Siponimod Reduces Grey Matter Atrophy in Patients with Secondary Progressive Multiple Sclerosis: Subgroup Analyses from the EXPAND Study (1130)

Objective: To investigate the effect of siponimod versus placebo in reducing cortical grey matter (cGM) and thalamic atrophy in subgroups of secondary progressive multiple sclerosis (SPMS) patients in the EXPAND study. Background: Grey matter (GM) atrophy is more pronounced in progressive forms of multiple sclerosis and is associated with long-term irreversible disability accumulation. Siponimod significantly reduced GM atrophy in patients with SPMS, as reported previously. Design/Methods: This post-hoc analysis included the per-protocol EXPAND study data set (N=1560, patients with major protocol deviations and data after treatment switch excluded). Percent volume change in cGM and thalamus relative to baseline at Month (M)12 and M24 was assessed, and the effect of siponimod versus placebo determined using a mixed-model for repeated measures in SPMS patient subgroups defined by baseline ‘age’ (≤45/>45 years), ‘disease duration’ (≤15/>15 years), ‘Expanded Disability Status Scale score’ ( 43), and ‘pretreatment disease activity’ (active/non-active). Results: Over the course of treatment, in the placebo group, percent volume change from baseline to M24 of cGM was similar across all subgroups (−1.17 to −0.94); whereas for thalamus it differed (−3.56 to −1.31) and was more pronounced in subgroups ‘with gadolinium-lesion activity’ (−3.56), ‘active disease’ (−2.15), ‘age ≤45 years’ (−2.12), ‘disease duration ≤15 years’ (−2.09), and ‘SDMT score ≤43’ (−1.99). Across the subgroups studied, siponimod reduced cGM atrophy versus placebo by 48% to 116% (p 15 years’ p=0.1029 at M12). Conclusions: Siponimod consistently reduced cGM and thalamic atrophy across SPMS subgroups, including those with less active and more advanced disease. Combined with other analyses, these effects might potentially translate into a favorable impact on long-term clinical outcome including disability progression and cognitive decline. Disclosure: Dr. Fox has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Robert Fox has received compensation for serving as a consultant or speaker from Actelion, Biogen, Celgene, EMD Serono, Genentech, Immunic, Novartis, and Teva. He, or the institution he works for, has received research support from Novartis.. Dr. Fox has received research support from He, or the institution he works for, has received research support from Novartis..Dr. Arnold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Consultant fees from Albert Charitable Trust, Biogen, Celgene, F. Hoffmann-La Roche, Frequency Therapeutics, MedDay, Merck Serono, Novartis, Sanofi-Aventis. Dr. Arnold holds stock and/or stock options in NeuroRx Research. Dr. Arnold has received research support from Research grants from Albert Charitable Trust, Biogen, Celgene, F. Hoffmann-La Roche, Frequency Therapeutics, MedDay, Merck Serono, Novartis, Sanofi-Aventis. Dr. Giovannoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Actelion, Atara Biotherapeutics, Bayer, Biogen, Canbex Therapeutics, Five Prime Therapeutics, GSK, GW Pharmaceuticals, Merck, Merck Serono, Novartis, Oxford PharmaGenesis, Protein Discovery Laboratories, Roche, Sanofi Genzyme, Synthon, Teva, and UCB. Dr. Giovannoni has receive research support from AbbVie, Actelion, Atara Biotherapeutics, Bayer, Biogen, Canbex Therapeutics, Five Prime Therapeutics, GSK, GW Pharmaceuticals, Merck, Merck Serono, Novartis, Oxford PharmaGenesis, Protein Discovery Laboratories, Roche, Sanofi Genzyme, Synthon, Teva, and UCB.Dr. Cree has received personal compensation from Akili, Alexion, Atara, Biogen, EMD Serono, Novartis, TG Therapeutics.Dr. Vermersch has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva. Dr. Vermersch has received research support from Almirall, Biogen, Celgene, Merck Serono, Novartis, Roche, Sanofi, Servier, and Teva.Amit Bar-Or has participated as a speaker in meetings sponsored by, and received consulting fees from, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, Janssen/Actelion, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme. Grant support from Janssen/Actelion, Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Roche/Genentech, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi-Genzyme.Dr. Gold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Diseases, Experimental Neurology and the Journal of Neuroimmunology. Dr. Gold has received research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis.Dr. Benedict has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ralph H. B. Benedict is on the speakers’ bureau for EMD Serono, and consults for Biogen Idec, Genentech, Roche, Sanofi/Genzyme, Takeda, NeuroCog Trials, and Novartis.. Dr. Benedict has received royalty, license fees, or contractual rights payments from Psychological Assessment Resources. Dr. Benedict has received research support from Ralph H. B. Benedict has received research support from Accorda, Novartis, Genzyme, Biogen Idec, and Mallinkrodt, and is on the speakers’ bureau for EMD Serono.. Dr. Piani Meier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharma AG, Basel, Switzerland. Dr. Arnould has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Novartis. Dr. Ritter has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharmaceuticals Corporation, NJ, USA. Dr. Dahlke has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharma AG, Basel, Switzerland. Dr. Karlsson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Novartis Pharma AG, Basel, Switzerland. Dr. Kappos has received research support from Bayer, Biogen, Innosuisse, Novartis, the Swiss MS Society, the Swiss National Research Foundation, and the European Union.