Siponimod delays the time to wheelchair in patients with SPMS: results from the EXPAND study
ECTRIMS Online Library. Vermersch P. Sep 12, 2019; 279456; 158
Patrick Vermersch
Patrick Vermersch

Abstract: 158

Type: Scientific Session

Abstract Category: Therapy - Others

P. Vermersch1, R. Gold2, L. Kappos3, R. Fox4, A. Bar-Or5, B. Cree6, N. Rouyrre7, S. Arnould7, F. Dahlke7, G. Karlsson7, G. Giovannoni8

1University Lille, INSERM U995, CHU Lille, Lille, France, 2Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum, Bochum, Germany, 3Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland, 4Mellen Centre for Treatment and Research in Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Cleveland, OH, 5Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 6UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, United States, 7Novartis Pharma AG, Basel, Switzerland, 8Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom

Background: Secondary progressive MS (SPMS) is associated with insidious worsening of walking disability, which eventually results in increased dependence on a wheelchair. Siponimod was recently shown to be efficacious in slowing down disability progression and cognitive decline in a typical SPMS population (EXPAND study). Here, we report the effect of siponimod in delaying time to wheelchair dependence.
Objective: To evaluate the effect of siponimod compared to placebo in delaying disability progression to Expanded Disability Status Scale (EDSS) ≥7 (i.e. needing a wheelchair), sustained until the end of the EXPAND study, in patients with SPMS.
Methods: In the EXPAND study, time to reach EDSS ≥7 was assessed post hoc using two different models: a survival analysis and a multistate model. The survival analysis was performed on the subset of patients with a baseline EDSS score of 6.5 who were at high risk of reaching wheelchair during EXPAND study (siponimod, N=293; placebo, N=119). The multistate model was performed on the overall EXPAND population (siponimod, N=1099; placebo, N=546); three disease states were defined based on EDSS values of ≤5, 5.5-6, and 6.5. The transitions from one state to the next and the sojourn times in each state were calculated. The model also predicted time to EDSS ≥7 from any disease state by using all transitions through all intermediate states. Assuming that treatment effect is preserved, results were extrapolated from estimated parameters to calculate median time to progression to EDSS ≥7 for the overall population.
Results: In the survival analysis, compared to placebo, a lower proportion of siponimod-treated patients with baseline EDSS of 6.5 (19.8% vs 26.1%) progressed to EDSS ≥7 (36% risk reduction; HR [95% CI]: 0.64 [0.41; 1.0]; p=0.0483). In the multistate model, siponimod-treated patients had a 21% risk reduction (HR [95% CI]: 0.79 [0.63; 1.00]) of transitioning from EDSS ≤5 to EDSS 5.5-6, and a 28% risk reduction (HR [95% CI]: 0.72 [0.48; 1.06]) of transitioning from EDSS 6.5 to sustained EDSS ≥7. Under the assumption of the model (stable effect over time), compared to placebo, siponimod extended the median time to EDSS ≥7 by 4.3 years in the overall population (12.0 years vs 16.3 years).
Conclusion: The post hoc analyses suggest that siponimod delayed time to wheelchair dependence, further supporting the clinical relevance of the effect of siponimod on delaying physical disability progression in patients with SPMS.
Disclosure: Patrick Vermersch has received honoraria and consulting fees from Biogen, Sanofi, Teva, Novartis, Merck and Almirall, and research support from Biogen, Sanofi, Bayer, and Merck.
Ralf Gold has received compensation for serving as a consultant or speaker from Bayer HealthCare, Biogen, Merck, Novartis and Teva. He, or the institution he works for, has received research support from Bayer HealthCare, Biogen, Merck, Novartis and Teva; he has also received honoraria as a Journal Editor from SAGE and Thieme Verlag.
Ludwig Kappos' institution (University Hospital Basel) has received the following exclusively for research support: steering committee, advisory board and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen Idec, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB and Xenoport); speaker fees (Bayer HealthCare, Biogen Idec, Merck, Novartis, Sanofi and Teva); support for educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi and Teva); licence fees for Neurostatus products; and grants (Bayer HealthCare, Biogen Idec, European Union, INNO-Swiss, Merck, Novartis, Roche Research Foundation, Swiss MS Society and Swiss National Research Foundation).
Robert Fox has received compensation for serving as a consultant or speaker from Allozyne, Avanir, Biogen, Novartis, Questcor and Teva Pharmaceutical Industries. He, or the institution he works for, has received research support from Novartis.
Amit Bar-Or has participated as a speaker in meetings sponsored by and received consulting fees and/or grant support from: Atara Biotherapeutics, Biogen Idec, Celgene/Receptos, Genentech/Roche, GlaxoSmithKline, MAPI, MedImmune, Merck/EMD Serono, Novartis and Sanofi Genzyme.
Bruce A.C. Cree has received personal compensation for consulting from Abbvie, Akili, Alexion, Biogen, EMD Serono, Novartis, Sanofi Genzyme and TG Therapeutics.
Gavin Giovannoni is a steering committee member on the daclizumab trials for AbbVie, the BG12 and daclizumab trials for Biogen, the fingolimod and siponimod trials for Novartis, the laquinimod trials for Teva and the ocrelizumab trials for Roche. He has also received consultancy fees for advisory board meetings for oral cladribine trials for Merck KGaA, Sanofi Genzyme, and in relation to DSMB activities for Synthon BV, as well as honoraria for speaking at the Physicians' summit and several medical education meetings. He is also the Co-Chief Editor of Multiple Sclerosis and Related Disorders (Elsevier).
Nicolas Rouyrre, Sophie Arnould, Frank Dahlke, and Goeril Karlsson are employees of Novartis.
This study was funded by Novartis Pharma AG, Basel, Switzerland

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