The effect of fingolimod on T1-hypointense lesions developed on-study and evolution of pre-existing Gd+ lesions, stratified by lesion size: A posthoc analysis of FREEDOMS study (P7.245)

Objectives: To evaluate fingolimod-effects on: 1) T1-hypointense lesions (T1HL) that developed on-study and 2) evolution of baseline Gd + -lesions, stratified by average size, into new T1HL. Background: In the 2-year FREEDOMS study, fingolimod 0.5mg significantly reduced the proportion of baseline Gd + -lesions evolving into T1HL and the [percnt] of patients developing T1HL. Published literature suggests larger Gd + -lesions are more likely to become T1HL (MacManus et al, J Neurol (2011) 258:449-456). Methods: 1) T1HL that developed on-study were counted in all patients (irrespective if they had Gd + -lesions at baseline or not) and analyzed in a negative-binomial model. 2) Baseline Gd + -lesions were followed at Months (M) 6, 12 and 24. Gd + -patients at baseline were stratified by their average Gd + -lesion volume at baseline (total volume/lesion count) into subgroups: low-volume (LV; n=236) and high-volume (HV; n=246) with means below or above the median (74.4mm 3 ). A logistic-regression model, adjusted for treatment and number of Gd + -lesions at screening was used to analyze evolution of above- and below-average volume Gd + -lesions into T1-hypointense lesions, for fingolimod vs. placebo. Results: Overall, irrespective of Gd + -status at baseline, the mean numbers of newly-developed, T1HL over 24-months were 1.0 and 2.5 (p + -lesions in fingolimod-treated patients in the HV-subgroup were less likely to evolve into T1HL compared with placebo [(M6:46[percnt] vs. 62[percnt];p=0.071); (M12:33[percnt] vs. 55[percnt];p=0.005);(M24:32[percnt] vs. 48[percnt];p=0.011)]. In the LV-subgroup, fewer Gd + -lesions evolved into T1HL, with no clear treatment effect. Patient-level analysis will be presented at the meeting. Conclusions: In the FREEDOMS population, HV-lesions were more likely than LV-lesions to evolve into T1HL. Fingolimod decreased the overall number of T1HL that developed on-study and reduced the risk of high-volume Gd + -lesions to evolve into T1HL. Study supported by: Novartis Pharma AG. Disclosure: Dr. Sprenger9s institution has received research support from Novartis, ElectroCore, Genzyme, Actelion, Mitsubishi Pharma Europe, and Biogen Idec. Dr. Radu has received personal compensation for activities with Actelion, Basilea Pharmaceutica, Bayer Schering, Biogen Idec, Merck Serono, and Novartis. Dr. Mueller-Lenke has received personal compensation for activities with Biogen Idec, Merck-Serono, and Novartis as a consultant and/or speaker. Dr. Mueller-Lenke has received research support from Biogen Idec, Merck-Serono, and Novartis. Dr. Francis has received personal compensation for activities with Novartis as an employee. Dr. Haering 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.