Background Fumaric acid esters ( FAE s) are used to treat psoriasis and are known to cause lymphopenia in roughly 60% of the patients. Much remains to be elucidated about the biological effects of FAE s on lymphocytes. Objective To evaluate the influence of long‐term FAE (Fumaderm ® ) treatment on peripheral blood CD 4 + and CD 8 + T cells, CD 19 + B cells and CD 56 + natural killer ( NK ) cells in psoriasis. Methods In this single‐centre retrospective observational subcohort study, we obtained leucocyte and lymphocyte subset counts before initiating FAE therapy in 371 psoriasis patients (mean age, 47.8 years; 63.3% males) and monitored them during treatment (mean treatment duration, 2.9 years). Multiparametric flow cytometry was used for immunophenotyping. Results FAE s significantly reduced the numbers of CD 4 + T, CD 8 + T, CD 19 + B and CD 56 + NK cells. Among lymphocyte subsets, the mean percentage reduction from baseline was always highest for CD 8 + T cells, with a peak of 55.7% after 2 years of therapy. The risk of T‐cell lymphopenia increased significantly with the age of the psoriasis patients at the time that FAE therapy was initiated. It was significantly decreased for the combination therapy with methotrexate and folic acid (vitamin B9) supplementation. Supporting evidence was found suggesting that T‐cell lymphopenia enhances the effectiveness of FAE therapy. Conclusions Monitoring distinct T‐cell subsets rather than just absolute lymphocyte counts may provide more meaningful insights into both the FAE treatment safety and efficacy. We therefore suggest optimizing pharmacovigilance by additionally monitoring CD 4 + and CD 8 + T‐cell counts at regular intervals, especially in patients of middle to older age. Thus, further prospective studies are needed to establish evidence‐based recommendations to guide dermatologists in the management of psoriasis patients who are taking FAE s and who develop low absolute T‐cell counts.

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