Lymphocyte Counts after Initiation of Dimethyl Fumerate

Background: Dimethyl fumerate (DMF) is a first line oral therapy for relapsing remitting multiple sclerosis (RRMS) but prolonged lymphopenia may jeopardise safety.

Objectives: This retrospective cohort study aims to determine lymphocyte count change after initiation of DMF in a real world clinical setting.

Methods: Data from patients with RRMS who initiated DMF between July 1, 2013 and December 31, 2014 were analyzed. The Calgary MS Clinic has managed over 2,500 disease modifying therapy (DMT) patients; administrative processes, electronic medical record (EMR) and a database assure that use is tracked. A checklist is used to support patient education and safety prior to starting DMT. Demographic, clinical and lab information were collected from patient EMRs and the clinic database.

Results: This analysis included 170 patients. At treatment initiation mean age was 42.1 years, 75% were women, mean disease duration was 12.5 years, median EDSS was 2, and 24% were treatment naïve. Median follow-up time to December 31, 2014 was 6.4 months (range: 1.5-17.7). DMF was discontinued by 17 patients (10%); median time to discontinuation was 3.1 months (range: 0.6-12.4). Mean lymphocyte count at baseline was 2.0 x 10⁹ cells/L (range: 0.5-4.4). Among 84 (49%) patients followed for 6 months, only 61 (73%) had a 6-month blood test for safety monitoring, mean lymphocyte count was 1.4 x 10⁹ cells/L (range: 0.4-2.6). Lymphocyte counts decreased in 55 (90%) patients from baseline to 6 months with a mean absolute change of -0.72 x 10⁹ cells/L (range: -2.8 to +0.8) and a mean percent change of -32% (range: -74% to +50%).  Lymphopenia (lymphocyte count < 0.5) occurred at least once during follow-up in 5 patients (3%); this was the most recent lab test in some patients and in other patients it was transient. No patient discontinued DMF as of December 31, 2014 due to lymphopenia.

Conclusions: The Canadian product monograph for DMF indicates that the lymphocyte count will decrease by 30% within the first year and lymphopenia will occur in < 6%; these data are consistent with this expectation. However, improved patient adherence to lab monitoring is needed as lymphopenia is very likely to be missed when such a large proportion of patients (27% at this time point) fail to comply with safety monitoring. Adherence to lymphocyte monitoring, and lymphocyte results, over the first year of treatment will be presented.