Disability Progression in Multiple Sclerosis Patients in the Tysabri® (Natalizumab) Observational Program (TOP)

Background: TOP is an ongoing, open-label, 10-year prospective study of relapsing-remitting MS (RRMS) patients in clinical settings in Europe, Australia, Argentina, and Canada.

Objectives: To assess rates of disease progression in patients with RRMS treated with natalizumab for at least 2 years.

Methods: Patients with at least 2 years of data were evaluated for disability progression as assessed by ≥1.0-point and ≥2.0-point increases in EDSS score sustained for 6 months. Subgroup analyses investigated the percentage of patients with 6-month confirmed disability progression from baseline to EDSS scores of ≥3.0, ≥4.0, and ≥6.0.

Results: As of May 1, 2013, a total of 4821 patients were enrolled; 1080 of 3679 potential 2-year completers (29%) had discontinued treatment. Analyses included 2588 patients with available baseline EDSS scores who had completed at least 2 years in TOP. Patients received a median (range) of 35.5 (4-82) natalizumab infusions. Mean (standard deviation) baseline EDSS score in these patients was 3.4 (1.61). Overall, 303 patients (11.7%) had a ≥1.0-point increase in EDSS score and 88 patients (3.4%) had a ≥2.0-point increase sustained for 6 months. In subgroup analyses, 6-month confirmed EDSS progression to a score of ≥3.0 was seen in 54 of 698 patients (7.7%) with baseline scores of 0.0–2.0. Rates of confirmed EDSS progression to scores of ≥4.0 were 7.9% (98 of 1244) in patients with baseline scores of 0.0–3.0 and 12.3% (67 of 546) in patients with baseline scores of 2.0–3.0. Rates of confirmed EDSS progression to scores ≥6.0 were 2.7% (59 of 2167) in patients with baseline scores of 0.0–5.0 and 5.7% (53 of 923) in patients with baseline scores of 3.0–5.0. Progression rates among patients who discontinued treatment before and after 2 years will be examined, and analyses of 6-month and 12-month confirmed EDSS progression by subgroups determined by baseline EDSS scores and on-treatment relapse status will also be presented.

Conclusions: In this open-label observational setting, the low rate of progression to significant disability milestones, even among patients with greater disability at baseline, suggests a beneficial effect of natalizumab treatment on disability progression.