4th Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
2nd Department of Dermatology and Venereology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Dermatology. 2023;239(5):746-752. doi: 10.1159/000531558. Epub 2023 Jun 16.
Results of randomized clinical trials show great variation in response to treatment with adalimumab (ADA) in hidradenitis suppurativa (HS). This varied response may be associated with genetic polymorphisms.
The aim of the study was to study the association between carriage of single nucleotide polymorphisms (SNPs) in the promoter of the tumor necrosis factor (TNF) gene and their response to ADA.
Patients with moderate to severe HS who received ADA treatment for at least 12 weeks were enrolled. SNPs were analyzed with PCR-restriction fragment length polymorphism. Hidradenitis Suppurativa Clinical Response (HiSCR) score, International Hidradenitis Suppurativa Severity Scoring System 4 (IHS4) score, inflammatory lesion (AN) count, and draining tunnel (dT) count were collected at weeks 0, 12, 24, 36, and 48.
HiSCR response after 12 weeks of ADA treatment was 71.8% among carriers of the common GGG haplotype and 50.0% among carriers of minor frequency SNP haplotypes (p: 0.031; odds ratio: 0.39). This significant difference persisted until week 36. Carriers of minor frequency SNP haplotypes also had a lower relative decrease of the AN count at weeks 12 and 24; the dT count and IHS4 were not statistically different between the two groups.
Carriage of at least one minor frequency SNP haplotype of the promoter of the TNF gene is associated with a decreased response to ADA. This association may have an impact on treatment decision-making.
随机临床试验的结果表明,阿达木单抗(ADA)治疗化脓性汗腺炎的反应差异很大。这种差异反应可能与遗传多态性有关。
本研究旨在研究肿瘤坏死因子(TNF)基因启动子中单核苷酸多态性(SNP)的携带情况及其与 ADA 反应的关系。
纳入至少接受 ADA 治疗 12 周的中重度化脓性汗腺炎患者。采用 PCR-限制性片段长度多态性分析 SNP。在 0、12、24、36 和 48 周时收集化脓性汗腺炎临床反应(HiSCR)评分、国际化脓性汗腺炎严重程度评分系统 4(IHS4)评分、炎症病变(AN)计数和引流隧道(dT)计数。
ADA 治疗 12 周后,常见 GGG 单倍型携带者的 HiSCR 反应为 71.8%,少见频率 SNP 单倍型携带者为 50.0%(p:0.031;优势比:0.39)。这种显著差异一直持续到第 36 周。少见频率 SNP 单倍型携带者在第 12 和第 24 周时的 AN 计数相对减少也较低;两组间 dT 计数和 IHS4 无统计学差异。
TNF 基因启动子至少携带一种少见频率 SNP 单倍型与 ADA 反应降低相关。这种关联可能对治疗决策产生影响。