Contributions
Abstract: P540
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Objective: To use MRI to monitor changes in myelin water fraction over 5 years in multiple sclerosis (MS) patients receiving 2 annual courses of treatment of 12 mg/day alemtuzumab.
Background: Alemtuzumab is an effective disease modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). Myelin water imaging (MWI) quantifies the amount of signal from water trapped within myelin bilayers as the myelin water fraction (MWF) and is histopathologically related to myelin content. To test the potential neuroprotective and reparative properties of therapy, we used MWI to measure demyelination and remyelination in vivo in patients treated with either alemtuzumab, SC interferon beta-1a, or no DMT treatment.
Methods: Thirty-eight subjects had MWI at baseline and longitudinally up to 5 years on a 3T Philips MR scanner. Twenty-five subjects received alemtuzumab at baseline and 12 months. Thirteen subjects received a third cycle and one subject received a fourth cycle of alemtuzumab. Five subjects were treated with SC interferon beta-1a 3 times per week. Eight subjects were not treated. Four healthy volunteers were also scanned. The mean MWF was measured across all normal appearing white matter (NAWM) and in stable lesions at all time points up to year 5.
Results: MWF in NAWM showed an average 4% increase in subjects treated with alemtuzumab (baseline=0.094; year 4=0.098; p=0.004) whereas the MWF decreased by ~10% in subjects treated with SC interferon beta-1a (baseline=0.096; year 5=0.088; p=0.01) or without treatment (baseline=0.087; year 5=0.069; p=0.15) over the 5 years. Healthy volunteers MWF did not change over time (baseline=0.102; year 5=0.105). MWF in stable lesions showed no change in any MS cohort over 5 years.
Discussion: The MWF increase following treatment with alemtuzumab alemtuzumab suggests modulation of the immune system can result in myelin recovery. This supports previous clinical trial findings of sustained improvement in EDSS scores in many alemtuzumab patients as well as markedly reduced rates of brain atrophy and provides further understanding of the biological mechanisms underlying observed clinical improvement. The sensitive, specific and quantitative nature of myelin water imaging allowed detection of a treatment effect in a small group, outside of areas of acute damage demonstrating that MWF is a powerful biomarker for neuroprotection in MS.
Disclosure: This study was funded by Sanofi Genzyme.
I Vavasour, C Laule, R Tam and A MacKay have nothing to disclose.
S Kolind received research support from Roche and the MS Society of Canada, and did consulting for Acorda and Genzyme.
D Li received research funding from the Canadian Institute of Health Research and Multiple Sclerosis Society of Canada; is 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 and also received grant support for investigator-initiated independent studies from Genzyme, Merck-Serono, Novartis and Roche; consultant to Vertex Pharmaceuticals; served on the Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Celgene, Novartis and Roche; given lectures supported by non-restricted education grants from Teva, Novartis and Biogen.
R Carruthers is a site principal investigator for studies funded by MedImmune, Teva, and Guthy Jackson. He has received speaking fees for unbranded lectures from Biogen, Genzyme, and Teva. He has received consulting fees for Novartis, EMD Serono, and Genzyme.
A Traboulsee did consulting for Biogen, Roche, EMD Serono and Teva Pharmaceuticals,and received research support from Biogen, Chugai, CIHR, Roche, Michael Smith Foundation and the MS Society of Canada.
Abstract: P540
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Objective: To use MRI to monitor changes in myelin water fraction over 5 years in multiple sclerosis (MS) patients receiving 2 annual courses of treatment of 12 mg/day alemtuzumab.
Background: Alemtuzumab is an effective disease modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS). Myelin water imaging (MWI) quantifies the amount of signal from water trapped within myelin bilayers as the myelin water fraction (MWF) and is histopathologically related to myelin content. To test the potential neuroprotective and reparative properties of therapy, we used MWI to measure demyelination and remyelination in vivo in patients treated with either alemtuzumab, SC interferon beta-1a, or no DMT treatment.
Methods: Thirty-eight subjects had MWI at baseline and longitudinally up to 5 years on a 3T Philips MR scanner. Twenty-five subjects received alemtuzumab at baseline and 12 months. Thirteen subjects received a third cycle and one subject received a fourth cycle of alemtuzumab. Five subjects were treated with SC interferon beta-1a 3 times per week. Eight subjects were not treated. Four healthy volunteers were also scanned. The mean MWF was measured across all normal appearing white matter (NAWM) and in stable lesions at all time points up to year 5.
Results: MWF in NAWM showed an average 4% increase in subjects treated with alemtuzumab (baseline=0.094; year 4=0.098; p=0.004) whereas the MWF decreased by ~10% in subjects treated with SC interferon beta-1a (baseline=0.096; year 5=0.088; p=0.01) or without treatment (baseline=0.087; year 5=0.069; p=0.15) over the 5 years. Healthy volunteers MWF did not change over time (baseline=0.102; year 5=0.105). MWF in stable lesions showed no change in any MS cohort over 5 years.
Discussion: The MWF increase following treatment with alemtuzumab alemtuzumab suggests modulation of the immune system can result in myelin recovery. This supports previous clinical trial findings of sustained improvement in EDSS scores in many alemtuzumab patients as well as markedly reduced rates of brain atrophy and provides further understanding of the biological mechanisms underlying observed clinical improvement. The sensitive, specific and quantitative nature of myelin water imaging allowed detection of a treatment effect in a small group, outside of areas of acute damage demonstrating that MWF is a powerful biomarker for neuroprotection in MS.
Disclosure: This study was funded by Sanofi Genzyme.
I Vavasour, C Laule, R Tam and A MacKay have nothing to disclose.
S Kolind received research support from Roche and the MS Society of Canada, and did consulting for Acorda and Genzyme.
D Li received research funding from the Canadian Institute of Health Research and Multiple Sclerosis Society of Canada; is 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 and also received grant support for investigator-initiated independent studies from Genzyme, Merck-Serono, Novartis and Roche; consultant to Vertex Pharmaceuticals; served on the Data and Safety Advisory Board for Opexa Therapeutics and Scientific Advisory Boards for Adelphi Group, Celgene, Novartis and Roche; given lectures supported by non-restricted education grants from Teva, Novartis and Biogen.
R Carruthers is a site principal investigator for studies funded by MedImmune, Teva, and Guthy Jackson. He has received speaking fees for unbranded lectures from Biogen, Genzyme, and Teva. He has received consulting fees for Novartis, EMD Serono, and Genzyme.
A Traboulsee did consulting for Biogen, Roche, EMD Serono and Teva Pharmaceuticals,and received research support from Biogen, Chugai, CIHR, Roche, Michael Smith Foundation and the MS Society of Canada.