Contributions
Abstract: P641
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Objective: To investigate whether cerebellar volume is a predictor of short and long-term disability in patients with relapsing-remitting multiple sclerosis (RRMS).
Background: Cerebellum has a predilection for demyelination in MS, and its atrophy strongly contributes to disease-related impairment in MS. Cerebellar volume loss over one-year has been reported as predictor of disease worsening in progressive MS patients. However, the predictive role of baseline cerebellar volume has never been tested in a large group of MS patients over time.
Methods: MRI data from the first 76 of 1,008 RRMS patients who participated in the multi-center, randomized, phase III CombiRx Trial were analyzed. All patients were under immuno-modulatory treatment with either glatiramer acetate (n=19), interferon β-1a (n=19) or glatiramer acetate + interferon β-1a (n=38). On the baseline MRI scans, whole brain T2 and gadolinium (Gd)-enhancing lesion number where obtained using MRIAP, while grey matter fraction (GMF) and cerebellar volume were measured using SPM12. Clinical measures included the Multiple Sclerosis Functional Composite (MSFC), evaluated at baseline and 6, 12, and 24 month follow-up evaluations. A hierarchical multiple linear regression analysis was performed to assess the relationship among baseline T2 hyperintense and Gd-enhancing lesion number, GMF, cerebellar GM volume and clinical disability at baseline and follow-ups, adjusted for age, gender, disease duration and acquisition center.
Results: The regression model including T2 and Gd-enhancing lesion number, GMF and cerebellar GM volume, significantly correlated with the clinical impairment at baseline (R2 = 0.17, p = 0.02), and predicted subsequent impairment 6 (R2 = 0.26, p = 0.001), 12 (R2 = 0.27, p = 0.002) and 24 months
(R2 = 0.24, p = 0.01), with cerebellar volume being an independent predictor of MSFC at all time points (respectively, Beta = 0.32, p = 0.009; Beta = 0.37, p = 0.002; Beta = 0.26, p = 0.03;
Beta = 0.31, p = 0.03).
Conclusions: These preliminary results suggest that cerebellar volume is an independent predictor of short- and longer-term clinical disability in MS patients as measured by MSFC. The study is ongoing and results from the entire trial population will be presented.
Disclosure:
Dr. Petracca reports a research fellowhip from FISM
Dr. Cocozza reports personal fees from Sanofi Genzyme
Dr. Freeman: nothing to disclose
Mr. Kangarlu: nothing to disclose
Dr. Stephen Krieger has served as a consultant for Acorda Therapeutics, Bayer, Biogen, EMD Serono, Genentech, Genzyme Corporation, Novartis, and Teva Pharmaceutical Industries. He has participated in Industry-Sponsored Non-Promotional, Non-Marketing Lectures for Genzyme Corporation, Genentech, and Biogen Idec
served on data and safety monitoring boards for AMO Pharma, Apotek, Biogen Idec, GlaxoSmithKline Pharmaceuticals, Gilead Pharmaceuticals, Horizon Pharmaceuticals, Merck Pharmaceuticals, Modigenetech/Prolor, Opko, Neuren, Sanofi-Aventis, Teva, and NHLBI (protocol review committee); NICHD (OPRU oversight committee), consulting or advisory boards for CereSpir, Inc., Consortium of MS Centers, D3, Genentech, Genzyme, Innate Therapeutics, Janssen Pharmaceuticals, Klein Buendel, Inc., Medday, MedImmune, Novartis, Opexa Therapeutics, Receptos, Roche, Savara Inc., Somahlution, Spinifex Pharmaceuticals, Teva, TG Therapeutics, and Transparency Life Sciences.
Dr. Wolinsky has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, AcademicCME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, Medday Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals, WebMD; royalties are received for out licensed monoclonal antibodies through UTHealth from Millipore Corporation.
Dr. Lublin reports grants and personal fees from Novartis, Biogen Idec, Teva Neuroscience, Sanofi/Genzyme, Celgene, grants from Transparency Life Sciences and personal fees from Bayer Healthcare, EMD Serono, Actelion, Acorda, Questcor/Malinckrodt, Roche/Genentech, Medimmune, Osmotica, Xenoport, Receptos, Forward pharma, BBB Technologies, Akros, TG therapeutics, Abbvie, MedDay and Atara Biotherappeutics.
Dr. Inglese reports grants from Novartis Pharmaceuticals, National Multiple Sclerosis Society, Noto Foundation, NIH and Teva Neuroscience.
Abstract: P641
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 25 Biomarkers
Objective: To investigate whether cerebellar volume is a predictor of short and long-term disability in patients with relapsing-remitting multiple sclerosis (RRMS).
