The efficacy and safety of fingolimod plus standardized treatment versus standardized treatment alone for acute ischemic stroke: A systematic review and meta‐analysis

Abstract

Acute ischemic stroke (AIS) is the most common type of stroke. Fingolimod is a sphingosine analog that acts on sphingosine‐1‐phosphate receptors (S1PR). Recently, the safety and efficacy of fingolimod in both patients with intracerebral hemorrhage and patients with AIS have been investigated in proof‐of‐concept trials. In this review, we performed a meta‐analysis to evaluate the efficacy and safety of fingolimod for AIS. This study was conducted according to the PRISMA (Preferred Reporting Items for Systemic review and Meta‐Analysis) statement. We searched for publications on the PubMed, Embase, Cochrane Central Register of Controlled Trials, Clinical trials, CNKI, Wanfang Data, VIP, CBM up to August 2021. We compiled five studies; a main meta‐analysis forest plots were conducted for the values of the proportion of patients whose modified Rankin scale (MRS) score was 0–1 at day 90. There were heterogeneities in each study; the method of sensitivity analysis was performed. A sensitivity analysis was performed with a mean difference (MD) of the efficacy of fingolimod plus standardized treatment versus standardized treatment alone. Random effect model is used for meta‐analysis regardless of the I2 index. The analysis was carried out for categorical variables using the risk ratio (RR), LogRR, and its 95% CI. The methodological quality of each randomized controlled trial (RCTs) was assessed according to the Cochrane Collaboration tool to assess the risk of bias (ROB). A meta‐analysis of five studies with 228 participants was conducted. The risk ratio of patients whose MRS score was 0–1 at day 90 between fingolimod plus standardized treatment and standardized treatment alone was 2.59 (95%CI, 1.48–4.56). The Fingolimod plus standard treatment group decreased infarct growth and improved clinical function than the standard treatment.

The Efficacy and Safety of the Sphingosine-1-Phosphate Receptor Agonist Fingolimod in Cerebrovascular Stroke: A Systematic Review and Meta-analysis

“…The ndings in this study are consistent with the rst two meta-analyses on animal studies regarding the e cacy of ngolimod therapy started two days before stroke induction and continued for seven days in reducing infarct volume and improving functional outcomes in ischemic stroke models (24,41), and the only human meta-analysis by Bai et al investigating ischemic stroke patients after ngolimod initiation no later than 72 hours of symptoms onset and for three consecutive days (42). In contrast, this study is the rst to analyze hemorrhagic stroke patients, and in comparison with Bai's study ndings, we introduce several promotions.…”

Effects of cognitive training and behavior modification on aggressive behavior and sleep quality in schizophrenia

“…The following criteria were taken into account for study eligibility: (1) individuals aged between 18 and 60 years, (2) diagnosed with SCZ according to DSM-IV criteria or having schizoaffective disorder with an illness duration exceeding 5 years, (3) displaying a rating of five or higher on the aggression items of the Life History of Aggression scale or having committed a confirmed assault within the previous year, (4) obtaining a total score of 15 or higher on the Insomnia Severity Index (ISI), and (5) showing no signs of significant neuropathology or pre-existing intellectual disability based on the patient's family or guardian's understanding of the patient's previous state of life and social behavior.…”

“…The extent of disturbance SCZ causes in an individual's daily functioning varies significantly, ranging from high-level functionality in some cases to severe disability in others. In the United States, individuals with this condition face an average potential loss of 28.5 years of life (3)(4)(5)(6). Pharmacological and brain imaging studies have demonstrated that disruptions in dopamine neurotransmission can result in psychiatric symptoms, such as delusions and hallucinations, whereas aberrant glutamate signaling may contribute to negative and cognitive symptoms (7)(8)(9).…”

Thromboinflammatory challenges in stroke pathophysiology

“…Similarly, fingolimod, a sphingosine-1-phosphate (S1P)-receptor modulator used in the treatment of multiple sclerosis, has been tested in several clinical trials focusing on thromboinflammatory parameters. Recent data associates fingolimod administration with reduced infarct growth and improved neurological outcomes in clinical settings [ 13 , 229 ]. Despite still being in an early developmental stage, anti-inflammatory treatments for long-term stroke recovery may offer a promising therapeutic strategy and should therefore be seriously considered in future clinical routine (Table 1 ).…”

“…Novel therapeutic options within the thromboinflammatory field are currently emerging. Reduction in circulating lymphocytes using the immunosuppressant fingolimod is known to reduce infarct volume and improve neurological outcomes [ 13 , 229 ]. Additionally, early inhibition of GPVI (Glenzocimab) appears to be one of the most promising approaches currently under clinical evaluation aiming to modulate the thrombotic and pro-inflammatory pathways after the ischemic event.…”