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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 of FAEs on lymphocytes. OBJECTIVE: To evaluate the influence of long‐term FAE (Fumaderm(®)) treatment on pe...

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Autores principales: Dickel, H., Bruckner, T., Höxtermann, S., Dickel, B., Trinder, E., Altmeyer, P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593701/
https://www.ncbi.nlm.nih.gov/pubmed/30680823
http://dx.doi.org/10.1111/jdv.15448
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author Dickel, H.
Bruckner, T.
Höxtermann, S.
Dickel, B.
Trinder, E.
Altmeyer, P.
author_facet Dickel, H.
Bruckner, T.
Höxtermann, S.
Dickel, B.
Trinder, E.
Altmeyer, P.
author_sort Dickel, H.
collection PubMed
description 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 of FAEs on lymphocytes. OBJECTIVE: 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. 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: 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. 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 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.
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spelling pubmed-65937012019-07-10 Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis Dickel, H. Bruckner, T. Höxtermann, S. Dickel, B. Trinder, E. Altmeyer, P. J Eur Acad Dermatol Venereol 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 of FAEs on lymphocytes. OBJECTIVE: 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. 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: 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. 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 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. John Wiley and Sons Inc. 2019-02-28 2019-05 /pmc/articles/PMC6593701/ /pubmed/30680823 http://dx.doi.org/10.1111/jdv.15448 Text en © 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Psoriasis
Dickel, H.
Bruckner, T.
Höxtermann, S.
Dickel, B.
Trinder, E.
Altmeyer, P.
Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis
title Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis
title_full Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis
title_fullStr Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis
title_full_unstemmed Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis
title_short Fumaric acid ester‐induced T‐cell lymphopenia in the real‐life treatment of psoriasis
title_sort fumaric acid ester‐induced t‐cell lymphopenia in the real‐life treatment of psoriasis
topic Psoriasis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593701/
https://www.ncbi.nlm.nih.gov/pubmed/30680823
http://dx.doi.org/10.1111/jdv.15448
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