Contributions
Abstract: P1064
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Inflammatory-demyelinating lesions in the central nervous system (CNS) are the hallmark of MS. Although they are disseminated throughout the CNS, there is a predilection of certain areas (e.g. periventricular region). Apart from lesion load, lesion location is thought to be an important predictor of MS disability.
Objective: To quantify regional T2-weighted (T2w) lesion occurrence and likelihood of new/enlarging (n/e) T2w lesion formation in different brain regions in a large longitudinal dataset of RRMS patients and to assess the regional homogeneity of fingolimod treatment effects on lesion formation.
Methods: Baseline (BL) and Month 24 (M24) data of 2355 RRMS patients from FREEDOMS and FREEDOMS II clinical trials were coregistered to standard space and, if this step was successful, included in the study (regardless of MRI activity). BL T2w and M24 n/e T2w lesion numbers were computed in 11 anatomical regions based on the Talairach atlas (supratentorial: frontal, sub-lobar, limbic, temporal, parietal, occipital lobe; infratentorial: anterior and posterior lobe of cerebellum, pons, midbrain, medulla). For each region, M24 n/e lesion number was analysed using a negative binomial regression with treatment, clinical trial and BL lesion number as covariates.
Results: Overall, 1351 (placebo, 446; fingolimod, 905) patients were included in the analysis. BL characteristics (female, 72.5%; age [mean±SD], 38.3±8.8 years; disease duration, 8.9±7.2 years; EDSS score, 2.4±1.3) were balanced between treatment arms and were consistent with the overall population of the pooled trials. At BL, 99% of the total T2w lesions were located supratentorially (35.7% frontal; 20.5% sub-lobar; 14.3% temporal; 11.6% limbic; 10.5% parietal; 6.4% occipital). At M24, the n/e T2w lesions in the placebo group were 13.7±17 and mainly occurred supratentorially (frontal, 4.04±5.39; sub-lobar, 3.05±3.85; limbic, 2.32±3.09; temporal, 1.80±2.57; parietal, 1.33±1.88; occipital, 0.72±1.16). Fingolimod reduced the n/e T2w lesions by 73% (p< 0.0001; 95% CI: 0.22, 0.33); reductions ranging from 69% (sub-lobar) — 76% (temporal) supratentorially, and 53% (midbrain) — 84% (medulla) infratentorially. The reduction of n/e T2w lesions in the entire brain was significant compared with placebo; no evidence of heterogeneity across locations was detected.
Conclusions: New T2w lesions mainly form supratentorially and fingolimod treatment reduced the occurrence of n/e T2w lesions throughout the brain.
Disclosure: Funding source: This study has been funded by Novartis Pharma AG.
Anna Altermatt has nothing to disclose.
Stefano Magon received research support from Swiss MS Society, Swiss National Science Foundation, University of Basel and Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie
der medizinischen Bildauswertung Universitätsspital Basel.
Nicole Müller-Lenke has nothing to disclose.
Ernst-Wilhelm Radue has received research support from Actelion, Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, and Sanofi.
Jens Wuerfel is CEO of MIAC AG. He served on advisory boards for Actelion, Biogen, Genzyme, Novartis and Roche. He received research grants from Novartis, and speaker honoraria from Bayer, Biogen, Genzyme, Novartis, Teva and Biogen. JW was supported by the DFG, the EU, the German ministry of education and research (BMBF/KKNMS) and the German ministry of economy (BMWi).
Ludwig Kappos has received no personal compensation. In the last 3 years, Ludwig Kappos' 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 of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva); royalties (Neurostatus products); license 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).
Till Sprenger has received no personal compensation. The current of previous employers of TS have received compensation from Biogen Idec, Eli Lilly, Allergan, Actelion, ATI, Mitsubishi Pharma, Novartis, TEVA and Sanofi Genzyme. Dr. Sprenger received research support from Novartis Pharmaceuticals Switzerland, the Swiss MS Society, and Swiss National Science Foundation.
Laura Gaetano, Baldur Magnusson, Davorka Tomic, Diego Silva and Dieter A. Häring are employees of Novartis.
