Dawn W Langdon1, Davorka Tomic2, Iris-Katharina Penner3,4, Pasquale Calabrese5, Gary Cutter6, Dieter A Häring2, Frank Dahlke2, Ludwig Kappos7. 1. Department of Psychology, Royal Holloway, University of London, Egham, UK. 2. Novartis Pharma AG, Basel, Switzerland. 3. Medical Faculty, Department of Neurology, Heinrich Heine University, Düsseldorf, Germany. 4. COGITO Center for Applied Neurocognition and Neuropsychological Research, Düsseldorf, Germany. 5. Neuropsychology and Behavioral Neurology Unit, Division of Cognitive and Molecular Neuroscience, University of Basel, Switzerland. 6. Department of Biostatistics, University of Alabama, Birmingham, AL, USA. 7. Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) and MS Center, Neurology, Departments of Head, Spine and Neuromedicine and Clinical Research, University Hospital and University of Basel, Spitalstrasse 2, Basel, Schweiz, 4031, Switzerland.
Abstract
BACKGROUND AND PURPOSE: Studies reporting the baseline determinants of cognitive performance and treatment effect on cognition in patients with multiple sclerosis (MS) are limited. We investigated the baseline correlates of cognition and the long-term treatment effects of fingolimod 0.5 mg once daily on cognitive processing speed and attention in patients with relapsing-remitting MS. METHODS: This post hoc analysis pooled data from the phase 3 FREEDOMS and FREEDOMS II trials (N = 1556). We assessed the correlation between baseline patient demographic and disease characteristics and baseline 3-second Paced Auditory Serial Addition Test (PASAT-3) scores (Spearman's rank test) and the changes from baseline in PASAT-3 (mixed model repeated measures model) in the fingolimod and placebo (up to 24 months) or placebo-fingolimod switched (from Month 24 up to 120 months) groups. Additionally, the predictive value of PASAT-3 score for future disease outcomes was assessed (Cox or logistic regression models). RESULTS: Among the variables assessed, lower PASAT-3 score at baseline correlated with higher disease burden (total brain volume, T2 lesion volume, and Expanded Disability Status Scale score), longer disease duration and older age (p < 0.0001 for all). Fingolimod significantly improved PASAT-3 scores from baseline versus placebo at 6 (1.3; p = 0.0007), 12 (1.1; p = 0.0044) and 24 months (1.1; p = 0.0028), with a sustained effect (overall treatment effect p = 0.0012) up to 120 months. Improvements were seen regardless of baseline cognitive status (PASAT quartile). Baseline PASAT-3 score was predictive of both clinical and magnetic resonance imaging measures of disease activity at Month 24 (p < 0.001 for all). CONCLUSION: Early fingolimod treatment may offer long-term cognitive benefit in patients with relapsing-remitting MS.
BACKGROUND AND PURPOSE: Studies reporting the baseline determinants of cognitive performance and treatment effect on cognition in patients with multiple sclerosis (MS) are limited. We investigated the baseline correlates of cognition and the long-term treatment effects of fingolimod 0.5 mg once daily on cognitive processing speed and attention in patients with relapsing-remitting MS. METHODS: This post hoc analysis pooled data from the phase 3 FREEDOMS and FREEDOMS II trials (N = 1556). We assessed the correlation between baseline patient demographic and disease characteristics and baseline 3-second Paced Auditory Serial Addition Test (PASAT-3) scores (Spearman's rank test) and the changes from baseline in PASAT-3 (mixed model repeated measures model) in the fingolimod and placebo (up to 24 months) or placebo-fingolimod switched (from Month 24 up to 120 months) groups. Additionally, the predictive value of PASAT-3 score for future disease outcomes was assessed (Cox or logistic regression models). RESULTS: Among the variables assessed, lower PASAT-3 score at baseline correlated with higher disease burden (total brain volume, T2 lesion volume, and Expanded Disability Status Scale score), longer disease duration and older age (p < 0.0001 for all). Fingolimod significantly improved PASAT-3 scores from baseline versus placebo at 6 (1.3; p = 0.0007), 12 (1.1; p = 0.0044) and 24 months (1.1; p = 0.0028), with a sustained effect (overall treatment effect p = 0.0012) up to 120 months. Improvements were seen regardless of baseline cognitive status (PASAT quartile). Baseline PASAT-3 score was predictive of both clinical and magnetic resonance imaging measures of disease activity at Month 24 (p < 0.001 for all). CONCLUSION: Early fingolimod treatment may offer long-term cognitive benefit in patients with relapsing-remitting MS.
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Authors: Dawn W Langdon; Davorka Tomic; Iris-Katharina Penner; Pasquale Calabrese; Gary Cutter; Dieter A Häring; Frank Dahlke; Ludwig Kappos Journal: Eur J Neurol Date: 2021-10-12 Impact factor: 6.288
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