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Infection Risk May Increase With Fingolimod Use in Patients With MS


Among patients with multiple sclerosis, there is a 16% greater risk of infection, including for lower respiratory and herpes virus infections, after administration of fingolimod.

A 16% greater risk of infection was seen following administration of fingolimod among patients with multiple sclerosis, (MS) including that for lower respiratory and herpes virus infections, according to results recently published in Frontiers in Immunology.

Fingolimod is a second-generation disease-modifying therapy (DMT), and the first oral one, approved by the FDA in 2010.

To have a better understanding of the risk stemming from fingolimod use, the authors searched PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov from inception through April 8, 2020. Search terms included "Multiple sclerosis"; "Sclerosis, Multiple"; "related-limiting Multiple Sclerosis"; "fingolimod"; "Gilenya"; and "clinical trial."

“There is a controversy regarding whether fingolimod is associated with an increased risk of infection in patients with multiple sclerosis,” the authors explained, clarifying that safety concerns were raised in several previous trials.

All randomized controlled trials included in their final analysis (N = 12 trials and 8448 patients) had to have data on participants’ infection rate. Among the included patients, 62.2% were treated with fingolimod and 37.8% with a placebo or a first-generation DMT.

This analysis revealed a uniform higher risk of infection with fingolimod across several general classifications:

  • There was an overall 16% greater risk of infection with fingolimod (relative risk [RR], 1.16; 95% CI 1.07-1.27; I2, 81%)
  • The risk of general infection was 14% elevated (RR, 1.14; 95% CI, 1.05-1.25; I2, 78%)
  • There was a 49% higher risk of serious infection (RR, 1.49; 95% CI, 1.06-2.10; I2, 0%)

When drilling down to specific viruses, higher risks were especially apparent for lower respiratory infections and herpes virus infections:

  • Lower respiratory infections had a 48% greater chance of happening following fingolimod use (RR, 1.48; 95% CI, 1.19-1.85; I2, 0%)
  • Herpes virus infections had a 34% greater chance of happening following fingolimod use (RR, 1.34; 95% CI, 1.01-1.78, I2, 9%

No significant risk differential was seen among the following infections:

  • Upper respiratory tract (RR, 1.05; 95% CI, 0.87-1.27; I2, 86%)
  • Influenza virus (RR, 1.09; 95% CI, 0.90-1.33; I2, 1%)
  • Digestive system (RR, 0.95; 95% CI, 0.65-1.39; I2, 0%)
  • Urinary system (RR, 1.05; 95% CI, 0.84-1.33; I2, 48%)
  • Abscess (RR, 1.32; 95% CI, 0.45-3.91; I2, 0%)

Importantly, the link with risk is likely not related to dose of the sphingosine l-phosphate receptor modulator: a 0.5-mg dose (n = 6660) had a 15% greater risk of infection (RR, 1.15; 95% CI, 1.07-1.25; I2, 91%) compared with 11% seen with a 1.25-mg dose (n = 2521) (RR, 1.11; 95% CI, 0.97-1.28; I2, 81%; Pinteraction = .66).

Overall, the pooled participants demonstrated a 56.8% infection rate when treated with fingolimod compared with 52.2% seen in the controls.

Infection risk is one of several principal concerns for clinicians when they are prescribing DMTs for patients with MS, the authors note, proposing 2 potential reasons for the higher fingolimod-associated risk they saw:

  1. Fingolimod causes internalization of S1P1R from the cell membrane in lymph node T cells, which can ultimately lead to fewer T cells migrating to the central nervous system
  2. Fingolimod impedes T cells from producing fewer cytokines that help to kill congenital effector cells and promote T-cell differentiation

“Summarily, understanding the infectious effects of fingolimod taking into account the prevention, is preferable to treatment,” they concluded.


Zhao Z, Ma C-L, Gu Z-C, Dong Y, Lv Y, Zhong M-K. 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. Front Immunol. Published online March 8, 2021. doi:10.3389/fimmu.2021.611711

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