Epoch Analysis of On-Treatment Disability Progression Events over Time in the Tysabri Observational Program (TOP)

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 p p p 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.