Abstract
ObjectiveTo evaluate the effect of natalizumab on disability progression beyond 2 years of treatment in clinical practice.MethodsAnalyses included the 496 relapsing-remitting multiple sclerosis (RRMS) patients among 5122 patients in the Tysabri Observational Program (TOP) who had completed 4 continuous years of natalizumab treatment and had baseline (study enrollment) and postbaseline Expanded Disability Status Scale (EDSS) assessments. Proportions of patients with 6-month or 12-month confirmed ≥1.0-point EDSS progression relative to baseline were compared in treatment months 1–24 and 25–48. Sensitivity analyses compared progression rates in months 13–24 and 25–36.ResultsBaseline characteristics appeared similar between the overall TOP population (N = 5122), patients who had completed 4 years of natalizumab treatment (n = 469), and patients eligible to complete 4 years in TOP who had discontinued natalizumab after 2 years of treatment (n = 514). Among 4-year completers, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased between months 1–24 and 25–48 of natalizumab treatment by 42% (from 10.9% to 6.3%; p < 0.01) and 52% (from 9.5% to 4.6%; p < 0.01), respectively. Few patients had 6-month or 12-month confirmed EDSS progression in both epochs (0.6% and 0.2%, respectively). Between months 13–24 and 25–36 of treatment, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased by 60% (from 7.5% to 3.0%; p < 0.01) and 58% (from 6.7% to 2.8%; p < 0.01), respectively. Significant reductions in disability progression events between months 13–24 and 25–36 were also observed in relapse-free patients.ConclusionIn this observational study, the disability progression rate decreased further beyond 2 years of natalizumab treatment. Patients who responded well and remained on continuous natalizumab therapy for over 4 years had sustained and potentially enhanced reductions in EDSS progression over time.
Highlights
In the phase 3 natalizumab safety and efficacy in relapsing-remitting multiple sclerosis (RRMS) clinical trial (AFFIRM), natalizumab reduced the risk of 3-month and 6-month confirmed disability progression over 2 years by 42% and 54%, respectively, compared with placebo [1]
Among 4-year completers, the proportion of patients with 6-month and 12-month confirmed Expanded Disability Status Scale (EDSS) progression decreased between months 1–24 and 25–48 of natalizumab treatment by 42% and 52%, respectively
The cumulative probability of 6-month confirmed EDSS progression in the first 2 years of Tysabri (natalizumab) Observational Program (TOP) appeared higher in those patients who discontinued due to reported lack of efficacy (Kaplan-Meier [KM] estimate = 22%) than in either the 4-year completer population (KM estimate = 11%) or patients who discontinued for reasons other than lack of efficacy (KM estimate = 10%)
Summary
In the phase 3 natalizumab safety and efficacy in relapsing-remitting multiple sclerosis (RRMS) clinical trial (AFFIRM), natalizumab reduced the risk of 3-month and 6-month confirmed disability progression over 2 years by 42% and 54%, respectively, compared with placebo [1]. The 10-year, prospective Tysabri (natalizumab) Observational Program (TOP; NCT00493298) was established to report the long-term safety and efficacy of natalizumab for the treatment of RRMS in a clinical practice setting. In a post hoc multiple-event analysis of TOP EDSS data, we tested the hypothesis that the effect of natalizumab on disability progression could change over time, in particular beyond 2 years, by comparing the rate of confirmed EDSS progression events in the same patient population across treatment epochs ranging up to 4 years
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