4.Discussion
This meta-analysis included 5 trials to assess the efficacy and safety of fingolimod in patients with AIS. Recently, the effectiveness and safety of fingolimod in patients with AIS have been investigated in some RCTs.(1, 2, 11, 18, 26). This systematic review and meta-analysis provide data to support the efficacy and safety of fingolimod for AIS.
Theefficacy of Fingolimod
Our meta-analysis presented that fingolimod resulted in more ischemic penumbra rescue and improved clinical function. Our primary endpoint here is based on a proportion of patients with MRS 0–1 at 90 days, decrease in NIHSS score at 24 hours, decrease in NIHSS score at day 7, decrease in NIHSS score at 90 days, relative infarct lesion growth at 24 hours, and relative infarct lesion growth at 7 days. The sensitivity analysis with analyses of the decrease in NIHSS score at 24 hours and at day 7 showed that the study by De-Cai Tian et al. 2017 significantly affected heterogeneity. It showed no statistically significant differences between fingolimod and standardized treatment in NIHSS score at day 7.
Studies have shown critical linkages between various immunomodulatory mechanisms in ischemic stroke.(18, 27) Ischemic stroke involves neuronal dysfunction and complex interactions between other cells, including vascular endothelial cells, BBB, extracellular matrix, and immune system.(28-30) Early clinical observations suggest a link between inflammation and ischemic stroke. Inflammation predisposes people to ischemic stroke and directly leads to many pathological changes.(29, 31-34) Further understanding of the relationship between immunity and brain tissue in ischemic stroke is helpful to develop new immunomodulatory therapy.
Fingolimod significantly reduced infarct expansion at 24h. Fingolimod not only inhibits lymphocyte infiltration into the brain parenchyma and protects brain tissue from secondary injury but also, at an earlier stage, by reducing the number of cells accumulating in the brain microvasculature. Inhibit the formation of capillary-inflammatory thrombosis and protect the function of the CNS.(35-38)In addition, fingolimod also targets intrinsic cells of the CNS, including vascular endothelial cells. It produces non-immune effects, thereby protecting brain tissue to some extent. The effect of fingolimod on vascular endothelial cells can inhibit the proinflammatory and thrombotic states of endothelial cells and improve the integrity of BBB.(35, 39)