Contributions
Abstract: P479
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Gadolinium-based contrast agents (GBCA) commonly used in routine neuroimaging can accumulate in the brain's deep gray matter structures despite chelation. A clinical trial of secondary progressive multiple sclerosis (SPMS) patients included an infrequent (IFR) and a frequent (FR) MRI cohort who received 1-4 or 5-11 GBCA injections over 104 weeks. By evaluating the clinical outcomes of these two cohorts, this retrospective study was performed to assess the potential dose-dependent effect of GBCA on MS progression.
Objective: To evaluate the potential dose-dependent effect of GBCA on MS progression
Materials and methods: Clinical outcomes from a cohort of 612 SPMS patients, enrolled in a 2-year placebo-controlled (negative) trial assessing the efficacy of MBP8298, were acquired. Patients received 1-4 (infrequent cohort; IFR) or 5-11 (frequent cohort; FR) GBCA injections between screening (week -4) and week 104. The primary clinical outcome was the change in Expanded Disability Status Scale (EDSS) and time to confirmed EDSS progression and secondary outcomes included the changes of Multiple Sclerosis Functional Composite (MSFC), Timed 25-Foot Walk (T25FW), the 9-Hole-Peg Test (9HPT), the Paced Auditory Serial Addition Test (PASAT) from baseline to week 104.
Results: The 512 IFR and 100 FR participants showed no differences in baseline demographics or disease history. The mean change from baseline to week 104 in EDSS was +0.21(IFR) and +0.13(FR); MSFC -0.38(IFR) and -0.14(FR); T25FW +1.28(IFR) and +0.55(FR); 9HPT -0.06(IFR) and -0.08(FR); PASAT +0.22(IFR) and +0.20(FR). The FR to IFR progression hazard ratio was at 0.68 (p=0.09) favouring the FR cohort. There were no significant differences in any of the outcomes between the FR and the IFR cohorts.
Conclusion: There were no differences in the clinical outcome measures of disability progression between the two groups for different GBCA exposure indicating that gadolinium does not result in greater clinical worsening in SPMS in the short term, after two years of follow up.
Disclosure: Nathalie Ackermans has received a grant funding from Sanofi-Genzyme and Biogen for her one-year research fellowship in MS. Anthony Traboulsee has received grant funding from the MS Society of Canada, Canadian Institute for Health Research, Roche, and Genzyme; received honoraria or travel grants from Teva Canada Innovation, Roche, Genzyme, Chugai Pharmaceuticals. Mark S. Freedman has received a research / educational grant from Genzyme; received honoraria or consultation fees from Actelion, BayerHealthcare, BiogenIdec, Chugai, Clene Nanomedicine, EMD Canada, Genzyme, Merck Serono, Novartis, Hoffman La-Roche, Sanofi-Aventis, Teva Canada Innovation; is member of a company advisory board, board of directors or other similar group of Actelion, BayerHealthcare, BiogenIdec, Hoffman La-Roche, Merck Serono, MedDay, Novartis, Sanofi-Aventis and is on speaker's bureau for Genzyme. David Li has received research funding from the Canadian Institute of Health Research and Multiple Sclerosis Society of Canada. He is the Emeritus Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Novartis, Perceptives, Roche and Sanofi-Aventis. The UBC MS/MRI Research Group has also received grant support for investigator-initiated independent studies from Genzyme, Merck-Serono, Novartis and Roche. He has acted as a consultant to Vertex Pharmaceuticals and served on the Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Celgene, Novartis and Roche. He has also given lectures which have been supported by non-restricted education grants from Biogen-Idec, Novartis, Sanofi-Genzyme and Teva. Roger Tam has received research support as part of sponsored clinical studies from Novartis, Roche, and Sanofi Genzyme. Shannon Kolind has received a research / educational grant funding from Genzyme; received honoraria or consultation fees from Acorda and Genzyme; she is member of a company advisory board, board of directors or other similar group of Acorda and Genzyme. Dr. Robert Carruthers has received grants/research from MedImmune, Teva and Guthy Jackson; received speaking fees for unbranded lectures from Biogen, Genzyme and Teva and received consulting fees from Novartis, EMD Serono and Genzyme. Carolyn Taylor and Heejun Kang have nothing to disclose.
Funding: No targeted funding reported.
