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. 2020 Apr 29;6(2):2055217320918619.
doi: 10.1177/2055217320918619. eCollection 2020 Apr-Jun.

Effect of dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis

Guy Buckle  1 , Daniel Bandari  2 , Jeffrey Greenstein  3 , Mark Gudesblatt  4 , Bhupendra Khatri  5 , Mariko Kita  6 , Pavle Repovic  7 , Emily Riser  8 , Bianca Weinstock-Guttman  9 , Ben Thrower, Sherrill Loring  1 , Katherine Riester  10 , Nick Everage  10 , Claudia Prada  10 , Irene Koulinska  10 , Monica Mann  10
Affiliations

Effect of dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis

Guy Buckle et al. Mult Scler J Exp Transl Clin. .

Abstract

Background: In patients treated with dimethyl fumarate, absolute lymphocyte count decline typically occurs during the first year and then plateaus; early drops have been associated with the development of severe prolonged lymphopenia.

Objective: We investigated the effect of dimethyl fumarate on absolute lymphocyte counts and CD4+/CD8+ T cells in patients with relapsing-remitting multiple sclerosis treated with dimethyl fumarate in routine practice.

Methods: Lymphocyte data were collected via medical chart abstraction. Primary endpoint: change from baseline in absolute lymphocyte count and CD4+/CD8+ counts at 6-month intervals following dimethyl fumarate initiation.

Results: Charts of 483 patients were abstracted and 476 patients included in the analysis. Mean baseline absolute lymphocyte count (2.23 × 109/l) decreased by ∼39% (95% confidence interval: -41.1 to -37.2) by month 6 and 44% (95% confidence interval: -46.6 to -42.1) by month 12. CD4+ and CD8+ T-cell subsets strongly correlated with absolute lymphocyte count, with greater decreases from baseline to 6 months vs 6-12 months, and in CD8+ vs CD4+ T cells. Prior natalizumab was not a risk factor for lymphopenia.

Conclusion: Dimethyl fumarate-associated decline in absolute lymphocyte count in the first 12 months correlated with decline in CD4+ and CD8+ T cells and was independent of prior natalizumab. Absolute lymphocyte count monitoring continues to be an effective strategy to identify patients at risk of prolonged lymphopenia.

Keywords: Multiple sclerosis; T-cell subsets; absolute lymphocyte count; dimethyl fumarate; natalizumab.

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Figures

Figure 1.
Figure 1.
Observed (a) absolute lymphocyte count (ALC), (b) CD4+ count, and (c) CD8+ count over time. Change from baseline ALC was estimated using repeated-measures mixed-effects model analysis.
Figure 2.
Figure 2.
Individual absolute lymphocyte count (ALC) values before and after delayed dimethyl fumarate (DMF) discontinuation and regression line. The regression line was calculated by locally estimated scatterplot smoothing with linear interpolation.
See this image and copyright information in PMC

References

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