Assessing the Incidence of Elevation in Eosinophils with the Use of Dimethyl Fumarate in Multiple Sclerosis

Background: Dimethyl fumarate (DMF) is an oral medication approved for the treatment of multiple sclerosis (MS). In the pivotal MS studies involving DMF, a transient increase in mean eosinophils were seen during the first 2 months of therapy. However, the incidence of this increase has not been reported.

Objectives: To assess incidence of elevation in eosinophils with the use of dimethyl fumarate in multiple sclerosis.

Methods: A retrospective chart review was conducted of all patients seen in our MS clinic from 3/2013 through 3/2014. The review focused on patients who were prescribed DMF under routine clinical care and available pre- and post-dosing complete blood counts (CBC), which included levels of eosinophils. Elevation in eosinophils in our chart review was defined as elevation above 7% of all leukocytes on differential. 

Results: A total of 191 patients started on DMF. A pre-dosing CBC was completed in 91.1% of patients and was obtained, on average, 10.9 weeks prior to starting DMF. A post-dosing CBC was completed in 77.5% of patients and was obtained, on average, 17.6 weeks after starting DMF. The incidence of elevation in eosinophils among patients who had post-dosing CBCs was 8.1%.

Conclusions: To our knowledge, this is the first study assessing incidence of elevations in eosinophils with the use of DMF in MS. There are several potential clinical implications for this data. First, it has been postulated that DMF-related gastrointestinal symptoms could be due to an eosinophilic gastroenteritis-like syndrome. Second, a transient increase in eosinophils has been observed with fumaric-acid esters, a similar compound to DMF used in psoriasis. This was attributed to elevations in IL-4 which stimulate eotaxin, an eosinophil-activating cytokine. DMF has also been shown to elevate IL-10, which along with IL-4 decreases Th1 cells and increases Th2 cells. Given that Th2 activation would be beneficial in MS, this increase in eosinophils might imply a positive treatment response and thus could be considered a biomarker. Further studies are indicated to investigate this.