Natalizumab Reduces Total Disability Burden Relative to Placebo in Patients with Relapsing-Remitting Multiple Sclerosis Regardless of the Occurrence of Relapses or Confirmed Disability Progression or Improvement over 2 Years in the AFFIRM Study (P7.244)

OBJECTIVE: To quantify natalizumab’s treatment effect on disability over 2 years using an area-under-the-curve (AUC) analysis of Expanded Disability Status Scale (EDSS) scores in subgroups of relapsing-remitting multiple sclerosis patients in the phase 3 placebo-controlled AFFIRM study. BACKGROUND: Previous AUC analyses integrating repeated measures of all EDSS changes in AFFIRM patients showed net disability improvement with natalizumab (n=627) and net worsening with placebo (n=315). DESIGN/METHODS: AUC change in EDSS (expressed in EDSS-years) was calculated using EDSS assessments every 3 months. Positive AUC changes indicate net EDSS worsening; negative changes indicate net improvement. Patients were categorized by relapse status (0 or 蠅1 relapse) and by confirmed (3-month and 6-month) disability progression status (as progressors/nonprogressors) or improvement status (as improvers/nonimprovers). Progression and improvement were defined as a 蠅1.0-point increase or decrease from baseline EDSS score, respectively. Within each subgroup, mean AUC change was compared between treatment groups. RESULTS: Among patients with no relapses, net improvement in disability was greater with natalizumab than with placebo (difference: -0.21 EDSS-years; P =0.044). In patients with 蠅1 relapse, net worsening in disability occurred in both treatment groups but was numerically lower with natalizumab (difference: -0.31 EDSS-years; P =0.057). Findings were similar among progressors, with a positive AUC change of approximately 2 EDSS years (difference between treatment groups: -0.33 [ P =0.036] and -0.21 [ P =0.210] EDSS-years for 3-month and 6-month criteria, respectively). Nonprogressors had negative AUC changes in EDSS, with greater net improvement with natalizumab than with placebo (difference in EDSS-years: -0.25 [ P =0.001] and -0.22 [ P =0.006] for 3-month and 6-month criteria, respectively). AUC changes in improvers and nonimprovers will also be presented. CONCLUSIONS: Analysis of AUC change in EDSS revealed that natalizumab has significant effects on total disability burden among relapse-free patients and highly significant effects among nonprogressors that conventional, categorical EDSS outcome measures failed to capture. Study supported by: Biogen Idec. Disclosure: Dr. Gioannoni has received personal compensation for activities with AbbVie as a steering committee member. Dr. Belachew has received personal compensation for activities with Biogen Idec as an employee. Dr. Dong has received personal compensation for activities with Biogen Idec as an employee. Dr. Rudick has received personal compensation for activities with Biogen Idec as an employee. Dr. Mikol has received personal compensation for activities with Biogen Idec as an employee. Dr. Shang has nothing to disclose.