Abstract: P1064
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: Inflammatory-demyelinating lesions in the central nervous system (CNS) are the hallmark of MS. Although they are disseminated throughout the CNS, there is a predilection of certain areas (e.g. periventricular region). Apart from lesion load, lesion location is thought to be an important predictor of MS disability.
Objective: To quantify regional T2-weighted (T2w) lesion occurrence and likelihood of new/enlarging (n/e) T2w lesion formation in different brain regions in a large longitudinal dataset of RRMS patients and to assess the regional homogeneity of fingolimod treatment effects on lesion formation.
Methods: Baseline (BL) and Month 24 (M24) data of 2355 RRMS patients from FREEDOMS and FREEDOMS II clinical trials were coregistered to standard space and, if this step was successful, included in the study (regardless of MRI activity). BL T2w and M24 n/e T2w lesion numbers were computed in 11 anatomical regions based on the Talairach atlas (supratentorial: frontal, sub-lobar, limbic, temporal, parietal, occipital lobe; infratentorial: anterior and posterior lobe of cerebellum, pons, midbrain, medulla). For each region, M24 n/e lesion number was analysed using a negative binomial regression with treatment, clinical trial and BL lesion number as covariates.
Results: Overall, 1351 (placebo, 446; fingolimod, 905) patients were included in the analysis. BL characteristics (female, 72.5%; age [mean±SD], 38.3±8.8 years; disease duration, 8.9±7.2 years; EDSS score, 2.4±1.3) were balanced between treatment arms and were consistent with the overall population of the pooled trials. At BL, 99% of the total T2w lesions were located supratentorially (35.7% frontal; 20.5% sub-lobar; 14.3% temporal; 11.6% limbic; 10.5% parietal; 6.4% occipital). At M24, the n/e T2w lesions in the placebo group were 13.7±17 and mainly occurred supratentorially (frontal, 4.04±5.39; sub-lobar, 3.05±3.85; limbic, 2.32±3.09; temporal, 1.80±2.57; parietal, 1.33±1.88; occipital, 0.72±1.16). Fingolimod reduced the n/e T2w lesions by 73% (p< 0.0001; 95% CI: 0.22, 0.33); reductions ranging from 69% (sub-lobar) — 76% (temporal) supratentorially, and 53% (midbrain) — 84% (medulla) infratentorially. The reduction of n/e T2w lesions in the entire brain was significant compared with placebo; no evidence of heterogeneity across locations was detected.
Conclusions: New T2w lesions mainly form supratentorially and fingolimod treatment reduced the occurrence of n/e T2w lesions throughout the brain.
Disclosure: Funding source: This study has been funded by Novartis Pharma AG.
Anna Altermatt has nothing to disclose.
Stefano Magon received research support from Swiss MS Society, Swiss National Science Foundation, University of Basel and Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie
der medizinischen Bildauswertung Universitätsspital Basel.
Nicole Müller-Lenke has nothing to disclose.
Ernst-Wilhelm Radue has received research support from Actelion, Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, and Sanofi.
Jens Wuerfel is CEO of MIAC AG. He served on advisory boards for Actelion, Biogen, Genzyme, Novartis and Roche. He received research grants from Novartis, and speaker honoraria from Bayer, Biogen, Genzyme, Novartis, Teva and Biogen. JW was supported by the DFG, the EU, the German ministry of education and research (BMBF/KKNMS) and the German ministry of economy (BMWi).
Ludwig Kappos has received no personal compensation. In the last 3 years, Ludwig Kappos' 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 of educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, and Teva); royalties (Neurostatus products); license 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).
Till Sprenger has received no personal compensation. The current of previous employers of TS have received compensation from Biogen Idec, Eli Lilly, Allergan, Actelion, ATI, Mitsubishi Pharma, Novartis, TEVA and Sanofi Genzyme. Dr. Sprenger received research support from Novartis Pharmaceuticals Switzerland, the Swiss MS Society, and Swiss National Science Foundation.
Laura Gaetano, Baldur Magnusson, Davorka Tomic, Diego Silva and Dieter A. Häring are employees of Novartis.