Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis

Background Fumaric acid esters (FAEs) 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 ofFAEs on lymphocytes. Objective To evaluate the influence of long‐termFAE(Fumaderm®) treatment on peripheral bloodCD4+andCD8+T cells,CD19+B cells andCD56+natural killer (NK) cells in psoriasis. Methods In this single‐centre retrospective observational subcohort study, we obtained leucocyte and lymphocyte subset counts before initiatingFAEtherapy 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 FAEs significantly reduced the numbers ofCD4+T,CD8+T,CD19+B andCD56+NKcells. Among lymphocyte subsets, the mean percentage reduction from baseline was always highest forCD8+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 thatFAEtherapy 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 ofFAEtherapy. Conclusions Monitoring distinct T‐cell subsets rather than just absolute lymphocyte counts may provide more meaningful insights into both theFAEtreatment safety and efficacy. We therefore suggest optimizing pharmacovigilance by additionally monitoringCD4+andCD8+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 takingFAEs and who develop low absolute T‐cell counts.