Siponimod: A Review in Secondary Progressive Multiple Sclerosis

CNS Drugs, Год журнала: 2020, Номер 34(11), С. 1191 - 1200

Опубликована: Окт. 27, 2020

Oral siponimod (Mayzent®), a next-generation, selective sphingosine 1-phosphate receptor (S1PR) 1 and 5 modulator, is approved in several countries for the treatment of secondary progressive multiple sclerosis (SPMS), with specific indications varying between individual countries. In pivotal EXPAND trial (median duration double-blind 18 months) broad spectrum patients SPMS, once-daily oral 2 mg (initial dose titration over 6 days) was significantly more effective than placebo reducing clinical MRI-defined outcomes disease activity disability progression, including 3-month confirmed progression on Expanded Disability Status Scale (EDSS), generally well tolerated core phase study. These beneficial effects appeared to be sustained during up years ongoing open-label extension EXPAND. The safety profile similar that other agents its class, adverse events special interest (i.e. those known associated S1PR modulators). No new signals were identified years' phase. Albeit further long-term efficacy data from real-world setting are required fully define role, given paucity current options convenient dosage regimen, represents an important emerging option adult SPMS active evidenced by relapses or imaging-features inflammatory activity.

Язык: Английский

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Clinical and Paraclinical Biomarkers and the Hitches to Assess Conversion to Secondary Progressive Multiple Sclerosis: A Systematic Review

Frontiers in Neurology, Год журнала: 2021, Номер 12

Опубликована: Авг. 26, 2021

Conversion to secondary progressive (SP) course is the decisive factor for long-term prognosis in relapsing multiple sclerosis (MS), generally considered clinical equivalent of MS-associated neuroaxonal degeneration. Evidence accumulating that both inflammation and neurodegeneration are present along a continuum pathologic processes all phases MS. While prominent feature early stages, its quality changes relative importance disease decreases while neurodegenerative prevail with ongoing disease. Consequently, anti-inflammatory disease-modifying therapies successfully used MS ineffective SPMS, whereas specific treatment latter increasingly focus research. Therefore, prevention, but also (anticipatory) diagnosis crucial importance. The problem currently SPMS exclusively based on retrospectively assessing increase overt physical disability usually over past 6–12 months. This inevitably results delay up 3 years resulting periods uncertainty and, thus, making therapy adaptation prevent conversion impossible. Hence, there an urgent need reliable objective biomarkers prospectively predict define conversion. Here, we review current evidence parameters, magnetic resonance imaging optical coherence tomography measures, serum cerebrospinal fluid context Ultimately, discuss necessity multimodal approaches order approach definition prediction SPMS.

Язык: Английский

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Recent advances in the treatment of primary and secondary progressive Multiple Sclerosis

Journal of Neuroimmunology, Год журнала: 2024, Номер 390, С. 578315 - 578315

Опубликована: Фев. 17, 2024

Язык: Английский

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Should We Use Clinical Tools to Identify Disease Progression?

Frontiers in Neurology, Год журнала: 2021, Номер 11

Опубликована: Янв. 21, 2021

The presence of disability progression in multiple sclerosis (MS) is an important hallmark for MS patients the course their disease. transition from relapsing remitting (RRMS) to secondary progressive forms disease (SPMS) represents a significant change quality life and perception It could also be therapeutic key opportunities, where approaches different those initial phases can adopted. characterization structural biomarkers (e.g., magnetic resonance imaging or neurofilament light chain) has been proposed differentiate between both phenotypes. However, there no definite threshold them. Whether risk clinical predicted by markers at early still focus research. several theories pathological evidence suggest that phenotypes are part continuum with common pathophysiological mechanisms. In this case, evaluation would play preponderant role above destruction identification SPMS. For purpose, use tools beyond Expanded Disability Status Scale (EDSS) should considered. Besides established functional tests such as Multiple Sclerosis Functional Composite (MSFC), patient's neurological history digital resources may help neurologists decision-taking. article, we discuss arguments detection activity.

