Safety and persistence of dimethyl fumarate as a treatment for relapsing-remitting multiple-sclerosis

Dimethyl fumarate is a medication approved for the treatment of relapsing-remitting multiple sclerosis. The purpose of the  study was to evaluate the safety and persistence of dimethyl fumarate in  clinical practice and analyze the occurrence of lymphopenia is patients  treated with dimethyl fumarate over a period of at least 6 months.

This is a retrospective longitudinal observational study carried out between August 2015 and March 2019. The study cohort was  made up of patients who had been treated with dimethyl fumarate for at  least 6 months. Lymphocyte counts were recorded at different points of  time (pre-treatment, at 3, 6, 12 months, and at the end of the study  period). The evolution of lymphopenia was evaluated by means of a  logistic regression statistical model. An analysis was performed of the  relationship between a decreased lymphocyte count over the first 6  months of treatment and the development, by the end of the study, of  grade II-III lymphopenia necessitating discontinuation of dimethyl  fumarate. Other safety indicators were also evaluated including adverse  events and interruptions or discontinuations of treatment. Persistence was  determined by measuring the time to discontinuation of treatment.

The study included a total of 55 patients, of whom 80% were female. The most common adverse events were lymphopenia (27),  rubefaction (16), digestive symptoms (11), fatigue (9), headache (3) and  sleep disturbances (2). Eleven subjects interrupted/discontinued their  treatment during the study period; reasons were as follows: pregnancy  (2), personal decision (2), John Cunningham virus infection (1), allergy to  the drug (2), and lymphopenia (4). Median duration of treatment was 23  months (4-43 months). A statistically significant association was found  between a lower lymphocyte count over the first 6 months of treatment  and the development of severe lymphopenia by the end of the study [OR  = 1.34 (0.35-2.60); 95% CI (p = 0.001)].

The adverse events observed in the present study are in line with those reported in previous analyses. Lymphopenia was the  most common adverse event. The persistence of the medication was  similar to that found in pivotal trials. The significant association found  between a decreased lymphocyte count over the first 6 months of  treatment and the development of severe lymphopenia by the end of the  study suggests a connection between both variables, which could be  instrumental in being able to predict and even prevent the occurrence of  such lymphopenias.