Abstract

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing–remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.

Highlights

  • Multiple sclerosis (MS) is one of the most prevalent and disabling neurologic conditions worldwide

  • The mean cumulative number of gadolinium-enhancing lesions on Magnetic resonance imaging (MRI) was reduced with both doses of ozanimod: 1.5 with ozanimod 0.5 mg and 1.5 with ozanimod 1 mg versus 11.1 with placebo

  • As in the RADIANCE phase III trial, this study reported a reduction in the loss of whole-brain volume, cortical grey matter, and thalamic volume with ozanimod when compared to interferon beta-1a

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Summary

Introduction

Multiple sclerosis (MS) is one of the most prevalent and disabling neurologic conditions worldwide. Multiple sclerosis is classified into clinically isolated syndrome (CIS), relapsing–remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS) and progressive relapsing MS (PRMS) based on the clinical course of disease [6]. The disease pathology begins when autoreactive T-cells cross the blood-brain barrier (BBB) and induce inflammation These CD8+ T-cells secrete pro-inflammatory cytokines and aid in the activation and recruitment of other immune cells, including B-cells, macrophages, microglia, astrocytes, and plasma cells [6]. The currently approved pharmacologic options have demonstrated efficacy in managing and slowing the disease, they are associated with greater risks and non-compliance due to side effect profiles [4] This emphasizes the continued need for novel medications with high safety profiles, those that target MS early in its course to mitigate disease progression and improve quality of life

Multiple Sclerosis Epidemiology
Risk Factors
Pathophysiology
Presentation
Current Treatment of Multiple Sclerosis
Management of Relapses
DMTs: Self-Injected
DMTs: Oral
Neuromodulation
Ozanimod Drug Information
Ozanimod Mechanism of Action
Absorption and Distribution
Metabolism
Elimination
10. Pharmacodynamics
Results and Findings
Conclusions
11.1. Phase I Studies
11.2. Phase II Studies
11.3. Phase III Studies
11.4. Phase III Studies
11.5. Additional Studies
12. Conclusions
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