Язык: Английский

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Pharmacogenetics of siponimod: A systematic review

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 153, С. 113536 - 113536

Опубликована: Авг. 12, 2022

Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) the first oral treatment option for adult patients with secondary progressive multiple sclerosis. We performed systematic review of pharmacogenetics Siponimod, we found that (430 C>T; rs1799853) CYP2C9 * 3 (1075 A>C; rs1057910), both translated no-function alleles, have been related to lower metabolism by enzyme. The FDA-approved drug label EMA risk management plan require testing genotype before starts. FDA states contraindicated in carrying 3/* genotype, daily maintenance dose 1 mg 1/* 2/* genotypes. reported potential long-term safety implications poor metabolizer treated this drug. Based on concluded SNPs influence response might be stated assessing not only 2 but other genetic variants resulting IM/PM status. IM phenotype from should revised since it contradictory compared excluded PGx recommendation starts into therapeutic recommendation.

Язык: Английский

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Multiple Sclerosis Progression Discussion Tool Usability and Usefulness in Clinical Practice: Cross-sectional, Web-Based Survey

Journal of Medical Internet Research, Год журнала: 2021, Номер 23(10), С. e29558 - e29558

Опубликована: Июль 27, 2021

A digital tool, Multiple Sclerosis Progression Discussion Tool (MSProDiscuss), was developed to facilitate discussions between health care professionals (HCPs) and patients in evaluating early, subtle signs of multiple sclerosis (MS) disease progression.The aim this study is report the findings on usability usefulness MSProDiscuss a real-world clinical setting.In cross-sectional, web-based survey, HCPs across 34 countries completed an initial individual questionnaire (comprising 7 questions comprehensibility, usability, after using during each patient consultation) final 13 usefulness, integration adoption into practice capture HCPs' overall experience tool). The responses were provided 5-point Likert scale. All analyses descriptive, no statistical comparisons made.In total, 301 tested tool 6974 people with MS, whom 77% (5370/6974) had relapsing-remitting including those suspected be transitioning secondary progressive MS. time taken complete reported range 1 4 minutes 97.3% (6786/6974; initial) 98.2% (269/274; final) cases. In 93.54% (6524/6974; 97.1% (266/274; cases, agreed (4 or 5 scale) that able comprehend tool. willing use again same patient, 90.47% (6310/6974; useful discussing MS symptoms their impact daily activities (6121/6974, 87.76% 252/274, 92% cognitive function (5482/6974, 78.61% 271/274, 79.2% final), as well progression general (6102/6974, 87.49% 246/274, 89.8% final). While completing questionnaire, 94.9% (260/274) similar asked regular consultation, helped better understand (249/274, 90.9%) (220/274, 80.3%). Overall, (252/274) they would recommend colleague, 85.8% (235/274) integrate it practice.MSProDiscuss usable physician-patient discussion practice. Most easy

Язык: Английский

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MSProDiscuss™ Clinical Decision Support Tool for Identifying Multiple Sclerosis Progression

Journal of Clinical Medicine, Год журнала: 2022, Номер 11(15), С. 4401 - 4401

Опубликована: Июль 28, 2022

This article describes the rationale for development of MSProDiscuss™ clinical decision support (CDS) tool, its development, and insights into how it can help neurologists improve care patients with multiple sclerosis (MS). MS is a progressive disease characterized by heterogeneous symptoms variable course. There growing consensus that exists on continuum, overlap between relapsing-remitting secondary phenotypes. Evidence demonstrates neuroaxonal loss occurs from outset, progression occur independent relapse activity, continuous underlying pathological processes may not be reflected inflammatory activity indicative patient's immune response. Early intervention benefit patients, there need tool assists physicians in rapidly identifying subtle signs progression. MSProDiscuss, developed facilitates structured approach to patient consultations. It analyzes multidimensional data via an algorithm estimate likelihood (the MSProDiscuss score), contribution various symptoms, impact daily living, enabling more personalized treatment management. Data CDS tools such as offer new course facilitate informed decision-making holistic care.

