Department of Dermatology, Venereology and Allergology, Ruhr University Bochum, Bochum, Germany.
Institute of Medical Biometry and Informatics (IMBI), University Hospital Heidelberg, Heidelberg, Germany.
J Eur Acad Dermatol Venereol. 2019 May;33(5):893-905. doi: 10.1111/jdv.15448. Epub 2019 Feb 28.
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 of FAEs on lymphocytes.
To evaluate the influence of long-term FAE (Fumaderm ) treatment on peripheral blood CD4 and CD8 T cells, CD19 B cells and CD56 natural killer (NK) cells in psoriasis.
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.
FAEs significantly reduced the numbers of CD4 T, CD8 T, CD19 B and CD56 NK cells. Among lymphocyte subsets, the mean percentage reduction from baseline was always highest for CD8 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.
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 CD4 and CD8 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 FAEs and who develop low absolute T-cell counts.
富马酸酯（FAE）用于治疗银屑病，已知约 60%的患者会出现淋巴细胞减少症。FAE 对淋巴细胞的生物学影响仍有许多待阐明之处。
评估长期 FAE（Fumaderm）治疗对银屑病患者外周血 CD4 和 CD8 T 细胞、CD19 B 细胞和 CD56 自然杀伤（NK）细胞的影响。
在这项单中心回顾性观察性亚队列研究中，我们在 371 名银屑病患者（平均年龄 47.8 岁；63.3%为男性）开始 FAE 治疗前获得了白细胞和淋巴细胞亚群计数，并在治疗期间对其进行了监测（平均治疗时间为 2.9 年）。使用多参数流式细胞术进行免疫表型分析。
FAE 显著降低了 CD4 T、CD8 T、CD19 B 和 CD56 NK 细胞的数量。在淋巴细胞亚群中，从基线开始的平均百分比降低始终以 CD8 T 细胞最高，治疗 2 年后达到 55.7%的峰值。FAE 治疗开始时银屑病患者的年龄越大，T 细胞淋巴细胞减少症的风险就会显著增加。当与甲氨蝶呤和叶酸（维生素 B9）补充联合治疗时，该风险会显著降低。有证据表明 T 细胞淋巴细胞减少症增强了 FAE 治疗的效果。
监测不同的 T 细胞亚群而不仅仅是绝对淋巴细胞计数，可能会为 FAE 治疗的安全性和疗效提供更有意义的见解。因此，我们建议通过定期额外监测 CD4 和 CD8 T 细胞计数来优化药物警戒，尤其是在年龄较大的患者中。因此，需要进一步的前瞻性研究来建立基于证据的建议，以指导皮肤科医生管理接受 FAE 治疗且出现绝对 T 细胞计数较低的银屑病患者。
