Female Gender, Natalizumab Exposure Associated With Increased Lymphopenia Risk in FNG-Treated MS

The impact of treatment with dimethyl fumarate and fingolimod on lymphocyte and leukocyte count was evaluated in patients with multiple sclerosis.

Exposure to natalizumab and female sex are associated with increased risk of lymphopenia in patients with multiple sclerosis (MS) taking fingolimod (FNG), according to findings published in Multiple Sclerosis and Related Disorders. An increased lymphopenia risk was also found in patients with low absolute lymphocyte count taking dimethyl fumarate (DMF).

Patients with MS taking DMF (n=405) were compared with patients with MS taking FNG (n=300) for ≥12 months. The study investigators obtained complete blood counts with differentials at baseline and at 6-month increments throughout treatment. In addition, the majority of participants had complete neurologic examinations and brain magnetic resonance imaging every 6 and 12 months, respectively. The investigators also obtained T cell subset profiles for 116 patients.

Female patients taking FNG had a significantly higher risk for developing lymphopenia grade 4 (<200) than males on the same medication (P =.0117). In addition, patients taking FNG were more likely to develop lymphopenia grade 4 if they had a treatment history of natalizumab (P =.0116). Female patients were also more likely to develop lymphopenia grade 3b+4 (<350) (P =.0009).

In the DMF-treated patients, higher odds of developing lymphopenia grade 2 (<800) or 2+3 (<500) was associated with having a lower lymphocyte count at baseline (P <.0001 for both). Treatment switch between DMF and FNG did not result in any significant recovery of leukocyte or lymphocyte count.

While the reduction of FNG dosing in patients with lymphopenia resulted in an increased lymphocyte count, it tended to increase disease activity in approximately 25% of the patients.

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The retrospective design of this study represents a potential limitation to the findings. In addition, the small number of patients with an available lymphocyte count at baseline limited the ability to draw conclusive associations.

While significant differences were found in lymphocyte profiles between patients with MS with and without lymphopenia, additional study may be warranted to generate evidence-based guidelines for predicting lymphopenia in these patients.


Baharnoori M, Gonzalez CT, Chua A, et al. Predictors of hematological abnormalities in multiple sclerosis patients treated with fingolimod and dimethyl fumarate and impact of treatment switch on lymphocyte and leukocyte count. Mult Scler Relat Disord. 2017;20:51-57.