Efficacy and Safety of Natalizumab in Multiple Sclerosis
Background Clinical trials established the efficacy and safety of natalizumab. Data are needed over longer periods of time and in the clinical practice setting.
Objective To evaluate long-term safety of natalizumab and its impact on annualised relapse rate and Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods The Tysabri (natalizumab) Observational Program (TOP) is an open-label, multinational, 10-year prospective study in clinical practice settings.
Results In this 5-year interim analysis, 4821 patients were enrolled. Follow-up for at least 4 years from natalizumab commencement in 468 patients and at least 2 years in 2496 patients revealed no new safety signals. There were 18 cases of progressive multifocal leucoencephalopathy reported, following 11–44 natalizumab infusions. Mean annualised relapse rate decreased from 1.99 in the 12 months prior to baseline to 0.31 on natalizumab therapy (p<0.0001), remaining low at 5 years. Lower annualised relapse rates were observed in patients who used natalizumab as first MS therapy, in patients with lower baseline EDSS scores, and in patients with lower prenatalizumab relapse rates. Mean EDSS scores remained unchanged up to 5 years.
Conclusions Interim TOP data confirm natalizumab's overall safety profile and the low relapse rate and stabilised disability levels in natalizumab-treated patients with RRMS in clinical practice.
Natalizumab (Tysabri, Biogen Idec Inc, Cambridge, Massachusetts, USA) is a selective adhesion molecule inhibitor that blocks α4 integrin, which is expressed on the surface of lymphocytes and is required for endothelial adhesion, facilitating migration of peripheral blood lymphocytes into the central nervous system.
In the 2-year, phase 3 AFFIRM study of patients with relapsing-remitting multiple sclerosis (RRMS), natalizumab monotherapy demonstrated consistent efficacy in the overall study population and across multiple subgroups of patients predefined on the basis of demographic and baseline disease characteristics, including age, sex, number of brain MRI lesions, disability status and number of relapses in the prior year.
While the AFFIRM trial established the safety and efficacy of natalizumab, data are needed to confirm the safety and efficacy of natalizumab over treatment durations longer than 2 years and, importantly, in a clinical practice setting.
The Tysabri (natalizumab) Observational Program (TOP) was designed to evaluate the long-term safety of natalizumab monotherapy, as well as its impact on disease activity and disability progression, in patients with RRMS in the clinical practice setting. This paper presents findings from an interim analysis of TOP data from study initiation in July 2007 to a data lock on 1 December 2012.
Abstract and Introduction
Abstract
Background Clinical trials established the efficacy and safety of natalizumab. Data are needed over longer periods of time and in the clinical practice setting.
Objective To evaluate long-term safety of natalizumab and its impact on annualised relapse rate and Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods The Tysabri (natalizumab) Observational Program (TOP) is an open-label, multinational, 10-year prospective study in clinical practice settings.
Results In this 5-year interim analysis, 4821 patients were enrolled. Follow-up for at least 4 years from natalizumab commencement in 468 patients and at least 2 years in 2496 patients revealed no new safety signals. There were 18 cases of progressive multifocal leucoencephalopathy reported, following 11–44 natalizumab infusions. Mean annualised relapse rate decreased from 1.99 in the 12 months prior to baseline to 0.31 on natalizumab therapy (p<0.0001), remaining low at 5 years. Lower annualised relapse rates were observed in patients who used natalizumab as first MS therapy, in patients with lower baseline EDSS scores, and in patients with lower prenatalizumab relapse rates. Mean EDSS scores remained unchanged up to 5 years.
Conclusions Interim TOP data confirm natalizumab's overall safety profile and the low relapse rate and stabilised disability levels in natalizumab-treated patients with RRMS in clinical practice.
Introduction
Natalizumab (Tysabri, Biogen Idec Inc, Cambridge, Massachusetts, USA) is a selective adhesion molecule inhibitor that blocks α4 integrin, which is expressed on the surface of lymphocytes and is required for endothelial adhesion, facilitating migration of peripheral blood lymphocytes into the central nervous system.
In the 2-year, phase 3 AFFIRM study of patients with relapsing-remitting multiple sclerosis (RRMS), natalizumab monotherapy demonstrated consistent efficacy in the overall study population and across multiple subgroups of patients predefined on the basis of demographic and baseline disease characteristics, including age, sex, number of brain MRI lesions, disability status and number of relapses in the prior year.
While the AFFIRM trial established the safety and efficacy of natalizumab, data are needed to confirm the safety and efficacy of natalizumab over treatment durations longer than 2 years and, importantly, in a clinical practice setting.
The Tysabri (natalizumab) Observational Program (TOP) was designed to evaluate the long-term safety of natalizumab monotherapy, as well as its impact on disease activity and disability progression, in patients with RRMS in the clinical practice setting. This paper presents findings from an interim analysis of TOP data from study initiation in July 2007 to a data lock on 1 December 2012.
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