Evaluating Effect of Dimethyl Fumarate on Leukocytes Among Caucasian-, African- and Hispanic-American Patients with Multiple Sclerosis (MS)

Background: Dimethyl fumarate (DMF) demonstrated significant efficacy in two randomized clinical trials for treatment of relapsing remitting multiple sclerosis (RRMS). However, trials included few patients of African-American (AA) and Hispanic backgrounds. Recent reports of Progressive Multifocal Leukoencephalopathy (PML) in patients treated with DMF, possibly related to leukopenia developing after the start of the drug, is of concern. Identifying cohorts of patients at increased risk of leukopenia related to DMF is imperative to potentially reduce risk in clinical practice.    

Objectives: To evaluate DMF effect on leukocytes in patients with MS across different ethnic groups at two MS Centers, which serve ethnically diverse patient populations.   

Methods: Retrospective chart review was performed of all clinic patients who were started on DMF in the first year of drug availability. Ethnicity was derived from patient self-description. Relapses and new T2 and Gad-enhancing lesions were recorded 1 year prior to and while on DMF therapy. White blood cell counts (WBC) recorded prior to start of DMF and throughout treatment will be captured. In addition, John Cunningham Virus antibody (JCVab) index value and treatment prior to DMF will be recorded. Results of multivariate analyses will be presented.

Results:  Initial analysis of date revealed: 422 MS patients were started on DMF. Average age was 45 years (range 21 – 79); 74% were women. Ethnicity was available for 85% of patients, which was comprised of 56% Caucasians; 17% AA; 12% Hispanic.  Mean duration of MS symptoms was 6 years (range 1-55). Mean duration of treatment was 8 months, (range 0-16). 12% of patients were drug naïve. DMF was discontinued by 17% of patients, most frequently due to GI side effects, 5%.  Reduction in annual relapse rate (ARR) was seen across all ethnic groups when compared to ARR one year prior to start of DMF (Caucasians 0.31 to 0.11; AA 0.28 to 0.04; Hispanic 0.18 to 0.12). Similar reduction in new T2 lesion rate was seen across all groups: Caucasian 59%; AA and Hispanics 56%. Gadolinium enhancing lesions were reduced by 63% in Caucasian and Hispanic cohort, 64% in AA. Discontinuation rate was 29% with 5% related to leukopenia (Caucasian 2%, AA 0%, Hispanic 2%). Ongoing analysis includes: WBC prior to DMF and throughout treatment; JCvab status; treatment prior to DMF start.

Conclusions: Current study demonstrates DMF efficacy and tolerability appears to be similar across three main ethnic groups. Clinically significant DMF related leukopenia appears to be a relatively rare event among the Caucasian, AA, and Hispanic population seen in our practice.  DMF effect on leukocytes will continue to be monitored in this cohort.