Contributions
Abstract: P1237
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Cognitive performance measured by Paced Auditory Serial Addition Test (PASAT) was shown to correlate with brain volume (BV), but is difficult to interpret longitudinally due to a practice effect. While BV loss (BVL) is increasingly recognized as predictor for disability progression, the association between learning ability (practice effect) with disease characteristics and long-term disease outcome is poorly investigated.
Objectives: To determine the correlation between practice effect and disease characteristics, and the relevance of practice effect and BV for future disability worsening and treatment impact.
Methods: In this posthoc analysis of data pooled from FREEDOMS and FREEDOMS II (n=1009, complete data set), practice effect was assessed by evaluating the change in PASAT score from screening (Day -14) to baseline (Day 0). High learners and low learners were defined as having a PASAT score change above or below the median of their screening PASAT quartile group. A multiple regression model was used to evaluate the correlation between practice effect and baseline disease characteristics, and a Cox regression hazard model to assess the impact of learning ability, baseline normalised BV (NBV) and treatment on BVL and 3-month confirmed disability progression (CDP) over 2 years.
Results: Mean screening PASAT score was 45.4, increasing on average by 3.2 from Day -14 to Day 0; change ranged from 5.0 (Q1) to 0.5 (Q4). Higher learners had higher NBV (p< 0.001), lower clinical and MRI disease burden (EDSS, p=0.031; T2LV, p=0.009) and younger age (p=0.003) at baseline. NBV was correlated with CDP (HR 0.758, p=0.006) but PASAT Day -14 (HR 0.990, p=0.151) or PASAT change (HR 0.953, p=0.779) did not correlate with CDP when adjusted for NBV. Fingolimod had an effect on BVL (difference 0.39%, p< 0.001), with low learners experiencing greater BVL at Month 24 than high learners (difference 0.17%, p=0.058). There was an effect of fingolimod on disability progression (HR 0.561, p=0.001), which was greater in high learners (HR 0.396, p< 0.001) than in low learners (HR 0.798, p=0.351), p for interaction=0.05.
Conclusions: The data suggest that short-term changes in PASAT are of clinical relevance and depend on NBV, disease severity and age. High learners had a lower rate of BVL and benefited more from treatment than low learners, supporting the early implementation of efficient treatment strategies that slow BVL for a favorable long-term prognosis.
Disclosure: Dawn W Langdon has participated on advisory boards/received consultancy/research grants or is in the speaker Bureau for: Bayer, Novartis, and Teva, Excemed, Roche, and Biogen.
Ludwig Kappos´s institution has received in the last 3 years and used exclusively for research support: steering committee, advisory board, consultancy or speaker fees, or support of educational activities from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport, and CSL Behring; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
Maria Pia Sormani has received compensation for consulting services and speaking activities from Actelion, Biogen Idec, Genzyme, Merck Serono, Novartis, Synthon and Teva.
Gavin Giovannoni has received compensation for serving as a consultant or speaker for, or has received research support from: AbbVie, 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.
Nicola De Stefano 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
Daniela Piani Meier, Dieter A Häring, Davorka Tomic are employee of Novartis
Abstract: P1237
Type: Poster
Abstract Category: Therapy - disease modifying - Long-term treatment monitoring
Background: Cognitive performance measured by Paced Auditory Serial Addition Test (PASAT) was shown to correlate with brain volume (BV), but is difficult to interpret longitudinally due to a practice effect. While BV loss (BVL) is increasingly recognized as predictor for disability progression, the association between learning ability (practice effect) with disease characteristics and long-term disease outcome is poorly investigated.
Objectives: To determine the correlation between practice effect and disease characteristics, and the relevance of practice effect and BV for future disability worsening and treatment impact.
Methods: In this posthoc analysis of data pooled from FREEDOMS and FREEDOMS II (n=1009, complete data set), practice effect was assessed by evaluating the change in PASAT score from screening (Day -14) to baseline (Day 0). High learners and low learners were defined as having a PASAT score change above or below the median of their screening PASAT quartile group. A multiple regression model was used to evaluate the correlation between practice effect and baseline disease characteristics, and a Cox regression hazard model to assess the impact of learning ability, baseline normalised BV (NBV) and treatment on BVL and 3-month confirmed disability progression (CDP) over 2 years.
Results: Mean screening PASAT score was 45.4, increasing on average by 3.2 from Day -14 to Day 0; change ranged from 5.0 (Q1) to 0.5 (Q4). Higher learners had higher NBV (p< 0.001), lower clinical and MRI disease burden (EDSS, p=0.031; T2LV, p=0.009) and younger age (p=0.003) at baseline. NBV was correlated with CDP (HR 0.758, p=0.006) but PASAT Day -14 (HR 0.990, p=0.151) or PASAT change (HR 0.953, p=0.779) did not correlate with CDP when adjusted for NBV. Fingolimod had an effect on BVL (difference 0.39%, p< 0.001), with low learners experiencing greater BVL at Month 24 than high learners (difference 0.17%, p=0.058). There was an effect of fingolimod on disability progression (HR 0.561, p=0.001), which was greater in high learners (HR 0.396, p< 0.001) than in low learners (HR 0.798, p=0.351), p for interaction=0.05.
Conclusions: The data suggest that short-term changes in PASAT are of clinical relevance and depend on NBV, disease severity and age. High learners had a lower rate of BVL and benefited more from treatment than low learners, supporting the early implementation of efficient treatment strategies that slow BVL for a favorable long-term prognosis.
Disclosure: Dawn W Langdon has participated on advisory boards/received consultancy/research grants or is in the speaker Bureau for: Bayer, Novartis, and Teva, Excemed, Roche, and Biogen.
Ludwig Kappos´s institution has received in the last 3 years and used exclusively for research support: steering committee, advisory board, consultancy or speaker fees, or support of educational activities from Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, Xenoport, and CSL Behring; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen Idec, European Union, Merck, Novartis, Roche Research Foundation, Swiss MS Society, and the Swiss National Research Foundation.
Maria Pia Sormani has received compensation for consulting services and speaking activities from Actelion, Biogen Idec, Genzyme, Merck Serono, Novartis, Synthon and Teva.
Gavin Giovannoni has received compensation for serving as a consultant or speaker for, or has received research support from: AbbVie, 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.
Nicola De Stefano 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
Daniela Piani Meier, Dieter A Häring, Davorka Tomic are employee of Novartis