Efficacy Of Fingolimod In Pre-Treated Patients With Disease Activity: Pooled Analyses Of FREEDOMS and FREEDOMS II (P3.174)

Objective: Estimate the efficacy of fingolimod in patients with multiple sclerosis with evidence of high disease activity despite receiving treatment. Background: The efficacy of fingolimod has been assessed in two phase 3, placebo-controlled trials, FREEDOMS and FREEDOMS II. Methods: Post hoc analyses of clinical and magnetic resonance imaging (MRI) outcomes were performed in pooled subgroups of non-responder patients (as defined per EU label) from FREEDOMS and FREEDOMS II who had received treatment in the previous year and had: (subgroup 1) at least one relapse in the previous year and either at least one gadolinium-enhancing T1 lesion or at least nine T2 lesions at baseline or (subgroup 2) equal or more relapses in the year before baseline than in the previous year. Outcomes included annualized relapse rate (ARR), time to 3-month confirmed disability progression, percentage change from baseline in brain volume (BVL), number of gadolinium-enhancing T1 lesions, and number of new/newly enlarged T2 lesions. Results: ARRs were reduced by 55% for fingolimod 0.5 mg versus placebo in subgroup 1 and 50% in subgroup 2 (p<0.001). Fingolimod 0.5 mg reduced the risk of 3- and 6-month confirmed disability progression in patients in subgroup 2 by 34% (p=0.039) and 40% (p=0.042), respectively, compared with placebo. Similar reductions were observed in patients in subgroup 1. BVL was reduced by 45% (p<0.001) and 50% (p<0.001) versus placebo in subgroups 1 and 2, respectively. Reductions in gadolinium-enhancing T1 lesion counts for fingolimod 0.5 mg versus placebo were 68% (p<0.001) and 70% (p<0.001) in subgroups 1 and 2, respectively. Furthermore, in both subgroups, fingolimod 0.5 mg reduced new/newly enlarged T2 lesion count by 71% (p<0.001) over 24 months relative to placebo. Conclusions: Our analyses show that treatment with fingolimod in patients failing prior treatment is efficacious across all measures of disease activity, including disability progression. Study supported by: Novartis