Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study

Background Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of...

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Veröffentlicht in:Journal of neurology Jg. 269; H. 9; S. 5093 - 5104
Hauptverfasser: Gold, Ralf, Piani-Meier, Daniela, Kappos, Ludwig, Bar-Or, Amit, Vermersch, Patrick, Giovannoni, Gavin, Fox, Robert J., Arnold, Douglas L., Benedict, Ralph H. B., Penner, Iris-Katharina, Rouyrre, Nicolas, Kilaru, Ajay, Karlsson, Göril, Ritter, Shannon, Dahlke, Frank, Hach, Thomas, Cree, Bruce A. C.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2022
Springer Nature B.V
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ISSN:0340-5354, 1432-1459, 1432-1459
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Abstract Background Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS. Methods Post hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND. Endpoints: 3-month/6-month confirmed disability progression (3mCDP/6mCDP); 3-month confirmed ≥ 20% worsening in Timed 25-Foot Walk (T25FW); 6-month confirmed improvement/worsening in Symbol Digit Modalities Test (SDMT) scores (≥ 4-point change); T2 lesion volume (T2LV) change from baseline; number of T1 Gd + lesions baseline–month 24; number of new/enlarging (N/E) T2 lesions over all visits. Results Data from 779 participants with aSPMS were analysed. Siponimod reduced risk of 3mCDP/6mCDP vs placebo (by 31%/37%, respectively; p  < 0.01); there was no significant effect on T25FW. Siponimod increased likelihood of 6-month confirmed SDMT improvement vs placebo (by 62%; p  = 0.007) and reduced risk of 6-month confirmed SDMT worsening (by 27%; p  = 0.060). Siponimod was associated with less increase in T2LV (1316.3 vs 13.3 mm 3 ; p  < 0.0001), and fewer T1 Gd + and N/E T2 lesions than placebo (85% and 80% reductions, respectively; p  < 0.0001). Conclusions In aSPMS, siponimod reduced risk of disability progression and was associated with benefits on cognition and MRI outcomes vs placebo. Trial registration ClinicalTrials.gov number : NCT01665144.
AbstractList Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS. Post hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND. 3-month/6-month confirmed disability progression (3mCDP/6mCDP); 3-month confirmed ≥ 20% worsening in Timed 25-Foot Walk (T25FW); 6-month confirmed improvement/worsening in Symbol Digit Modalities Test (SDMT) scores (≥ 4-point change); T2 lesion volume (T2LV) change from baseline; number of T1 Gd + lesions baseline-month 24; number of new/enlarging (N/E) T2 lesions over all visits. Data from 779 participants with aSPMS were analysed. Siponimod reduced risk of 3mCDP/6mCDP vs placebo (by 31%/37%, respectively; p < 0.01); there was no significant effect on T25FW. Siponimod increased likelihood of 6-month confirmed SDMT improvement vs placebo (by 62%; p = 0.007) and reduced risk of 6-month confirmed SDMT worsening (by 27%; p = 0.060). Siponimod was associated with less increase in T2LV (1316.3 vs 13.3 mm ; p < 0.0001), and fewer T1 Gd + and N/E T2 lesions than placebo (85% and 80% reductions, respectively; p < 0.0001). In aSPMS, siponimod reduced risk of disability progression and was associated with benefits on cognition and MRI outcomes vs placebo. ClinicalTrials.gov number: NCT01665144.
Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS.BACKGROUNDSiponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS.Post hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND.METHODSPost hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND.3-month/6-month confirmed disability progression (3mCDP/6mCDP); 3-month confirmed ≥ 20% worsening in Timed 25-Foot Walk (T25FW); 6-month confirmed improvement/worsening in Symbol Digit Modalities Test (SDMT) scores (≥ 4-point change); T2 lesion volume (T2LV) change from baseline; number of T1 Gd + lesions baseline-month 24; number of new/enlarging (N/E) T2 lesions over all visits.ENDPOINTS3-month/6-month confirmed disability progression (3mCDP/6mCDP); 3-month confirmed ≥ 20% worsening in Timed 25-Foot Walk (T25FW); 6-month confirmed improvement/worsening in Symbol Digit Modalities Test (SDMT) scores (≥ 4-point change); T2 lesion volume (T2LV) change from baseline; number of T1 Gd + lesions baseline-month 24; number of new/enlarging (N/E) T2 lesions over all visits.Data from 779 participants with aSPMS were analysed. Siponimod reduced risk of 3mCDP/6mCDP vs placebo (by 31%/37%, respectively; p < 0.01); there was no significant effect on T25FW. Siponimod increased likelihood of 6-month confirmed SDMT improvement vs placebo (by 62%; p = 0.007) and reduced risk of 6-month confirmed SDMT worsening (by 27%; p = 0.060). Siponimod was associated with less increase in T2LV (1316.3 vs 13.3 mm3; p < 0.0001), and fewer T1 Gd + and N/E T2 lesions than placebo (85% and 80% reductions, respectively; p < 0.0001).RESULTSData from 779 participants with aSPMS were analysed. Siponimod reduced risk of 3mCDP/6mCDP vs placebo (by 31%/37%, respectively; p < 0.01); there was no significant effect on T25FW. Siponimod increased likelihood of 6-month confirmed SDMT improvement vs placebo (by 62%; p = 0.007) and reduced risk of 6-month confirmed SDMT worsening (by 27%; p = 0.060). Siponimod was associated with less increase in T2LV (1316.3 vs 13.3 mm3; p < 0.0001), and fewer T1 Gd + and N/E T2 lesions than placebo (85% and 80% reductions, respectively; p < 0.0001).In aSPMS, siponimod reduced risk of disability progression and was associated with benefits on cognition and MRI outcomes vs placebo.CONCLUSIONSIn aSPMS, siponimod reduced risk of disability progression and was associated with benefits on cognition and MRI outcomes vs placebo.ClinicalTrials.gov number: NCT01665144.TRIAL REGISTRATIONClinicalTrials.gov number: NCT01665144.
Background Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS. Methods Post hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND. Endpoints: 3-month/6-month confirmed disability progression (3mCDP/6mCDP); 3-month confirmed ≥ 20% worsening in Timed 25-Foot Walk (T25FW); 6-month confirmed improvement/worsening in Symbol Digit Modalities Test (SDMT) scores (≥ 4-point change); T2 lesion volume (T2LV) change from baseline; number of T1 Gd + lesions baseline–month 24; number of new/enlarging (N/E) T2 lesions over all visits. Results Data from 779 participants with aSPMS were analysed. Siponimod reduced risk of 3mCDP/6mCDP vs placebo (by 31%/37%, respectively; p  < 0.01); there was no significant effect on T25FW. Siponimod increased likelihood of 6-month confirmed SDMT improvement vs placebo (by 62%; p  = 0.007) and reduced risk of 6-month confirmed SDMT worsening (by 27%; p  = 0.060). Siponimod was associated with less increase in T2LV (1316.3 vs 13.3 mm 3 ; p  < 0.0001), and fewer T1 Gd + and N/E T2 lesions than placebo (85% and 80% reductions, respectively; p  < 0.0001). Conclusions In aSPMS, siponimod reduced risk of disability progression and was associated with benefits on cognition and MRI outcomes vs placebo. Trial registration ClinicalTrials.gov number : NCT01665144.
BackgroundSiponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however, phase 3 EXPAND study data are from an SPMS population with/without disease activity. A need exists to characterize efficacy/safety of siponimod in aSPMS.MethodsPost hoc analysis of participants with aSPMS (≥ 1 relapse in 2 years before study and/or ≥ 1 T1 gadolinium-enhancing [Gd +] magnetic resonance imaging [MRI] lesions at baseline) receiving oral siponimod (2 mg/day) or placebo for up to 3 years in EXPAND. Endpoints: 3-month/6-month confirmed disability progression (3mCDP/6mCDP); 3-month confirmed ≥ 20% worsening in Timed 25-Foot Walk (T25FW); 6-month confirmed improvement/worsening in Symbol Digit Modalities Test (SDMT) scores (≥ 4-point change); T2 lesion volume (T2LV) change from baseline; number of T1 Gd + lesions baseline–month 24; number of new/enlarging (N/E) T2 lesions over all visits.ResultsData from 779 participants with aSPMS were analysed. Siponimod reduced risk of 3mCDP/6mCDP vs placebo (by 31%/37%, respectively; p < 0.01); there was no significant effect on T25FW. Siponimod increased likelihood of 6-month confirmed SDMT improvement vs placebo (by 62%; p = 0.007) and reduced risk of 6-month confirmed SDMT worsening (by 27%; p = 0.060). Siponimod was associated with less increase in T2LV (1316.3 vs 13.3 mm3; p < 0.0001), and fewer T1 Gd + and N/E T2 lesions than placebo (85% and 80% reductions, respectively; p < 0.0001).ConclusionsIn aSPMS, siponimod reduced risk of disability progression and was associated with benefits on cognition and MRI outcomes vs placebo.Trial registrationClinicalTrials.gov number: NCT01665144.
Author Bar-Or, Amit
Fox, Robert J.
Benedict, Ralph H. B.
Vermersch, Patrick
Hach, Thomas
Rouyrre, Nicolas
Karlsson, Göril
Gold, Ralf
Dahlke, Frank
Kappos, Ludwig
Ritter, Shannon
Arnold, Douglas L.
Kilaru, Ajay
Cree, Bruce A. C.
Giovannoni, Gavin
Penner, Iris-Katharina
Piani-Meier, Daniela
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– sequence: 2
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  organization: Novartis Pharma AG
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  surname: Kappos
  fullname: Kappos, Ludwig
  organization: Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB) and Multiple Sclerosis Center, Departments of Head, Spine and Neuromedicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital, University of Basel
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  fullname: Arnold, Douglas L.
  organization: NeuroRx Research, Montreal, QC, Canada and Montreal Neurological Institute, McGill University
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  fullname: Penner, Iris-Katharina
  organization: Department of Neurology, Inselspital, Bern University Hospital, University of Bern
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  organization: Novartis Pharma AG
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  organization: Novartis Pharma AG
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  fullname: Karlsson, Göril
  organization: Novartis Pharma AG
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  surname: Cree
  fullname: Cree, Bruce A. C.
  organization: UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35639197$$D View this record in MEDLINE/PubMed
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ISSN 0340-5354
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Issue 9
Keywords EXPAND
Active secondary progressive multiple sclerosis
Disability progression
Cognition
Siponimod
MRI
Language English
License 2022. The Author(s).
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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SSID ssj0008459
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Snippet Background Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries;...
Siponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries; however,...
BackgroundSiponimod is a sphingosine 1-phosphate receptor modulator approved for active secondary progressive multiple sclerosis (aSPMS) in most countries;...
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StartPage 5093
SubjectTerms Azetidines - pharmacology
Azetidines - therapeutic use
Benzyl Compounds - pharmacology
Benzyl Compounds - therapeutic use
Cognition
Disease Progression
Gadolinium
Humans
Lesions
Magnetic Resonance Imaging
Medicine
Medicine & Public Health
Multiple sclerosis
Multiple Sclerosis - drug therapy
Multiple Sclerosis, Chronic Progressive - diagnostic imaging
Multiple Sclerosis, Chronic Progressive - drug therapy
Multiple Sclerosis, Relapsing-Remitting - drug therapy
NCT
NCT01665144
Neurology
Neuroradiology
Neurosciences
Original Communication
Placebos
Sphingosine 1-phosphate
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Title Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study
URI https://link.springer.com/article/10.1007/s00415-022-11166-z
https://www.ncbi.nlm.nih.gov/pubmed/35639197
https://www.proquest.com/docview/2700156432
https://www.proquest.com/docview/2672322600
https://pubmed.ncbi.nlm.nih.gov/PMC9363350
Volume 269
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