Contributions
Abstract: P812
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: No longitudinal studies in multiple sclerosis (MS) examined the effect of fingolimod on development of thalamic pathology, progression of cognitive impairment, and their association with evolution of environmental risk factors.
Objectives: To assess the effect of fingolimod on thalamic pathology (as measured by volume and susceptibility changes), cognitive deterioration and humoral response to Epstein-Barr virus (EBV) over 24 months in patients with relapsing MS.
Methods: This was a prospective, observational, single-blinded study of 20 relapsing MS patients starting treatment with fingolimod, and 20 age- and sex-matched healthy controls (HCs). Subjects were assessed at baseline, 6, 12, and 24 months with clinical, cognitive, MRI, and humoral response to EBV examinations. MRI outcomes included thalamic volume and susceptibility measurements from baseline to 24 months. Baseline group effect differences (MS vs. HCs) were investigated using analysis of covariance analysis adjusted for age and sex. The differences over time, between MS and HCs, were investigated by using interaction effect of group by time (RM-ANCOVA).
Results: MS patients remained clinically stable over 24 months. There were no significant differences between MS and HCs in cognitive or EBV changes over 24 months. At baseline, MS patients had lower thalamic volume (p< 0.001) and susceptibility (p=0.003) compared to HCs. Over the follow-up, no significant differences in thalamic volume changes were found between MS patients and HCs. However, there was a significant reduction in thalamic susceptibility between MS and HCs, which was significant at 0-6 months (p=0.002), 6-12 months (p=0.042) and 0-12 months (p=0.042), but not 0-24 months (p=0.185).
Conclusions: This 24-month study showed stability of clinical, cognitive, EBV and thalamic volume outcomes in MS patients while on treatment with fingolimod. Iron depletion combined with increased myelin density due to gray matter loss may be the main driver of reduced thalamic susceptibility in MS patients over 12 months.
Disclosure: Study Disclosures:
Study was supported in part by Novartis Pharmaceuticals AG, Switzerland.
Financial Relationships/Potential Conflicts of Interest:
Robert Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Celgene and Novartis for speaking and consultant fees. He received financial support for research activities from Genzyme-Sanofi, Novartis, Claret Medical, Protembo and IMS Health.
Ralph RH. Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec.
Niels Bergsland, Jesper Hagemeier, Dejan Jakimovski, Deepa P. Ramasamy and Ellen Carl have nothing to disclose.
Ferdinand Schweser received personal compensation from Toshiba Canada Medical Systems Limited and Goodwin Procter LLP for speaking and consultant fees. He received financial support for research activities from SynchroPET Inc. and travel sponsorship from GE Healthcare and SynchroPET Inc.
Michael G. Dwyer has received consultant fees from Claret Medical and research grant support from Novartis.
David Hojnacki has received speaker honoraria and consultant fees from Biogen Idec, Teva Pharmaceutical Industries Ltd., EMD Serono, Pfizer Inc, and Novartis.
Channa Kolb has received speaker honoraria and consultant fees from EMD Serono, Teva Pharmaceuticals, Acorda, Novartis, Genzyme and Biogen-Idec.
Dr. Murali Ramanathan received research funding the National Multiple Sclerosis Society, the National Institutes of Health and Otsuka Pharmaceutical and Development. These are unrelated to the research presented in this report.
Bianca Weinstock- Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis, Acorda.
Abstract: P812
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: No longitudinal studies in multiple sclerosis (MS) examined the effect of fingolimod on development of thalamic pathology, progression of cognitive impairment, and their association with evolution of environmental risk factors.
Objectives: To assess the effect of fingolimod on thalamic pathology (as measured by volume and susceptibility changes), cognitive deterioration and humoral response to Epstein-Barr virus (EBV) over 24 months in patients with relapsing MS.
Methods: This was a prospective, observational, single-blinded study of 20 relapsing MS patients starting treatment with fingolimod, and 20 age- and sex-matched healthy controls (HCs). Subjects were assessed at baseline, 6, 12, and 24 months with clinical, cognitive, MRI, and humoral response to EBV examinations. MRI outcomes included thalamic volume and susceptibility measurements from baseline to 24 months. Baseline group effect differences (MS vs. HCs) were investigated using analysis of covariance analysis adjusted for age and sex. The differences over time, between MS and HCs, were investigated by using interaction effect of group by time (RM-ANCOVA).
Results: MS patients remained clinically stable over 24 months. There were no significant differences between MS and HCs in cognitive or EBV changes over 24 months. At baseline, MS patients had lower thalamic volume (p< 0.001) and susceptibility (p=0.003) compared to HCs. Over the follow-up, no significant differences in thalamic volume changes were found between MS patients and HCs. However, there was a significant reduction in thalamic susceptibility between MS and HCs, which was significant at 0-6 months (p=0.002), 6-12 months (p=0.042) and 0-12 months (p=0.042), but not 0-24 months (p=0.185).
Conclusions: This 24-month study showed stability of clinical, cognitive, EBV and thalamic volume outcomes in MS patients while on treatment with fingolimod. Iron depletion combined with increased myelin density due to gray matter loss may be the main driver of reduced thalamic susceptibility in MS patients over 12 months.
Disclosure: Study Disclosures:
Study was supported in part by Novartis Pharmaceuticals AG, Switzerland.
Financial Relationships/Potential Conflicts of Interest:
Robert Zivadinov received personal compensation from EMD Serono, Genzyme-Sanofi, Celgene and Novartis for speaking and consultant fees. He received financial support for research activities from Genzyme-Sanofi, Novartis, Claret Medical, Protembo and IMS Health.
Ralph RH. Benedict has acted as a consultant or scientific advisory board member for Bayer, Biogen Idec, Actelion, and Novartis. He receives royalties from Psychological Assessment Resources, Inc. He has received financial support for research activities from Shire Pharmaceuticals, Accorda and Biogen Idec.
Niels Bergsland, Jesper Hagemeier, Dejan Jakimovski, Deepa P. Ramasamy and Ellen Carl have nothing to disclose.
Ferdinand Schweser received personal compensation from Toshiba Canada Medical Systems Limited and Goodwin Procter LLP for speaking and consultant fees. He received financial support for research activities from SynchroPET Inc. and travel sponsorship from GE Healthcare and SynchroPET Inc.
Michael G. Dwyer has received consultant fees from Claret Medical and research grant support from Novartis.
David Hojnacki has received speaker honoraria and consultant fees from Biogen Idec, Teva Pharmaceutical Industries Ltd., EMD Serono, Pfizer Inc, and Novartis.
Channa Kolb has received speaker honoraria and consultant fees from EMD Serono, Teva Pharmaceuticals, Acorda, Novartis, Genzyme and Biogen-Idec.
Dr. Murali Ramanathan received research funding the National Multiple Sclerosis Society, the National Institutes of Health and Otsuka Pharmaceutical and Development. These are unrelated to the research presented in this report.
Bianca Weinstock- Guttman received honoraria as a speaker and as a consultant for Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis and Acorda. Dr Weinstock-Guttman received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme&Sanofi, Novartis, Acorda.