Learning ability correlates with brain atrophy and disability progression in RRMS.

To assess the prognostic value of practice effect on Paced Auditory Serial Addition Test (PASAT) in multiple sclerosis. We compared screening (day -14) and baseline (day 0) PASAT scores of 1009 patients from the FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) trial. We grouped patients into high and low learners if their PASAT score change was above or below the median change in their screening PASAT quartile group. We used Wilcoxon test to compare baseline disease characteristics between high and low learners, and multiple regression models to assess the respective impact of learning ability, baseline normalised brain volume and treatment on brain volume loss and 6-month confirmed disability progression over 2 years. The mean PASAT score at screening was 45.38, increasing on average by 3.18 from day -14 to day 0. High learners were younger (p=0.003), had lower Expanded Disability Status Scale score (p=0.031), higher brain volume (p<0.001) and lower T2 lesion volume (p=0.009) at baseline. Learning status was not significantly associated with disability progression (HR=0.953, p=0.779), when adjusting for baseline normalised brain volume, screening PASAT score and treatment arm. However, the effect of fingolimod on disability progression was more pronounced in high learners (HR=0.396, p<0.001) than in low learners (HR=0.798, p=0.351; p for interaction=0.05). Brain volume loss at month 24 tended to be higher in low learners (0.17%, p=0.058), after adjusting for the same covariates. Short-term practice effects on PASAT are related to brain volume, disease severity and age and have clinically meaningful prognostic implications. High learners benefited more from fingolimod treatment.

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Competing interests: This study was supported by Novartis Pharma AG, Basel, Switzerland. MPS received compensation for serving on the Scientific Advisory Boards of Teva, Genzyme, Novartis, Roche and Vertex; funding for travel or speaker honoraria from Merck Serono, Teva, Genzyme, Novartis, Biogen and Roche; consultancy from Merck Serono, Biogen, Teva, Genzyme, Roche, GeNeuro, MedDay and Novartis; Speakers' Bureaus from Teva, Merck Serono, Biogen, Novartis and Genzyme. NdS (University of Siena) has served on scientific advisory boards and steering committees of clinical trials for Merck Serono SA, Novartis Pharma AG and Teva, and has received support for congress participation or speaker honoraria from Bayer Schering AG, Biogen Idec, Merck Serono SA, Novartis Pharma AG, Sanofi-Aventis and Teva. GG has received compensation for serving as a consultant or speaker for or has received research support from AbbVie, Almirall, Atara Bio, Bayer Schering Healthcare, Biogen Idec, Canbex, Eisai, Elan, Five Prime Therapeutics, Genzyme, Genentech, GlaxoSmithKline, Ironwood Pharmaceuticals, Merck Serono, Novartis, Pfizer, Roche, Sanofi-Aventis, Synthon BV, Teva Pharmaceutical Industries, UCB and Vertex Pharmaceuticals. DL has participated on advisory boards/received consultancy/research grants or is in the Speaker Bureau for Bayer, Merck, Novartis, Teva, Excemed, Roche and Biogen. DP-M and DAH are employees of Novartis. LK has received no personal compensation. LK’s institution (University Hospital Basel) has received the following exclusively for research support: steering committee, advisory board and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB and Xenoport); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi and Teva); support for educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi and Teva); royalties (Neurostatus Products); licence fees for Neurostatus Products; and grants (Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society and Swiss National Research Foundation). DT is an employee of Novartis.