Contributions
Abstract: P497
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Limited data are available on the ability of magnetic resonance imaging (MRI) parameters to predict cognitive changes or improvements in physical ability in multiple sclerosis (MS).
Objectives: Assess the predictive value of MRI parameters for physical and cognitive outcomes in MS at ≤8 years.
Methods: Post hoc analyses of data from patients with relapsing MS on fingolimod in the placebo-controlled, phase 3 FREEDOMS and FREEDOMS II trials and their extensions. Baseline (BL) MRI predictors analysed included T1 hypointense lesion volume (T1LV), T2 lesion volume (T2LV), presence of gadolinium-enhancing (Gd+) lesions and normalized brain volume (NBV). Other predictors included new T2 lesions, change in T2LV and annualized rate of brain atrophy (ARBA), all from BL to months 12 (M12) or 24 (M24), and change in T1LV from BL to M24. Outcomes were transition to secondary progressive MS (SPMS), confirmed disability improvement (CDI; a decrease in Expanded Disability Status Scale score of 1.0 or 0.5 points, if baseline score ≤5.5 or ≥6.0, respectively, confirmed at 6 months), CDI+ (CDI or improvement of ≥20% in 9-hole peg or timed 25-foot walk tests, confirmed at 6 months) and cognitive worsening (a decrease of ≥20% in the paced auditory serial addition test confirmed at 6 months). Predictors were categorized by quartile, except for Gd+ and new T2 lesions, which were dichotomized by presence/absence. Baseline-adjusted Cox proportional hazards model compared risk of worst vs best category; log-rank test determined predictive value of MRI parameters.
Results: For CDI and CDI+, the only significant predictors were baseline NBV and T1LV: low NBV (hazard ratio [HR]: 0.59 and 0.63; p< 0.01) and high T1LV (HR: 0.56 and 0.73; p< 0.05) predicted less CDI and CDI+, respectively. High baseline T1LV and T2LV predicted increased SPMS risk (HR: 2.88 and 2.83; p< 0.01), as did greater change in T1LV at M24 (HR: 2.32; p< 0.05). Risk of cognitive worsening correlated with high baseline T1LV and T2LV (HR: 3.00 and 2.51, respectively; p< 0.01), low NBV (HR: 3.51; p< 0.001), high ARBA at M12 (HR: 1.87; p< 0.05) and high Gd+ lesions (HR: 1.9; p< 0.01). By log-rank test, NBV was significantly predictive of all parameters tested (p< 0.001); T1LV was the second most robust parameter (p< 0.01 for all except CDI+).
Conclusions: Overall, disease burden measures, particularly NBV, are more robust prognostic parameters of long-term disease progression than MRI lesion activity.
Disclosure: Douglas Jeffery has received honoraria as a speaker and consultant from Acorda, Bayer, Biogen, Genzyme, Glaxo, Novartis, Pfizer, Questcor, Serono and Teva; and research support from Bayer, Biogen, Genzyme, Novartis, Pfizer, Serono and Teva. Dieter A. Häring, Daniela Piani Meier, and Davorka Tomic are employees of Novartis Pharma AG.
Abstract: P497
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Limited data are available on the ability of magnetic resonance imaging (MRI) parameters to predict cognitive changes or improvements in physical ability in multiple sclerosis (MS).
Objectives: Assess the predictive value of MRI parameters for physical and cognitive outcomes in MS at ≤8 years.
Methods: Post hoc analyses of data from patients with relapsing MS on fingolimod in the placebo-controlled, phase 3 FREEDOMS and FREEDOMS II trials and their extensions. Baseline (BL) MRI predictors analysed included T1 hypointense lesion volume (T1LV), T2 lesion volume (T2LV), presence of gadolinium-enhancing (Gd+) lesions and normalized brain volume (NBV). Other predictors included new T2 lesions, change in T2LV and annualized rate of brain atrophy (ARBA), all from BL to months 12 (M12) or 24 (M24), and change in T1LV from BL to M24. Outcomes were transition to secondary progressive MS (SPMS), confirmed disability improvement (CDI; a decrease in Expanded Disability Status Scale score of 1.0 or 0.5 points, if baseline score ≤5.5 or ≥6.0, respectively, confirmed at 6 months), CDI+ (CDI or improvement of ≥20% in 9-hole peg or timed 25-foot walk tests, confirmed at 6 months) and cognitive worsening (a decrease of ≥20% in the paced auditory serial addition test confirmed at 6 months). Predictors were categorized by quartile, except for Gd+ and new T2 lesions, which were dichotomized by presence/absence. Baseline-adjusted Cox proportional hazards model compared risk of worst vs best category; log-rank test determined predictive value of MRI parameters.
Results: For CDI and CDI+, the only significant predictors were baseline NBV and T1LV: low NBV (hazard ratio [HR]: 0.59 and 0.63; p< 0.01) and high T1LV (HR: 0.56 and 0.73; p< 0.05) predicted less CDI and CDI+, respectively. High baseline T1LV and T2LV predicted increased SPMS risk (HR: 2.88 and 2.83; p< 0.01), as did greater change in T1LV at M24 (HR: 2.32; p< 0.05). Risk of cognitive worsening correlated with high baseline T1LV and T2LV (HR: 3.00 and 2.51, respectively; p< 0.01), low NBV (HR: 3.51; p< 0.001), high ARBA at M12 (HR: 1.87; p< 0.05) and high Gd+ lesions (HR: 1.9; p< 0.01). By log-rank test, NBV was significantly predictive of all parameters tested (p< 0.001); T1LV was the second most robust parameter (p< 0.01 for all except CDI+).
Conclusions: Overall, disease burden measures, particularly NBV, are more robust prognostic parameters of long-term disease progression than MRI lesion activity.
Disclosure: Douglas Jeffery has received honoraria as a speaker and consultant from Acorda, Bayer, Biogen, Genzyme, Glaxo, Novartis, Pfizer, Questcor, Serono and Teva; and research support from Bayer, Biogen, Genzyme, Novartis, Pfizer, Serono and Teva. Dieter A. Häring, Daniela Piani Meier, and Davorka Tomic are employees of Novartis Pharma AG.