Abstract: P479
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Gadolinium-based contrast agents (GBCA) commonly used in routine neuroimaging can accumulate in the brain's deep gray matter structures despite chelation. A clinical trial of secondary progressive multiple sclerosis (SPMS) patients included an infrequent (IFR) and a frequent (FR) MRI cohort who received 1-4 or 5-11 GBCA injections over 104 weeks. By evaluating the clinical outcomes of these two cohorts, this retrospective study was performed to assess the potential dose-dependent effect of GBCA on MS progression.
Objective: To evaluate the potential dose-dependent effect of GBCA on MS progression
Materials and methods: Clinical outcomes from a cohort of 612 SPMS patients, enrolled in a 2-year placebo-controlled (negative) trial assessing the efficacy of MBP8298, were acquired. Patients received 1-4 (infrequent cohort; IFR) or 5-11 (frequent cohort; FR) GBCA injections between screening (week -4) and week 104. The primary clinical outcome was the change in Expanded Disability Status Scale (EDSS) and time to confirmed EDSS progression and secondary outcomes included the changes of Multiple Sclerosis Functional Composite (MSFC), Timed 25-Foot Walk (T25FW), the 9-Hole-Peg Test (9HPT), the Paced Auditory Serial Addition Test (PASAT) from baseline to week 104.
Results: The 512 IFR and 100 FR participants showed no differences in baseline demographics or disease history. The mean change from baseline to week 104 in EDSS was +0.21(IFR) and +0.13(FR); MSFC -0.38(IFR) and -0.14(FR); T25FW +1.28(IFR) and +0.55(FR); 9HPT -0.06(IFR) and -0.08(FR); PASAT +0.22(IFR) and +0.20(FR). The FR to IFR progression hazard ratio was at 0.68 (p=0.09) favouring the FR cohort. There were no significant differences in any of the outcomes between the FR and the IFR cohorts.
Conclusion: There were no differences in the clinical outcome measures of disability progression between the two groups for different GBCA exposure indicating that gadolinium does not result in greater clinical worsening in SPMS in the short term, after two years of follow up.
Disclosure: Nathalie Ackermans has received a grant funding from Sanofi-Genzyme and Biogen for her one-year research fellowship in MS. Anthony Traboulsee has received grant funding from the MS Society of Canada, Canadian Institute for Health Research, Roche, and Genzyme; received honoraria or travel grants from Teva Canada Innovation, Roche, Genzyme, Chugai Pharmaceuticals. Mark S. Freedman has received a research / educational grant from Genzyme; received honoraria or consultation fees from Actelion, BayerHealthcare, BiogenIdec, Chugai, Clene Nanomedicine, EMD Canada, Genzyme, Merck Serono, Novartis, Hoffman La-Roche, Sanofi-Aventis, Teva Canada Innovation; is member of a company advisory board, board of directors or other similar group of Actelion, BayerHealthcare, BiogenIdec, Hoffman La-Roche, Merck Serono, MedDay, Novartis, Sanofi-Aventis and is on speaker's bureau for Genzyme. David Li has received research funding from the Canadian Institute of Health Research and Multiple Sclerosis Society of Canada. He is the Emeritus Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Novartis, Perceptives, Roche and Sanofi-Aventis. The UBC MS/MRI Research Group has also received grant support for investigator-initiated independent studies from Genzyme, Merck-Serono, Novartis and Roche. He has acted as a consultant to Vertex Pharmaceuticals and served on the Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Celgene, Novartis and Roche. He has also given lectures which have been supported by non-restricted education grants from Biogen-Idec, Novartis, Sanofi-Genzyme and Teva. Roger Tam has received research support as part of sponsored clinical studies from Novartis, Roche, and Sanofi Genzyme. Shannon Kolind has received a research / educational grant funding from Genzyme; received honoraria or consultation fees from Acorda and Genzyme; she is member of a company advisory board, board of directors or other similar group of Acorda and Genzyme. Dr. Robert Carruthers has received grants/research from MedImmune, Teva and Guthy Jackson; received speaking fees for unbranded lectures from Biogen, Genzyme and Teva and received consulting fees from Novartis, EMD Serono and Genzyme. Carolyn Taylor and Heejun Kang have nothing to disclose.
Funding: No targeted funding reported.