Effect of Sphingosine 1 Phosphate Receptor Modulators on Fatigue Among Multiple Sclerosis Patients
Mahmoud Elkhooly1, Muhammad Ismail2, Fen Bao3, Shashi Maryala1, Evanthia Bernitsas4
1Department of Neurology, Southern Illinois University School of medicine, Springfield, IL, USA, 2Department of Neurology, Minia University, Minia, Egypt, 3Wayne State School of Medicine, 4Creighton University School of Medicine, Omaha,NE, USA
Objective:

This study aims to explore the effect of Sphingosine 1-phosphate receptor modulators (S1PR) on fatigue in patients with multiple sclerosis (PwMS).

Background:

Fatigue is a common symptom among PwMS and affects 60-90% of patients. It is associated with a considerable impact on quality of life. Four S1PR (fingolimod, Siponimod, ozanimod and ponesimod) modulators were approved for Multiple Sclerosis (MS). They act by reducing the circulating lymphocyte through interference with the migration of the inflammatory cells to the CNS. Fatigue pathophysiology is poorly understood despite the advances in research. We aim to explore the impact of S1PR and fatigue.

Design/Methods:

A comprehensive analysis and literature search of PubMed, Google Scholar, and Scopus was conducted from December 1st, 2000, till October 10th, 2024. It included all the studies that studied the effect of S1PR on fatigue in patients with multiple sclerosis (PwMS). A meta-analysis was done using Reman software, and the effect size ( mean difference) was calculated. 

Results:

We found 5 studies, 3 of which were randomized to injectable DMT, Standard DMT (interferon and glatiramer acetate), and teriflunomide, respectively. A total of 1771 participants were analyzed, with 858 participants receiving fingolimod and 913 receiving ponesimod. Three studies on fingolimod and two on ponesimod. No studies examined the effects of ozanimod or Siponimod on fatigue. The overall mean difference favored S1PR modulators over the other DMT (MD -3.57. 95% CI -5.69 to -1.45). Pooled studies were homogenous (P= .18, I-square = 38%).

Conclusions:

Fingolimod and ponesimod were found to be effective in improving fatigue among PwMS; no studies have been found on ozanimod and Siponimod. As fatigue has a complex and subjective nature, more studies are required. 

10.1212/WNL.0000000000212658
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