Dimethyl fumarate (DMF) is an oral therapy approved for patients with relapsing-remitting multiple sclerosis (RRMS), and in which lymphocyte decline is a known pharmacodynamic effect of DMF. Currently, research has suggested meaningful lymphocyte reconstitution may occur within 2-4 months after discontinuation of DMF. To date, the only factor shown to be associated with a slower rate of recovery is the duration of lymphopenia.
To describe lymphocyte count profiles following discontinuation of Dimethyl fumarate (DMF) due to lymphopenia in a nationwide Swedish population-based setting.
The IMSE-5 study obtains demographics, clinical and safety data, including absolute lymphocyte count (ALC), from the Swedish population-based Neuro Registry. Key inclusion criteria were RRMS patients, treatment with DMF for at least 3 months, age >18 years at initiation, had ALC values at start of DMF treatment, during treatment, and following discontinuation of DMF treatment. All patients had discontinued DMF due to lymphopenia. The least square mean estimation of ALC values at different time points was calculated using Linear Mixed Models
A total of 18 DMF patients were included, 72% were female and the mean age at treatment start was 51.3 years. The mean treatment duration was 3.1 (SD 0.8) years, and 22% were treatment naïve, 50% had switched from interferons or glatiramer acetate (GA). and three patients switched from natalizumab and fingolimod. The estimated ALC values following discontinuation of DMF due to lymphopenia compared to the time for discontinuation significantly increased during follow up (p<0.001). E.g. at date of drug discontinuation mean ALC was 0.35x109/L (95% CI 0.33-0.37), in 6 weeks following discontinuation ALC was 0.50 x109/L (95% CI 0.26-0.74) and in 12 weeks ALC increased to 0.91 x109/L (95% CI 0.74-1.07). The mean time from discontinuation to a new treatment initiation following DMF was 99.8 (SD 88.5) days; and 50% switched to rituximab and two patients to teriflunomide, and one to GA.
Data from the Swedish IMSE-5 study suggest that a lymphocyte reconstitution occurs within 12 weeks following the discontinuation of DMF. However, larger datasets will be needed to verify this finding
Funding: The IMSE-5 study is funded in a scientific collaboration agreement with Biogen.