Gilenya-induced Changes in Heart Rate May Predict Degree of Drop in Lymphocytes, Study Reports

Assessing changes in a person’s heart rate can help to predict the degree to which lymphocyte numbers will decrease in relapsing-remitting multiple sclerosis (RRMS) patients using Gilenya (fingolimod), according to a small study.

The research, “Fingolimod-induced decrease in heart rate may predict subsequent decreasing degree of lymphocytes,” was published in the journal Scientific Reports.

Lymphopenia, or an abnormally low level of lymphocytes (a type of white blood cell) in the blood, results from Gilenya’s binding to S1P1 receptors on lymphocytes, retaining these cells in lymph nodes. Although this is the intended effect of the therapy, in excess it can raise a person’s risk of infection. As such, having a marker to predict an excessive lowering in lymphocyte numbers after treatment with Gilenya would be beneficial.

Activating the S1P1 receptor on cardiomyocytes, the cells that make up the cardiac muscle, is also known to slow the heart rate. Assuming that the mechanism driving a lower heart rate and lymphopenia is similar, researchers in Japan evaluated whether the degree of a Gilenya-induced reduction in heart rate correlates with a later decrease in lymphocyte counts in RRMS patients.

Their study included 30 people taking 0.5 mg Gilenya orally (marketed by Novartis), whose heart rate was recorded every 30 minutes for 24 hours. Adjusting for age and sex, the scientists estimated heart rate curves for each patient. Two components, called amplitude — a measure of change — and phase angle — the degree of the change measured, were analyzed for individual curves. The team also assessed pre-and post-treatment differences in the levels of leukocytes (white blood cells) and their subtypes: lymphocytes, monocytes, and neutrophils.

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Results showed strong correlations between changes in leukocytes and lymphocytes or neutrophils levels. A moderate correlation was found between differences in leukocyte and monocyte counts.

The curves’ amplitude correlated with lymphocyte numbers, and to a lesser extent with leukocyte and monocyte counts, but not with neutrophils. Then, supporting the known link between being underweight and low lymphocyte levels in women, the investigators found that body weight correlated with levels of these cells in women, but not in men.

Exploring different lymphocyte numbers in patients with distinct heart rate responsiveness, researchers also saw a greater decrease in lymphocyte numbers in individuals with high heart rate amplitude (reflecting a more pronounced effect of Gilenya) than in those with low amplitude. As previously reported, pre-Gilenya lymphocyte numbers correlated with a treatment-induced decrease in lymphocyte numbers.

Data “suggest that the degree of decreased lymphocytes after fingolimod treatment (main effect) may be predicted by estimating the influence of degree in heart rate (side effect),” the scientists wrote.

“By monitoring heart rate for 24 hours after fingolimod [Gilenya] treatment, neurologists may be able to use [heart rate] amplitude information to detect an excessive influence of fingolimod” on lymphocyte counts and their likely decrease, the researchers added.

As such, they suggested that earlier follow-up visits be considered to check lymphocyte counts in RRMS patients using Gilenya.