Background: Cerebellum has a predilection for demyelination in MS, and its atrophy strongly contributes to disease-related impairment in MS. Cerebellar volume loss over one-year has been reported as predictor of disease worsening in progressive MS patients. However, the predictive role of baseline cerebellar volume has never been tested in a large group of MS patients over time.
Methods: MRI data from the first 76 of 1,008 RRMS patients who participated in the multi-center, randomized, phase III CombiRx Trial were analyzed. All patients were under immuno-modulatory treatment with either glatiramer acetate (n=19), interferon β-1a (n=19) or glatiramer acetate + interferon β-1a (n=38). On the baseline MRI scans, whole brain T2 and gadolinium (Gd)-enhancing lesion number where obtained using MRIAP, while grey matter fraction (GMF) and cerebellar volume were measured using SPM12. Clinical measures included the Multiple Sclerosis Functional Composite (MSFC), evaluated at baseline and 6, 12, and 24 month follow-up evaluations. A hierarchical multiple linear regression analysis was performed to assess the relationship among baseline T2 hyperintense and Gd-enhancing lesion number, GMF, cerebellar GM volume and clinical disability at baseline and follow-ups, adjusted for age, gender, disease duration and acquisition center.
Results: The regression model including T2 and Gd-enhancing lesion number, GMF and cerebellar GM volume, significantly correlated with the clinical impairment at baseline (R2 = 0.17, p = 0.02), and predicted subsequent impairment 6 (R2 = 0.26, p = 0.001), 12 (R2 = 0.27, p = 0.002) and 24 months
(R2 = 0.24, p = 0.01), with cerebellar volume being an independent predictor of MSFC at all time points (respectively, Beta = 0.32, p = 0.009; Beta = 0.37, p = 0.002; Beta = 0.26, p = 0.03;
Beta = 0.31, p = 0.03).
Conclusions: These preliminary results suggest that cerebellar volume is an independent predictor of short- and longer-term clinical disability in MS patients as measured by MSFC. The study is ongoing and results from the entire trial population will be presented.
Disclosure:
Dr. Petracca reports a research fellowhip from FISM
Dr. Cocozza reports personal fees from Sanofi Genzyme
Dr. Freeman: nothing to disclose
Mr. Kangarlu: nothing to disclose
Dr. Stephen Krieger has served as a consultant for Acorda Therapeutics, Bayer, Biogen, EMD Serono, Genentech, Genzyme Corporation, Novartis, and Teva Pharmaceutical Industries. He has participated in Industry-Sponsored Non-Promotional, Non-Marketing Lectures for Genzyme Corporation, Genentech, and Biogen Idec
served on data and safety monitoring boards for AMO Pharma, Apotek, Biogen Idec, GlaxoSmithKline Pharmaceuticals, Gilead Pharmaceuticals, Horizon Pharmaceuticals, Merck Pharmaceuticals, Modigenetech/Prolor, Opko, Neuren, Sanofi-Aventis, Teva, and NHLBI (protocol review committee); NICHD (OPRU oversight committee), consulting or advisory boards for CereSpir, Inc., Consortium of MS Centers, D3, Genentech, Genzyme, Innate Therapeutics, Janssen Pharmaceuticals, Klein Buendel, Inc., Medday, MedImmune, Novartis, Opexa Therapeutics, Receptos, Roche, Savara Inc., Somahlution, Spinifex Pharmaceuticals, Teva, TG Therapeutics, and Transparency Life Sciences.
Dr. Wolinsky has served on advisory boards, data monitoring or steering committees, has consulting agreements, or received speaker honoraria from the following entities: AbbVie, AcademicCME, ACTRIMS, Alkermes, Bayer HealthCare, Biogen, Bionest, Celgene, Clene Nanomedicine, CMSC, ECTRIMS, Forward Pharma A/S, Medday Pharmaceuticals, Novartis Pharmaceuticals, PRIME, Roche Genentech, Sanofi Genzyme, Strategic Consultants International, Takeda, Teva Pharmaceuticals, WebMD; royalties are received for out licensed monoclonal antibodies through UTHealth from Millipore Corporation.
Dr. Lublin reports grants and personal fees from Novartis, Biogen Idec, Teva Neuroscience, Sanofi/Genzyme, Celgene, grants from Transparency Life Sciences and personal fees from Bayer Healthcare, EMD Serono, Actelion, Acorda, Questcor/Malinckrodt, Roche/Genentech, Medimmune, Osmotica, Xenoport, Receptos, Forward pharma, BBB Technologies, Akros, TG therapeutics, Abbvie, MedDay and Atara Biotherappeutics.
Dr. Inglese reports grants from Novartis Pharmaceuticals, National Multiple Sclerosis Society, Noto Foundation, NIH and Teva Neuroscience.