Fingolimod 250microgram capsules

BACKGROUND: Sphingosine-1-phosphate receptor modulators (S1PRM) are used to treat relapsing multiple sclerosis (MS). Each drug has a different S1PR-subtype selectivity. They target the G-protein coupled S1P receptors and exert significant immunomodulatory effects, such as preventing the formation of new CNS lesions and the reactivation of pre-existing lesions. OBJECTIVE: This study aims to explore the efficacy and safety of S1PRM in treating MS. METHODS: A systematic literature search of PubMed, Embase, and Cochrane databases was conducted in August 2024. Randomized Controlled Trials that evaluated the efficacy of S1PRM in patients with MS were included. Changes in Annualized Relapse Rate and incidence of adverse effects were chosen as primary outcomes. Standardized mean differences (SMD) and odds ratio (OR) were calculated. Confidence interval was kept at 95%. Individual interventions were compared using the Surface Under Cumulative Ranking Curve (SUCRA). The risk of bias was assessed by the Cochrane risk-of-bias tool for randomized trials (RoB 2). RESULTS: The search query resulted in a total of 1750 studies. After screening, 17 studies were included in the final analysis, with a population of 16,006. Fingolimod (1.25 mg) was significantly associated with a decreased ARR (SMD = -0.4422, 95% CI = [-0.5450 to -0.3394], p-value < 0.0001, SUCRA = 92.65%). Whereas, ozanimod (1 mg) was associated with the lowest number of new Gadolinium-enhanced lesions (SMD = -0.6516, 95% CI = [-0.8944 to -0.4087], p-value < 0.0001, SUCRA = 86.38%). Siponimod (1.25 mg) was associated with the least number of adverse events (OR = 0.4606, 95% CI = [0.1893 to 1.1205], p = 0.0874, SUCRA = 93.20%). Almost all of the studies had a low risk of bias. CONCLUSION: Fingolimod (1.25 mg) and ozanimod (1 mg) had the best efficacy, and siponimod (1.25 mg and 0.25 mg) had the best safety profile among the S1PRM. Further longitudinal studies should be conducted to assess the long-term effects of these drugs on patient-reported outcomes.

Abstract licence: CC BY

Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects the central nervous system (CNS). Currently, MS treatment is limited to several Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved medications that slow disease progression by immunomodulatory action. Fingolimod and siponimod have similar mechanisms of action, and consequently, their therapeutic effects may be comparable. However, while fingolimod is mainly used for relapsing-remitting MS (RRMS), siponimod, according to EMA label, is recommended for active secondary progressive MS (SPMS). Clinicians and scientists are analysing whether patients can switch from fingolimod to siponimod and identifying the advantages or disadvantages of such a switch from a therapeutic point of view. In this review, we aim to discuss the therapeutic effects of these two drugs and the advantages/disadvantages of switching treatment from fingolimod to siponimod in patients with the most common forms of MS, RRMS and SPMS.

Abstract licence: CC BY-NC

Fingolimod is a well-tolerated, highly effective disease-modifying therapy successfully utilized in the management of multiple sclerosis. The active metabolite, fingolimod-phosphate, acts on sphingosine-1-phosphate receptors (S1PRs) to bring about an array of pharmacological effects. While being initially recognized as a novel agent that can profoundly reduce T-cell numbers in circulation and the CNS, thereby suppressing inflammation and MS, there is now rapidly increasing knowledge on its previously unrecognized molecular and potential therapeutic effects in diverse pathological conditions. In addition to exerting inhibitory effects on sphingolipid pathway enzymes, fingolimod also inhibits histone deacetylases, transient receptor potential cation channel subfamily M member 7 (TRMP7), cytosolic phospholipase A2α (cPLA2α), reduces lysophosphatidic acid (LPA) plasma levels, and activates protein phosphatase 2A (PP2A). Furthermore, fingolimod induces apoptosis, autophagy, cell cycle arrest, epigenetic regulations, macrophages M1/M2 shift and enhances BDNF expression. According to recent evidence, fingolimod modulates a range of other molecular pathways deeply rooted in disease initiation or progression. Experimental reports have firmly associated the drug with potentially beneficial therapeutic effects in immunomodulatory diseases, CNS injuries, and diseases including Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, and even cancer. Attractive pharmacological effects, relative safety, favorable pharmacokinetics, and positive experimental data have collectively led to its testing in clinical trials. Based on the recent reports, fingolimod may soon find its way as an adjunct therapy in various disparate pathological conditions. This review summarizes the up-to-date knowledge about molecular pharmacology and potential therapeutic uses of fingolimod.

Abstract licence: CC BY