Effects of siponimod: A Synthesis of Findings from 19 Studies

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Original Abstract of the Article

Major Research Findings

Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator, already approved for the treatment of multiple sclerosis. 8 , 19 , 13 , 10 , 3 , 9 , 6 , 5 , 14 , 7 , 18 , 4 , 2 , 11 , 1 These studies suggest that siponimod has potential for inhibiting ocular angiogenesis and could be helpful in treating diseases associated with ocular neovascularization. 8 Siponimod inhibited retinal endothelial cell migration, enhanced endothelial barrier function, protected against tumor necrosis factor alpha (TNF-α)-induced barrier disruption, and also inhibited suture-induced corneal neovascularization in rabbits. 8 However, siponimod was associated with delayed onset bilateral cystoid macular edema in a patient with stable proliferative diabetic retinopathy. 17 Siponimod showed neuroprotective effects and attenuated apoptosis of retinal ganglion cells in a mouse model of glaucoma. 15 Furthermore, siponimod ameliorated metabolic oligodendrocyte injury and modulated microglia activation in a mouse model of multiple sclerosis. 19 , 13 In addition, siponimod demonstrated promising potential as a therapeutic strategy for stroke in a mouse model of brain ischemia. 7

Benefits and Risks

Benefit Summary

Siponimod could potentially be useful in treating diseases associated with ocular neovascularization due to its ability to inhibit ocular angiogenesis. 8 Siponimod also showed neuroprotective effects and attenuated apoptosis of retinal ganglion cells in a mouse model of glaucoma. 15 Additionally, siponimod ameliorated metabolic oligodendrocyte injury and modulated microglia activation in a mouse model of multiple sclerosis. 19 , 13 Siponimod demonstrated promising potential as a therapeutic strategy for stroke in a mouse model of brain ischemia. 7

Risk Summary

Siponimod was associated with delayed onset bilateral cystoid macular edema in a patient with stable proliferative diabetic retinopathy. 17 Siponimod might promote melanoma proliferation. 14 Furthermore, like other immunotherapies, siponimod can cause various adverse effects. 1

Comparison Between Studies

Commonalities

The studies suggest that siponimod is a promising drug for treating diseases like multiple sclerosis and ocular neovascularization. 8 , 19 , 13 , 10 , 3 , 9 , 6 , 5 , 14 , 7 , 18 , 4 , 2 , 11 , 1

Differences

These studies illuminate various aspects of siponimod's mechanism of action and efficacy. 8 , 19 , 13 , 10 , 3 , 9 , 6 , 5 , 14 , 7 , 18 , 4 , 2 , 11 , 1

Consistency and Contradictions in Results

Siponimod appears to have potential for inhibiting ocular angiogenesis and is suggested to be effective in treating multiple sclerosis. 8 , 19 , 13 , 10 , 3 , 9 , 6 , 5 However, there is a study suggesting that siponimod could promote melanoma proliferation. 14 Additionally, siponimod, like other immunotherapies, can cause various adverse effects. 1

Precautions for Applying Research Findings to Everyday Life

Siponimod could potentially be helpful in treating diseases associated with ocular neovascularization and multiple sclerosis. 8 , 19 , 13 , 10 , 3 , 9 , 6 , 5 However, keep in mind that siponimod might promote melanoma proliferation and can cause various adverse effects. 14 , 1 Therefore, it is crucial to consult with your doctor before taking siponimod and carefully monitor your health while taking it. 17

Limitations of Current Research

These studies suggest that more research is necessary to fully understand the effects of siponimod. 8 , 19 , 13 , 10 , 3 , 9 , 6 , 5 , 14 , 7 , 18 , 4 , 2 , 11 , 1

Future Research Directions

Further research is essential for better understanding the mechanisms of action and safety of siponimod. 8 , 19 , 13 , 10 , 3 , 9 , 6 , 5 , 14 , 7 , 18 , 4 , 2 , 11 , 1

Conclusion

Siponimod is a drug that could potentially inhibit ocular angiogenesis and be helpful in treating multiple sclerosis. 8 , 19 , 13 , 10 , 3 , 9 , 6 , 5 However, it is important to be aware that siponimod could promote melanoma proliferation and can cause various adverse effects. 14 , 1 It is crucial to consult with your doctor before taking siponimod and carefully monitor your health while taking it. 17

Literature analysis of 19 papers
Positive Content
16
Neutral Content
2
Negative Content
1
Article Type
1
1
1
6
19
1.

