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The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis

Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of effica...

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Autores principales: Lin, Lanmei, Wang, Yilun, Lu, Xiaonian, Wang, Tianxiao, Li, Qunyi, Wang, Runnan, Wu, Jinfeng, Xu, Jinhua, Du, Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263382/
https://www.ncbi.nlm.nih.gov/pubmed/35814239
http://dx.doi.org/10.3389/fphar.2022.937490
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author Lin, Lanmei
Wang, Yilun
Lu, Xiaonian
Wang, Tianxiao
Li, Qunyi
Wang, Runnan
Wu, Jinfeng
Xu, Jinhua
Du, Juan
author_facet Lin, Lanmei
Wang, Yilun
Lu, Xiaonian
Wang, Tianxiao
Li, Qunyi
Wang, Runnan
Wu, Jinfeng
Xu, Jinhua
Du, Juan
author_sort Lin, Lanmei
collection PubMed
description Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of efficacy after the patient achieves clinical remission with biological agents such as TNF-α biologics. Acitretin, as an immunomodulatory systemic drug for psoriasis, can improve the SNR to biological agents with good tolerance, but there are still individual differences in efficacy. Single-nucleotide polymorphisms (SNPs) of many related inflammatory cytokines have been shown to be important factors of individual differences in drug response in psoriasis, but there have been few reports on the use of pharmacogenomics to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF-α biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (χ2 = 6.577, p = 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNFα monoclonal antibody. Patients with the genotype of TG (χ2 = 6.124, p = 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664, p = 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics.
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spelling pubmed-92633822022-07-09 The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis Lin, Lanmei Wang, Yilun Lu, Xiaonian Wang, Tianxiao Li, Qunyi Wang, Runnan Wu, Jinfeng Xu, Jinhua Du, Juan Front Pharmacol Pharmacology Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of efficacy after the patient achieves clinical remission with biological agents such as TNF-α biologics. Acitretin, as an immunomodulatory systemic drug for psoriasis, can improve the SNR to biological agents with good tolerance, but there are still individual differences in efficacy. Single-nucleotide polymorphisms (SNPs) of many related inflammatory cytokines have been shown to be important factors of individual differences in drug response in psoriasis, but there have been few reports on the use of pharmacogenomics to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF-α biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (χ2 = 6.577, p = 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNFα monoclonal antibody. Patients with the genotype of TG (χ2 = 6.124, p = 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664, p = 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics. Frontiers Media S.A. 2022-06-24 /pmc/articles/PMC9263382/ /pubmed/35814239 http://dx.doi.org/10.3389/fphar.2022.937490 Text en Copyright © 2022 Lin, Wang, Lu, Wang, Li, Wang, Wu, Xu and Du. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Lin, Lanmei
Wang, Yilun
Lu, Xiaonian
Wang, Tianxiao
Li, Qunyi
Wang, Runnan
Wu, Jinfeng
Xu, Jinhua
Du, Juan
The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis
title The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis
title_full The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis
title_fullStr The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis
title_full_unstemmed The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis
title_short The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis
title_sort inflammatory factor snp may serve as a promising biomarker for acitretin to alleviate secondary failure of response to tnf-a monoclonal antibodies in psoriasis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263382/
https://www.ncbi.nlm.nih.gov/pubmed/35814239
http://dx.doi.org/10.3389/fphar.2022.937490
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