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)