RT Journal Article
SR Electronic
T1 Long-term Effect of Siponimod on MRI Outcomes in SPMS: Analyses from the EXPAND Study up to 5 Years (2217)
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 2217
VO 96
IS 15 Supplement
A1 Arnold, Douglas L.
A1 Kappos, Ludwig
A1 Vermersch, Patrick
A1 Gold, Ralf
A1 Bar-Or, Amit
A1 Giovannoni, Gavin
A1 Cree, Bruce A.C.
A1 Meier, Daniela Piani
A1 Ritter, Shannon
A1 Karlsson, Goeril
A1 Dahlke, Frank
A1 Hach, Thomas
A1 Fox, Robert J.
YR 2021
UL http://n.neurology.org/content/96/15_Supplement/2217.abstract
AB Objective: To evaluate the long-term effect of siponimod on volume loss (VL) of whole brain, cortical grey matter (cGM) and thalamus, and changes in T2 lesion volume (T2LV) and cumulative number of new/enlarging T2 (neT2) lesions in the Phase 3 EXPAND extension study.Background: In the EXPAND core study, siponimod compared with placebo significantly reduced disability progression, cognitive decline, MRI measures of focal inflammation, and global and regional brain VL, in SPMS patients.Design/Methods: Of 1651 patients randomized and completing EXPAND core (median 21 months [M]), 1224 entered the 7-year, open-label extension study. Changes in MRI outcomes from EXPAND core baseline to M60 were compared between continuous (siponimod in core/extension) and switch (placebo in core/siponimod in extension) groups. Furthermore, within group comparisons for annualized rate of brain atrophy [ARBA]), and yearly T2LV change and neT2 counts in extension versus core were assessed. Data were analyzed using non-parametric methods and models for repeated measures.Results: At M60, treatment effects on VL of whole brain (−1.62% vs −1.76%, p<0.05) and thalamus (−2.68% vs −3.48%, p<0.0001) were more pronounced in the continuous versus switch group; cGM VL was low in both groups (−1.42% vs −1.43%). T2LV change and neT2 counts were reduced in the continuous versus switch group (326 vs 870 mm3 and 3.4 vs 9.3, both p<0.0001). Within-group comparison of extension versus core phase: the switch group recapitulated the pronounced reductions in VL of whole brain (58.1%), cGM (85.4%), and thalamus (58.3%), and yearly T2LV change (94.3%) and neT2 counts (72.8%) on starting siponimod (all, p<0.0001); low ARBA/lesion activity was maintained in the continuous siponimod group.Conclusions: Siponimod treatment showed sustained efficacy on MRI measures, including GM atrophy over the long-term, and benefit upon switching from placebo. Persistent differences between continuous and switch groups in measures of brain tissue integrity highlight the importance of early treatment initiation.Disclosure: Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GENeuro. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Receptos/Celgene. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received stock or an ownership interest from NeuroRx. The institution of Dr. Arnold has received research support from Novartis. The institution of Dr. Arnold has received research support from Immunotec. The institution of Dr. Kappos has received research support from Bayer. The institution of Dr. Kappos has received research support from Biogen. The institution of Dr. Kappos has received research support from Celgene. The institution of Dr. Kappos has received research support from Genentech. The institution of Dr. Kappos has received research support from Gemzyme. The institution of Dr. Kappos has received research support from Janssen. The institution of Dr. Kappos has received research support from Merck Serono. The institution of Dr. Kappos has received research support from Minoryx. The institution of Dr. Kappos has received research support from Novartis. The institution of Dr. Kappos has received research support from Roche. The institution of Dr. Kappos has received research support from Sanofi. The institution of Dr. Kappos has received research support from Santhera. The institution of Dr. Kappos has received research support from TG Therapeutics. The institution of Dr. Kappos has received research support from Abbvie. The institution of Dr. Kappos has received research support from Eisai. The institution of Dr. Kappos has received research support from Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundation, Innosuisse. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Patrick Vermersch has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for La revue des microbiotes. The institution of Patrick Vermersch has received research support from Roche. The institution of Patrick Vermersch has received research support from Sanofi. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen . Dr. Gold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer Vital. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Pharamaceuticals. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gold has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishers. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Novartis. Dr. Gold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Biogen. The institution of Dr. Gold has received research support from Novartis. The institution of Dr. Gold has received research support from Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen/Actelion. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara Biotherapeutics. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merk/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Atara Biotherapeutics. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck/EMD Serono. Dr. Bar-Or has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. The institution of Dr. Bar-Or has received research support from Novartis. The institution of Dr. Bar-Or has received research support from Biogen. The institution of Dr. Bar-Or has received research support from Roche/Genentech. The institution of Dr. Bar-Or has received research support from Merck/EMD Serono. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atara Bio. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Actelion. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Oxford Health Policy Forum. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Neurology Academy. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Peervoice. Dr. Giovannoni has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Bristows . The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Atara. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Akili. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. The institution of Dr. Cree has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Cree has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. The institution of Dr. Cree has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for TG Therapeutics. Dr. Cree has received publishing royalties from a publication relating to health care. Daniela Piani Meier has nothing to disclose. Shannon Ritter has received personal compensation for serving as an employee of Novartis. Dr. Karlsson has received personal compensation for serving as an employee of Novartis Pharma AG. Dr. Dahlke has received personal compensation for serving as an employee of Novartis. Thomas Hach has received personal compensation for serving as an employee of Novartis Pharma AG. Thomas Hach has received stock or an ownership interest from Novartis. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AB Science. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Celgene. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Immunic. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. The institution of Dr. Fox has received research support from National Institutes of Health. Dr. Fox has received publishing royalties from a publication relating to health care.