Язык: Английский

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Clinical Evaluation of Siponimod for the Treatment of Secondary Progressive Multiple Sclerosis: Pathophysiology, Efficacy, Safety, Patient Acceptability and Adherence

Patient Preference and Adherence, Год журнала: 2022, Номер Volume 16, С. 1307 - 1319

Опубликована: Май 1, 2022

Introduction: A number of disease-modifying therapies have been approved for use in relapsing-remitting multiple sclerosis (MS) the past two decades. However, only few treatment options are available patients with secondary progressive (SPMS). Siponimod has recently active forms SPMS (who experience clinical relapses or new lesions on MRI superimposed progression independent relapse activity). Objective: The aim this article is to provide a comprehensive review mechanism action, efficacy, safety, cost effectiveness and patient adherence siponimod. Methods: We performed PubMed search using terms: "siponimod", "secondary sclerosis", "sphingosine 1-phosphate modulators". Titles abstract were screened selected relevance key section article. Findings: an oral sphingosine-1-phosphate receptor (S1PR) modulator selectivity S1PR-1 5. Modulation lymphocytes causes its internalization degradation, preventing their egress from lymphoid tissues blood. In pivotal Phase 3 randomized controlled trial EXPAND, siponimod was superior placebo reducing risk disability confirmed at 6 months, as well development rate brain volume loss. Secondary analysis also showed benefit measures cognitive functioning. lymphopenia first-dose bradycardia appears be lower compared non-selective S1P1R modulators. Different CYP2C9 genotypes affect metabolism siponimod; hence, genetic testing required adapt titration final dose accordingly. Conclusion: Long-term extension real-world studies will allow further evaluation efficacy safety population. Future research should focus better defining SPMS, identifying biomarkers outcome response category patients. Keywords: sclerosis, siponimod,

Язык: Английский

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OzEAN Study to Collect Real-World Evidence of Persistent Use, Effectiveness, and Safety of Ozanimod Over 5 Years in Patients With Relapsing-Remitting Multiple Sclerosis in Germany

Frontiers in Neurology, Год журнала: 2022, Номер 13

Опубликована: Июнь 27, 2022

Ozanimod, a sphingosine 1-phosphate receptor 1 and 5 modulator, was approved as disease-modifying therapy for active relapsing-remitting multiple sclerosis (RRMS) in 2020 ulcerative colitis 2021. Long-term, real-world studies nonselective population are needed. OzEAN is an ongoing study to assess the persistent use, effectiveness, safety of ozanimod its impact on quality life (QoL) patients with RRMS over 5-year period.This prospective, noninterventional, postmarketing authorization will enroll ~1,300 (≥18 years age) RRMS. The decision initiate must have been made before independent from participation. Enrollment began March Recruitment last 36 months across 140 sites Germany. Treatment-naive or those having prior experience receive oral 0.92 mg/day after initial dose escalation, per summary product characteristics recommendations, up 60 months. Persistence treatment (primary endpoint) assessed at month 60. Secondary endpoints include additional physician-reported outcomes [persistence earlier time points, annualized relapse rate, Expanded Disability Status Scale score, cognition (Symbol Digit Modalities Test), incidence adverse events], patient-reported assessing patient satisfaction, adherence, modalities (Treatment Satisfaction Questionnaire Medication, v1.4), disability (United Kingdom Neurological Rating Scale), QoL (MSQOL-54 questionnaire), fatigue (Fatigue Motor Cognitive Functions), health economics [Work Productivity Activity Impairment Multiple Sclerosis (German v2.1); Health Resource Survey, v3.0]. A Documentation System internet-based e-health portal allows view files complete questionnaires. follow-up occur 3-8 who discontinue early. Long-term results anticipated completion 2029. Yearly interim analyses planned enrollment has reached 25%.This first long-term, and, our knowledge, noninterventional utilizing portal. These data add safety/efficacy profile demonstrated phase 3 trials.Clinicaltrials.gov, identifier: NCT05335031.

Язык: Английский

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The transitional phase of multiple sclerosis: The concept of PANGAEA 2.0 evolution study

Multiple Sclerosis and Related Disorders, Год журнала: 2020, Номер 46, С. 102523 - 102523

Опубликована: Сен. 19, 2020

Язык: Английский

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