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Meta-Analysis
. 2021 Mar 8:12:611711.
doi: 10.3389/fimmu.2021.611711. eCollection 2021.

Incidence and Risk of Infection Associated With Fingolimod in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis of 8,448 Patients From 12 Randomized Controlled Trials

Zhao Zhao  1 , Chun-Lai Ma  1 , Zhi-Chun Gu  2 , Yue Dong  1 , Yang Lv  1   3 , Ming-Kang Zhong  1
Affiliations
Meta-Analysis

Incidence and Risk of Infection Associated With Fingolimod in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis of 8,448 Patients From 12 Randomized Controlled Trials

Zhao Zhao et al. Front Immunol. .

Abstract

Background and Aims: There is a controversy regarding whether fingolimod is associated with an increased risk of infection in patients with multiple sclerosis (MS). We performed a systematic review and meta-analysis of data from randomized controlled trials (RCTs) to determine the risk of infection in these patients. Methods: We systematically searched PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov from inception to April 8, 2020, to identify RCTs that reported the occurrence of infection in patients with MS treated with fingolimod. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using the random-effects model. Results: Twelve RCTs including 8,448 patients were eligible. Compared with the control (placebo and other active treatments), fingolimod significantly increased the risk of infection (RR, 1.16; 95% CI, 1.07-1.27; I2, 81%), regardless of whether the infection was a general infection (RR, 1.14; 95% CI, 1.05-1.25; I2, 78%), or a serious infection (RR, 1.49; 95% CI, 1.06-2.10; I2, 0%). Analyses of subgroups found that fingolimod significantly increased the risk of lower respiratory infection (RR, 1.48; 95% CI, 1.19-1.85; I2, 0%) and herpes virus infection (RR, 1.34; 95% CI, 1.01-1.78; I2, 9%). There appears to be no dose-dependent increase in the risk of infection associated with fingolimod (0.5 mg: RR, 1.15; 95% CI, 1.07-1.25; I2, 91%; 1.25 mg: RR, 1.11; 95% CI, 0.97-1.28; I2, 81%; Pinteraction = 0.66). Conclusions: Compared with a placebo and other active treatments, fingolimod was associated with a 16% increase in the risk of infection, especially lower respiratory infection and herpes virus infection. The risk of infection associated with fingolimod might not be dose related.

Keywords: dose-dependence; fingolimod; infection; meta-analysis; multiple sclerosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram for the selection of eligible randomized controlled trials. RCTs, randomized controlled trials.
Figure 2
Figure 2
Forest plot with meta-analysis of the overall risk of infection. RR, relative risk; 95% CI, 95% confidence interval.
Figure 3
Figure 3
Forest plot with subgroup analysis of different types of infection. RR, relative risk; 95% CI, 95% confidence interval.
Figure 4
Figure 4
Forest plot with subgroup analysis of different doses of fingolimod for infection risk. RR, relative risk; 95% CI, 95% confidence interval.
See this image and copyright information in PMC

References

    1. Krieger SC. New approaches to the diagnosis, clinical course, and goals of therapy in multiple sclerosis and related disorders. Continuum. (2016) 22:723–9. 10.1212/CON.0000000000000324 - DOI - PubMed
    1. Reich DS, Lucchinetti CF, Calabresi PA. Multiple sclerosis. N Engl J Med. (2018) 378:169–80. 10.1056/NEJMra1401483 - DOI - PMC - PubMed
    1. Faissner S, Gold R. Progressive multiple sclerosis: latest therapeutic developments and future directions. Ther Adv Neurol Disord. (2019) 12:175628641987832. 10.1177/1756286419878323 - DOI - PMC - PubMed
    1. Grebenciucova E, Pruitt A. Infections in patients receiving multiple sclerosis disease-modifying therapies. Curr Neurol Neurosci. (2017) 17:88. 10.1007/s11910-017-0800-8 - DOI - PubMed
    1. Chun J, Hartung H. Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis. Clin Neuropharmacol. (2010) 33:91–101. 10.1097/WNF.0b013e3181cbf825 - DOI - PMC - PubMed

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