Impact of fingolimod on achieving no evidence of disease activity and worsening (NEDA)-4 in previously treated patients with high disease activity (P3.246)

OBJECTIVE: To estimate differences between fingolimod and placebo on achieving no evidence of disease activity (NEDA) status in patients with relapsing remitting multiple sclerosis (RRMS) who had high disease activity before the study despite prior use of disease-modifying therapy (DMT). BACKGROUND: Disease activity and worsening in RRMS are driven by both focal and diffuse damage. In clinical trials, the NEDA concept usually considers active MRI lesions, relapses, and disability progression. Addition of brain volume loss (BVL), as an objective measure of global tissue damage, to NEDA was recently suggested (NEDA-4). BVL inclusion should yield a more comprehensive and balanced measure of activity and worsening in RRMS. DESIGN/METHODS: Post-hoc pooled analysis of FREEDOMS and FREEDOMS II was performed for previously treated patients who had high disease activity despite DMT in the past year (equal or more relapses in the year before the study than in the previous year or 蠅1 relapse in the year before the study and 蠅1 Gd+ lesions or 蠅9 T2 lesions at baseline. NEDA-4 definition: absence of confirmed relapses, 6-month confirmed disability progression, new/enlarging T2 lesions and BVL (annual percent brain volume loss [PBVL]) of less than 0.4[percnt]. RESULTS: Over two years, fingolimod-treated patients were more likely (p -0.2[percnt]): 17.4[percnt] vs 3.5[percnt]; 5.83; 2.65-12.80 or accelerated BVL (>-1.2[percnt]): 28.5[percnt] vs 8.3[percnt]; 4.41; 2.53-7.68; p<0.0001 for both. CONCLUSIONS: In patients who had high disease activity despite DMT use within the year before the study, those treated with fingolimod were 4-6 times more likely to achieve NEDA-4 than those receiving placebo. Study supported by Novartis Pharma AG. Disclosure: Dr. De Stefano has received personal compensation for activities with Teva Neuroscience, Bayer, Sanofi-Aventis, Biogen Idec, Novartis, and Merck Serono. Dr. Sprenger9s institution has received research support from Novartis, ElectroCore, Genzyme, Actelion, Mitsubishi Pharma Europe, and Biogen Idec. Dr. Sormani has received personal compensation for activities with Allozyne, Merck Serono, Teva Neuroscience, Synthon, Actelion, and Biogen Idec as a consultant and/or speaker. Dr. Havrdova has received research support from the Czech Ministries of Education and Health. Dr. Radu has received personal compensation for activities with Actelion, Basilea Pharmaceutica, Bayer Schering, Biogen Idec, Merck Serono, and Novartis. Dr. Bergvall has received personal compensation for activities with Novartis as an employee. Dr. Meier has received personal compensation for activities with Novartis as an employee. Dr. Tomic has received personal compensation for activities with Novartis as an employee. Dr. Kappos has received personal compensation for activities with Actelion Pharmaceuticals.