Lin Lanmei, Wang Yilun, Lu Xiaonian, Wang Tianxiao, Li Qunyi, Wang Runnan, Wu Jinfeng, Xu Jinhua, Du Juan
Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai, China.
Department of Pharmacy, Huashan Hospital Affiliated to Fudan University, Shanghai, China.
Front Pharmacol. 2022 Jun 24;13:937490. doi: 10.3389/fphar.2022.937490. eCollection 2022.
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, = 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, = 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664, = 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.
银屑病是一种常见的免疫介导性炎症性皮肤病。尽管生物制剂在中重度银屑病的治疗中取得了良好的临床疗效，但继发性无反应（SNR）现象已逐渐被认识。SNR是指患者使用肿瘤坏死因子-α生物制剂等生物制剂达到临床缓解后疗效逐渐下降的情况。阿维A作为一种治疗银屑病的免疫调节性全身用药，可改善对生物制剂的SNR且耐受性良好，但疗效仍存在个体差异。许多相关炎性细胞因子的单核苷酸多态性（SNP）已被证明是银屑病药物反应个体差异的重要因素，但关于利用药物基因组学缓解对生物制剂的SNR的报道较少。本研究招募了43例银屑病患者和24例正常对照，以研究炎性细胞因子的SNP是否可作为阿维A缓解银屑病患者对肿瘤坏死因子-α生物制剂的SNR的生物标志物，包括rs1800795（IL-6）、rs6887695（IL-12b）、rs3212227（IL-12b）、rs10484879（IL-17a）、rs4819554（IL-17ra）、rs763780（IL-17F）、rs11209032（IL23R）、rs11209026（IL23R）和rs2201841（IL23R）。该研究还分析了上述SNP与仅使用阿维A患者疗效之间的相关性，以了解改善是归因于阿维A对SNR的干预还是阿维A的单纯反应。我们发现，在SNP rs112009032（IL-23R）处为纯合子AA（χ2 = 6.577，P = 0.02）的患者中，阿维A可改善对肿瘤坏死因子α单克隆抗体的SNR。在rs3212227（IL-12B）处基因型为TG（χ2 = 6.124，P = 0.035）的患者在使用阿维A治疗银屑病时更敏感。rs3212227（χ2 = 7.664，P = 0.022）也与银屑病易感性相关。该研究可能为银屑病生物制剂继发性反应丧失的个性化治疗提供临床决策参考。
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