Fumarate-induced lymphopenia in multiple sclerosis: A retrospective analysis
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Published on: February 28, 2021
Katherine E Selwa1, Lana E Sharba1, Preeta Gupta-Gardner1
1Department of Neurology and Multiple Sclerosis Center, University of Michigan, Ann Arbor, MI, USA.
Purpose:
Lymphopenia is an expected side effect of fumarate-based multiple sclerosis (MS) disease modifying therapies. Although ≤5% of participants in fumarate clinical trials experienced grade 2-3 lymphopenia, real-world observation suggests higher incidence (Gold et al., 2012, 2020). Beyond increased age, consensus regarding risk factors for lymphopenia is lacking.
Methods:
This retrospective chart review evaluated incidence and severity of lymphopenia among 274 patients treated with fumarates and examined associations between fumarate-associated lymphopenia and clinical variables with univariate and multivariate analyses.
Major Findings:
Ninety (32.8%) patients developed grade ≥2 lymphopenia while on treatment. Absolute lymphocyte count (ALC) dropped by an average of 46% (SD 0.27) from baseline. Older age upon fumarate initiation was significantly associated with grade ≥2 lymphopenia (1.048 (95% CI=1.023, 1.074), p=0.0001). Other variables significantly associated with grade ≥2 lymphopenia included co-administration of dalfampridine (3.283 (95% CI=1.347, 8.003), p=0.0089). These associations were maintained in multivariate analysis. Among those who developed grade ≥2 lymphopenia, ALC recovered to ≥1.0 K/mL in 61%, with average time of 22 months (SD 23) after treatment discontinuation.
Conclusions:
In this real-world clinical cohort, fumarate-associated lymphopenia incidence exceeds published estimates. Our findings support age as a risk factor and reveal unexpected associations between lymphopenia and co-use of dalfampridine that require further study.