Adverse effects of immunotherapies for multiple sclerosis: a network meta-analysis.

Author: TramacereIrene, VirgiliGianni, PerducaVittorio, LucenteforteErsilia, BenedettiMaria Donata, CapobussiMatteo, CastelliniGreta, FrauSerena, Gonzalez-LorenzoMarien, FeatherstoneRobin, FilippiniGraziella

Decreased disease activity
MS treatment
Safety uncertainty
Significant disability

Multiple sclerosis (MS) is a disease affecting the brain and spinal cord, primarily affecting young adults, with women being affected more often than men. While treatments for MS can slow the disease's progression, there's still uncertainty about their safety.

Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

The Benefits and Risks of Switching from Fingolimod to Siponimod for the Treatment of Relapsing-Remitting and Secondary Progressive Multiple Sclerosis.

Author: VališMartin, AchironAnat, HartungHans Peter, MarešJan, TicháVeronika, ŠtouračPavel, HaluskováSimona, AngelucciFrancesco, PavelekZbyšek

Slows disease progression

Fingolimod and siponimod, both S1P receptor modulators, have comparable therapeutic effects in slowing the progression of multiple sclerosis (MS), although fingolimod is primarily used for relapsing-remitting MS (RRMS) and siponimod for active secondary progressive MS (SPMS). Clinicians are currently evaluating the potential benefits and risks of switching patients from fingolimod to siponimod.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

5.

Current Status of Oral Disease-Modifying Treatment Effects on Cognitive Outcomes in Multiple Sclerosis: A Scoping Review.

Author: CarlomagnoVincenzo, MirabellaMassimiliano, LucchiniMatteo

Cognitive impairment treatment

This review examines the current evidence on the effects of oral disease-modifying treatments (DMTs) on cognitive function in patients with multiple sclerosis (MS). The review highlights the need for standardized cognitive evaluations and further research to understand the impact of DMTs on cognitive outcomes.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

6.

Central Versus Peripheral Drug Exposure Ratio, a Key Differentiator for Siponimod Over Fingolimod?

Author: BigaudMarc, RamseierPamela, TisserandSarah, LangMeike, UrbanBeatrice, BeerliChristian, KarlssonGöril

Disability progression control
Multiple sclerosis treatment
None

Siponimod is a medication used to treat multiple sclerosis. This abstract describes the unique efficacy of siponimod in treating secondary progressive multiple sclerosis (SPMS) compared to other medications, such as fingolimod.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

9.

Molecular and neuroimmune pharmacology of S1P receptor modulators and other disease-modifying therapies for multiple sclerosis.

Author: KiharaYasuyuki, ChunJerold

MS treatment

This review summarizes the currently approved disease-modifying therapies (DMTs) for multiple sclerosis (MS) and provides details on the molecular pharmacology, immunopharmacology, and neuropharmacology of sphingosine 1-phosphate (S1P) receptor (S1PR) modulators. It highlights the CNS-oriented, astrocyte-centric mechanism of action of fingolimod, a S1PR modulator, suggesting a potential dual role in reducing both inflammation and neurodegeneration in MS.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

10.

An update on the use of sphingosine 1-phosphate receptor modulators for the treatment of relapsing multiple sclerosis.

Author: DumitrescuLaura, PapathanasiouAthanasios, CoclituCatalina, GarjaniAfagh, EvangelouNikos, ConstantinescuCris S, PopescuBogdan Ovidiu, TanasescuRadu

Relapsing MS treatment
Interfere with function

Sphingosine-1-phosphate-receptor (S1PR) modulators are oral disease-modifying therapies for relapsing multiple sclerosis (MS). These drugs work by binding to the lymphocytic S1P-subtype-1-receptor, preventing lymphocyte egress from lymph nodes. They may also interfere with other biological functions.

ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

12.

A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study.

