Meta-Analysis
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Meta-Anal. Dec 28, 2021; 9(6): 585-597
Published online Dec 28, 2021. doi: 10.13105/wjma.v9.i6.585
Efficacy and safety of fingolimod in stroke: A systemic review and meta-analysis
Kai Zhao, Yu Guo, Ming-Fei Yang, Qiang Zhang
Kai Zhao, Yu Guo, Graduate School, Qinghai University, Xining 810016, Qinghai Province, China
Ming-Fei Yang, Qiang Zhang, Department of Neurosurgery, Qinghai Provincial People's Hospital, Xining 810007, Qinghai Province, China
Author contributions: Zhang Q and Zhao K conceived the idea and designed the study; Zhao K and Guo Y screened the studies and extracted the data independently; Yang MF and Guo Y analysed and interpreted the data; Zhao K and Guo Y wrote the first draft of the manuscript; Zhang Q proofread the manuscript before submission; all authors reviewed the manuscript and approved the final version.
Supported by the National Key R&D Program of China, No. 2018YFC1312601; and the Project of Science and Technology Department of Qinghai Province, No. 2020-ZJ-774.
Conflict-of-interest statement: On behalf of all authors, the corresponding author states that there is no conflict of interest to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qiang Zhang, MD, PhD, Chief Doctor, Surgeon, Department of Neurosurgery, Qinghai Provincial People's Hospital, No. 2 Gonghe Road, Xining 810007, Qinghai Province, China. zhangqiang691212@163.com
Received: August 18, 2021
Peer-review started: August 18, 2021
First decision: November 2, 2021
Revised: November 13, 2021
Accepted: December 24, 2021
Article in press: December 24, 2021
Published online: December 28, 2021
Processing time: 132 Days and 4.6 Hours
Abstract
BACKGROUND

Brain tissue injury in stroke patients involves inflammation around the infarction lesion or hematoma, which is an important reason for disease deterioration and can result in a poor prognosis. The meta-analysis of animal experiments has concluded that fingolimod could treat stroke in animal models by effectively reducing lymphocyte infiltration. However, no evidence-based efficacy and safety evaluation of fingolimod in stroke patients is currently available.

AIM

To determine whether fingolimod could promote reduction of infarction lesion or hematoma and improve neurological prognosis in stroke patients.

METHODS

Data extracted for treatment effect included count of T-lymphocytes with cluster of differentiation 8 expression (CD8+ T cells, × 106/mL), lesion volume (infarction or hematoma, mL), and modified Barthel indexes. Data extracted for safety was risk ratio (RR). Overall standard mean difference (SMD) with its 95% confidence interval (95%CI) and pooled effect with its 95%CI were calculated with a fixed-effects model. I-square (I2) was used to test the heterogeneity. Funnel plot symmetry and Egger's regression were used to evaluate publication bias.

RESULTS

Four high-quality randomized controlled trials were included. There was a significant difference in CD8+ T cell count (I2 = 0, overall SMD = -3.59, 95%CI: -4.37-2.80, P = 0.737) and modified Barthel index (I2 = 0, overall SMD = 2.42, 95%CI: 1.63-3.21, P = 0.290) between the fingolimod and control groups. However, there was no significant difference in lesion volume (I2 = 10.6%, overall SMD = -0.17, 95%CI: -0.75-0.42, P = 0.917), fever (pooled RR = 0.93, 95%CI: 0.97-2.32, P = 0.864), suspected lung infection (pooled RR = 0.90, 95%CI: 0.33-2.43, P = 0.876), or any adverse events occurring at least once (pooled RR = 0.82, 95%CI: 0.36-1.87, P = 0.995) between the fingolimod and control groups. There was no publication bias. All of the results were stable as revealed by sensitivity analysis.

CONCLUSION

Fingolimod improves neurological function in stroke patients without promotion of lesion absorption. Taking fingolimod orally (0.5 mg/d, 3 consecutive days) is safe except for patients with rare severe adverse events.

Keywords: Acute ischemic stroke; Intracerebral hemorrhage; Fingolimod; Meta-analysis; Treatment

Core Tip: Brain tissue injury in stroke patients involves inflammation around the infarction lesion or hematoma, which is an important reason for disease deterioration and can result in a poor prognosis. Our systemic review and meta-analysis of recent randomized controlled trials found that fingolimod might improve neurological function in stroke patients by reducing lymphocyte infiltration in the brain effectively; however, we did not find the evidence that fingolimod could promote infarction lesion or hematoma absorption. In general, oral fingolimod (0.5 mg/d, 3 consecutive days) was safe in stroke patients except for some rare severe adverse events.