Gilenya Increases Patient Infection Risk, Clinical Data Suggest

The multiple sclerosis (MS) treatment Gilenya (fingolimod) is associated with a 16% greater risk of infections, compared with a placebo or control treatment, according to data from 12 randomized clinical trials.

The findings were published in a study, “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,” in the journal Frontiers in Immunology.

Gilenya is an oral treatment from Novartis that’s approved for relapsing forms of MS in people ages 10 and older. It works by retaining immune cells in lymph nodes (immune-related structures) and preventing them from reaching the brain and spinal cord, where they could cause damage to the protective myelin sheath surrounding nerve fibers.

By reducing the number of immune cells in circulation, Gilenya may reduce the immune system’s ability to fight off infectious pathogens. Yet, whether Gilenya treatment is associated with a greater risk of infections compared with other MS treatments remains controversial.

To shed light on this, researchers in China reviewed data from published clinical trials that assessed Gilenya, against a placebo or other disease-modifying therapies (DMTs), in MS patients.

The team conducted a literature search in different databases — including PubMed, EMBASE, the Cochrane Library, and the clinicaltrials.gov website — for controlled clinical trials that assessed infections in MS patients given Gilenya.

From an initial pool of 2,659 records, a total of 12 clinical trials were included in the final analysis. These 12 studies were published from 2010 to 2019, had durations ranging from six weeks to two years, and included a total population of 8,448 patients.

Overall, 62.2% of patients had been assigned randomly to Gilenya and 37.8% received a placebo or first-generation DMT — interferon-beta, glatiramer acetate, or Tysabri (natalizumab).

In all 12 studies, Gilenya was administered at a low dose (0.5 mg daily), but four also investigated a high treatment dose (1.25 mg daily).

The analysis revealed that the overall risk of infection was 16% higher among patients treated with Gilenya than in control patients. That risk was 14% greater for a general infection, but increased to 49% for serious infections.

Looking at different types of infections, the analyses further showed that, compared to control groups, Gilenya significantly increased the risk of lower respiratory infections by 48% and of infection by the herpes virus by 34%.

Other infections affecting the upper airways, and the digestive and urinary systems, abscesses, and infections caused by the influenza virus were not significantly different among Gilenya and control patients.

Also, the risk of infection associated with Gilenya might not be dose-related, as low and high doses were associated with similar risks (15% and 11%).

Overall, Gilenya “significantly increased the risk of infection, especially lower respiratory infection and herpes virus infections, in patients with MS,” the researchers wrote.

They suggested that the mechanism of action of Gilenya, the trapping of lymphocytes, as well as its more general impact on the immune system are likely factors underlying the increased risk of infection.

However, additional studies are needed to clarify if Gilenya is also associated with an increased risk of infection in the real-world setting, the team added.