Author: SwenJesse J, van der WoudenCathelijne H, MansonLisanne En, Abdullah-KoolmeesHeshu, BlagecKathrin, BlagusTanja, BöhringerStefan, Cambon-ThomsenAnne, CecchinErika, CheungKa-Chun, DeneerVera Hm, DupuiMathilde, Ingelman-SundbergMagnus, JonssonSiv, Joefield-RokaCandace, JustKatja S, KarlssonMats O, KontaLidija, KoopmannRudolf, KriekMarjolein, LehrThorsten, MitropoulouChristina, Rial-SebbagEmmanuelle, RollinsonVictoria, RoncatoRossana, SamwaldMatthias, SchaeffelerElke, SkokouMaria, SchwabMatthias, SteinbergerDaniela, StinglJulia C, TremmelRoman, TurnerRichard M, van RhenenMandy H, Dávila FajardoCristina L, DolžanVita, PatrinosGeorge P, PirmohamedMunir, Sunder-PlassmannGere, ToffoliGiuseppe, GuchelaarHenk-Jan,

Safer drug therapy
Adverse drug reaction

A cluster-randomized crossover study of 6944 patients in Europe found that genotype-guided treatment using a 12-gene pharmacogenetic panel significantly reduced the incidence of clinically relevant adverse drug reactions. In patients with an actionable test result, the odds ratio (OR) for clinically relevant adverse drug reactions was 0.70, indicating a 30% reduction in the study group compared to the control group. The study demonstrated that this approach is feasible across diverse European healthcare settings.

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

15.

S1PR1 signaling attenuates apoptosis of retinal ganglion cells via modulation of cJun/Bim cascade and Bad phosphorylation in a mouse model of glaucoma.

Author: BasavarajappaDevaraj, GuptaVivek, WallRoshana Vander, GuptaVeer, ChitranshiNitin, MirshahvaladiSeyed Shahab Oddin, PalanivelViswanthram, YouYuyi, MirzaeiMehdi, KlistornerAlexander, GrahamStuart L

Neuroprotection

This study investigated the neuroprotective role of the sphingosine 1-phosphate receptor 1 (S1PR1) in glaucoma. The findings indicate that activation of S1PR1 via siponimod treatment significantly reduced retinal ganglion cell (RGC) death by promoting neuroprotective signaling pathways and inhibiting apoptosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis.

Author: WeierAlicia, EndersMichael, KirchnerPhilipp, EkiciArif, BigaudMarc, KapitzaChristopher, WörlJürgen, KuertenStefanie

Reduced brain atrophy
Reduced disease progression

This study investigated the effects of siponimod on the enteric nervous system and central nervous system in an experimental autoimmune encephalomyelitis model of multiple sclerosis.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

Siponimod-related bilateral cystoid macular oedema and intravenous fluorescein angiographic findings in a patient with stable proliferative diabetic retinopathy without history of diabetic macular oedema.

Author: FoosWilliam F, CulpCatherine, AsahiMasumi, PatronasMarena

Siponimod macular edema

This case report describes delayed onset bilateral cystoid macular oedema in a patient with stable proliferative diabetic retinopathy who developed the condition after starting siponimod treatment. Similar to FAME (fingolimod-associated macular oedema), the cystoid macular oedema resolved with drug cessation and topical anti-inflammatory therapy.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

18.

[Progressive Multifocal Leukoencephalopathy: An Overview of Current Topics].

Author: YukitakeMotohiro

MS treatment
PML

This study reviews the current status of progressive multifocal leukoencephalopathy (PML) associated with disease-modifying drugs (DMDs) for multiple sclerosis (MS). It discusses the possibility of PML onset with newly proposed DMDs, siponimod and ofatumumab, and highlights the importance of PML treatment in the era of DMD-associated PML.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : Japanese

19.

Siponimod ameliorates metabolic oligodendrocyte injury via the sphingosine-1 phosphate receptor 5.

Author: BehrangiNewshan, HeinigLeo, FrintropLinda, SantrauEmily, KurthJens, KrauseBernd, AtanasovaDimitrinka, ClarnerTim, FragoulisAthanassios, JokschMarkus, RudolfHenrik, MeuthSven G, JoostSarah, KippMarkus

Oligodendrocyte protection
SPMS treatment
Siponimod efficacy

Siponimod, a sphingosine-1 phosphate receptor modulator, protects against damage to the central nervous system in a mouse model of multiple sclerosis. It was found to protect against degeneration of oligodendrocytes, demyelination, and axonal injury. The protective effects were independent of T and B cell modulation and were dependent on the S1PR5 receptor. This suggests that siponimod may be a promising treatment for multiple sclerosis and other neurodegenerative diseases.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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