Predictors of hematological abnormalities in multiple sclerosis patients treated with fingolimod and dimethyl fumarate and impact of treatment switch on lymphocyte and leukocyte count

There is limited data regarding the predictors of hematological abnormalities in multiple sclerosis (MS) patients treated with dimethyl fumarate (DMF) or fingolimod (FNG), and the impact of treatment switch on lymphocyte and leukocyte count We identified 405 patients on DMF and 300 patients on FNG (...

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Bibliographic Details
Published in:Multiple sclerosis and related disorders 2018-02, Vol.20, p.51-57
Main Authors: Baharnoori, M., Gonzalez, C.T., Chua, A., Diaz-Cruz, C., Healy, B.C., Stankiewicz, J., Weiner, H.L., Chitnis, T.
Format: Article
Language:English
Subjects:
Dimethyl fumarate
FNG
Lymphopenia
Multiple sclerosis
Risk mitigation
Treatment switch
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Summary:There is limited data regarding the predictors of hematological abnormalities in multiple sclerosis (MS) patients treated with dimethyl fumarate (DMF) or fingolimod (FNG), and the impact of treatment switch on lymphocyte and leukocyte count We identified 405 patients on DMF and 300 patients on FNG (treatment duration: at least 12 month) within a large prospective study of MS patients conducted at the Partners MS Center, Brigham and Women's Hospital (CLIMB study) between Jan 2011 to Feb 2016. Patients had complete blood counts with differentials at baseline and every 6 months while on treatment. Most participants had a clinical visit with complete neurologic examinations every 6 months and brain MRI scan every 12 months. T cell subset profile was available for subgroup of patients (n = 116). In the FNG group, the risk of developing lymphopenia grade 4 (< 200) was higher in female patients (p = 0.0117) and those who were previously treated with natalizumab (p = 0.0116), while the risk of lymphopenia grade 3b+4 (< 350) was higher in female patients (p = 0.0009). DMF treated patients with lower baseline lymphocyte count had a higher chance of developing lymphopenia grade 2 (< 800) (p < 0.0001) or 2+3 (< 500) (p < 0.0001). We examined the effect of treatment switch between DMF and FNG. No significant recovery in lymphocyte and leukocyte count was observed after treatment switches. Reduced dosing of FNG in patients with lymphopenia led to increase in lymphocyte count but also increased disease activity in 25% of patients. Female sex and prior exposure to natalizumab increased the probability of lymphopenia on FNG, while low absolute lymphocyte count was associated with increased risk of lymphopenia on DMF. Parallel switch did not lead to recovery from hematological abnormalities. Long-term studies with larger number of patients are required to confirm our findings and to establish guidelines for prediction and management of hematological abnormalities. •Lymphocyte subset profiles in lymphopenic and non lymphopenic patients on dimethyl fumarate (DMF) and fingolimod were studied.•Female sex and prior exposure to natalizumab increased the probability of lymphopenia on fingolimod.•Older age was associated with increased risk of lymphopenia in patients treated with DMF.•Parallel switch did not lead to recovery from hematological abnormalities.•Reduced dose regimen of fingolimod led to modest increase in lymphocyte count but increased disease activity.
ISSN:2211-0348
2211-0356
DOI:10.1016/j.msard.2017.12.003