Contributions
Abstract: P1115
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Objective: To monitor changes in myelin over 48 months in relapsing multiple sclerosis (RMS) patients treated with ocrelizumab.
Background: Ocrelizumab (OCR) is an approved disease modifying therapy for RMS. Myelin water imaging (MWI) quantifies the amount of signal from water trapped within myelin bilayers as the myelin water fraction (MWF). We used MWI to measure myelin content over 48 months in white matter regions in RMS patients treated with either continuous OCR or with interferon beta-1a (IFN) during the first 24 months followed by OCR for 24 months.
Methods: Fifty-six RMS subjects participating in a substudy of OPERA II (NCT01412333) had MWI acquired over 48 months on a 3T MR scanner. Thirty subjects received OCR every 6 months for 48 months, starting at baseline. Twenty-six subjects were treated with IFN for 24 months starting at baseline and then switched to OCR every 6 months for the next 24 months. The MWF mean was measured across whole brain normal appearing white matter (NAWM) and in specific regions of interest known to be affected by MS: corpus callosum (CC) and cortical spinal tract (CST). A mixed effects model with repeated measures was used to compare between timepoints and between subgroups.
Results: In whole brain NAWM, we found a decrease in the MWF in subjects treated with IFN from month 0 (0.204±0.019) to 6 (0.199±0.016), p=0.035. In the CC, the IFN subgroup showed decreasing MWF during the first 24 months (m0: 0.191±0.019, m24: 0.183±0.017), followed by increasing MWF during the next 24 months after switching to OCR (m48: 0.189±0.020). The OCR subgroup showed unchanging MWF over 48 months (m0: 0.192±0.016, m24: 0.191±0.016, m48: 0.195±0.016). In the CST, the IFN subgroup showed a decrease between month 0 (0.201±0.019) and 48 (0.195±0.016), and stability after switching to OCR. The OCR subgroup had no change in MWF over 48 months. In both regions, at early timepoints the percent change in MWF was significantly different between IFN (-4.03±0.86) and OCR (-0.45±0.76, p=0.007) but the difference disappeared at later timepoints when both groups were treated with OCR.
Conclusion: Stability or increases in MWF were detected in both subjects who started OCR treatment from the beginning of the study as well as those that switched to OCR treatment after 24 months. The use of advanced imaging metrics (such as myelin water imaging) in clinical trials may provide specific information about tissue damage.
Disclosure: Funded by F. Hoffmann-LaRoche. IM Vavasour, C Taylor, R Tam: nothing to disclose. DKB Li: Research funding from the Canadian Institute of Health Research and MS Society of Canada. 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. 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. Given lectures which have been supported by non-restricted education grants from Academy of Health Care Learning, Biogen-Idec, Consortium of MS Centers, Novartis, Sanofi-Genzyme and Teva. V. Levesque, H. Garren, D. Clayton: employees of Genentech. A. Traboulsee: Research funding from Chugai, Roche, Novartis, Genzyme, Biogen. Consultancy honoraria from Genzyme, Roche, Teva, Biogen, Serono S.H. Kolind: Research funding from F. Hoffmann La Roche, Sanofi Genzyme MS society of Canada and NSERC.
Abstract: P1115
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Objective: To monitor changes in myelin over 48 months in relapsing multiple sclerosis (RMS) patients treated with ocrelizumab.
Background: Ocrelizumab (OCR) is an approved disease modifying therapy for RMS. Myelin water imaging (MWI) quantifies the amount of signal from water trapped within myelin bilayers as the myelin water fraction (MWF). We used MWI to measure myelin content over 48 months in white matter regions in RMS patients treated with either continuous OCR or with interferon beta-1a (IFN) during the first 24 months followed by OCR for 24 months.
Methods: Fifty-six RMS subjects participating in a substudy of OPERA II (NCT01412333) had MWI acquired over 48 months on a 3T MR scanner. Thirty subjects received OCR every 6 months for 48 months, starting at baseline. Twenty-six subjects were treated with IFN for 24 months starting at baseline and then switched to OCR every 6 months for the next 24 months. The MWF mean was measured across whole brain normal appearing white matter (NAWM) and in specific regions of interest known to be affected by MS: corpus callosum (CC) and cortical spinal tract (CST). A mixed effects model with repeated measures was used to compare between timepoints and between subgroups.
Results: In whole brain NAWM, we found a decrease in the MWF in subjects treated with IFN from month 0 (0.204±0.019) to 6 (0.199±0.016), p=0.035. In the CC, the IFN subgroup showed decreasing MWF during the first 24 months (m0: 0.191±0.019, m24: 0.183±0.017), followed by increasing MWF during the next 24 months after switching to OCR (m48: 0.189±0.020). The OCR subgroup showed unchanging MWF over 48 months (m0: 0.192±0.016, m24: 0.191±0.016, m48: 0.195±0.016). In the CST, the IFN subgroup showed a decrease between month 0 (0.201±0.019) and 48 (0.195±0.016), and stability after switching to OCR. The OCR subgroup had no change in MWF over 48 months. In both regions, at early timepoints the percent change in MWF was significantly different between IFN (-4.03±0.86) and OCR (-0.45±0.76, p=0.007) but the difference disappeared at later timepoints when both groups were treated with OCR.
Conclusion: Stability or increases in MWF were detected in both subjects who started OCR treatment from the beginning of the study as well as those that switched to OCR treatment after 24 months. The use of advanced imaging metrics (such as myelin water imaging) in clinical trials may provide specific information about tissue damage.
Disclosure: Funded by F. Hoffmann-LaRoche. IM Vavasour, C Taylor, R Tam: nothing to disclose. DKB Li: Research funding from the Canadian Institute of Health Research and MS Society of Canada. 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. 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. Given lectures which have been supported by non-restricted education grants from Academy of Health Care Learning, Biogen-Idec, Consortium of MS Centers, Novartis, Sanofi-Genzyme and Teva. V. Levesque, H. Garren, D. Clayton: employees of Genentech. A. Traboulsee: Research funding from Chugai, Roche, Novartis, Genzyme, Biogen. Consultancy honoraria from Genzyme, Roche, Teva, Biogen, Serono S.H. Kolind: Research funding from F. Hoffmann La Roche, Sanofi Genzyme MS society of Canada and NSERC.