Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results

Helmut Butzkueven, Ludwig Kappos, Fabio Pellegrini, Maria Trojano, Heinz Wiendl, Radhika N Patel, Annie Zhang, Christophe Hotermans, Shibeshih Belachew, TYSABRI Observational Program (TOP) Investigators, Helmut Butzkueven, Ludwig Kappos, Fabio Pellegrini, Maria Trojano, Heinz Wiendl, Radhika N Patel, Annie Zhang, Christophe Hotermans, Shibeshih Belachew, TYSABRI Observational Program (TOP) Investigators

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.

Trial registration number: NCT00493298.

Keywords: Multiple Sclerosis.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Figures

Figure 1
Figure 1
Annualised relapse rate on natalizumab therapy: per yearly interval over time (n=4821). Error bars indicate 95% CIs. Data beyond 5 years are excluded.
Figure 2
Figure 2
Annualised relapse rate after initiation of natalizumab according to (A) baseline characteristics, (B) combined baseline relapse status and number of prior disease-modifying therapies (DMTs) and (C) baseline treatment history.*p Value from a negative binomial regression model adjusted for sex, baseline EDSS score (1), prior DMT use (0, 1 and >1), disease duration (≥8 vs 1), EDSS score (

Figure 3

(A) Time from first natalizumab…

Figure 3

(A) Time from first natalizumab infusion to confirmed EDSS progression in overall study…

Figure 3
(A) Time from first natalizumab infusion to confirmed EDSS progression in overall study population. (B) Time from first natalizumab infusion to confirmed EDSS improvement in patients with baseline EDSS scores ≥2.0. EDSS progression was defined as an increase, sustained for 6 months, of ≥0.5 points from a baseline EDSS score ≥6.0, of ≥1.0 point from a baseline EDSS score of ≥1.0 to
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Figure 3
Figure 3
(A) Time from first natalizumab infusion to confirmed EDSS progression in overall study population. (B) Time from first natalizumab infusion to confirmed EDSS improvement in patients with baseline EDSS scores ≥2.0. EDSS progression was defined as an increase, sustained for 6 months, of ≥0.5 points from a baseline EDSS score ≥6.0, of ≥1.0 point from a baseline EDSS score of ≥1.0 to

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