department of Neurology, University of Münster, Münster, Germany.
- Trojano M Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
- Spelman T Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
- Chang I Biostatistics, Biogen, Cambridge, Massachusetts, USA.
- Kasliwal R Safety and Benefit Risk, Biogen, Cambridge, Massachusetts, USA (at the time of these analyses).
- Jaitly S Safety and Benefit Risk, Biogen, Cambridge, Massachusetts, USA (at the time of these analyses).
- Campbell N Global Medical, Biogen, Cambridge, Massachusetts, USA.
- Ho PR Global Medical, Biogen, Cambridge, Massachusetts, USA.
- Licata S Global Medical, Biogen, Cambridge, Massachusetts, USA stephanie.licata@biogen.com.
- 2020-04-03
Published in:
- Journal of neurology, neurosurgery, and psychiatry. - 2020
Adult
Disability Evaluation
Disease Progression
Female
Humans
Immunologic Factors
Male
Middle Aged
Multiple Sclerosis, Relapsing-Remitting
Natalizumab
Treatment Outcome
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1136/jnnp-2019-322326
- PMID 32234967
- Persistent URL
- https://fredi.hepvs.ch/global/documents/179977
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