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HLA-B*15：02阴性患者发生抗癫痫药物相关严重皮肤不良反应的非遗传风险因素研究
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| 篇名： | HLA-B*15：02阴性患者发生抗癫痫药物相关严重皮肤不良反应的非遗传风险因素研究 |
| TITLE： | Study on non-genetic risk factors for antiepileptic drug-induced severe cutaneous adverse reactions in HLA-B*15：02 negative patients |
| 摘要： | 目的 分析HLA-B*15：02阴性患者发生抗癫痫药物（AEDs）相关严重皮肤不良反应（SCARs）的非遗传风险因素，为临床精准用药提供依据。方法采用回顾性病例对照设计，纳入2022年1月至2024年12月在我院行HLA-B*15：02检测的患者，将患者分为SCARs组（HLA-B*15：02阴性且被诊断为SCARs，15例）和对照组（HLA-B*15：02阴性的AEDs使用者，38例）。通过单因素分析与多因素Firth惩罚似然逻辑回归模型（Firth回归）评估风险因素，并采用Benjamini-Hochberg错误发现率（FDR）和Firth回归进行校正，采用敏感性分析以量化对照组中卡马西平暴露率可能存在的偏倚对结果的影响。结果单因素分析结果显示，年龄≥50岁、服用卡马西平、联合使用抗生素/抗病毒药物为发生AEDs相关SCARs的危险因素（OR分别为18.15、7.54、13.46，95%CI分别为4.13～79.84、1.89～30.08、1.36～133.18，均P＜0.05），服用拉莫三嗪为保护因素[OR为0.10，95%CI为0.02～0.39，P＜0.05）。经FDR校正后，上述因素仍保持统计学显著性（P＜0.05）。多因素分析结果显示，年龄≥50岁（校正后OR为16.27，95%CI为3.98～66.55，P＜0.001）和服用卡马西平（校正后OR为7.11，95%CI为1.82～27.85，P＝0.005）均是发生AEDs相关SCARs的独立危险因素。敏感性分析结果显示，校正后服用卡马西平的风险OR范围在14.2～28.4之间。结论在HLA-B*15：02阴性患者中，年龄≥50岁和服用卡马西平是发生AEDs相关SCARs的独立非遗传风险因素。建议高龄患者优先选用卡马西平以外的AEDs。 |
| ABSTRACT： | OBJECTIVE To analyze the non-genetic risk factors for severe cutaneous adverse reactions （SCARs） related to antiepileptic drugs （AEDs） in HLA-B*15：02 negative patients， and provide a basis for clinical precision medication. METHODS A retrospective case-control design was used to include patients who underwent HLA-B*15：02 testing at our hospital from January 2022 to December 2024. Patients were divided into SCARs group （15 cases who were HLA-B*15：02 negative and diagnosed with SCARs） and control group （38 cases who were HLA-B*15：02 negative and used AEDs）. Risk factors were evaluated using univariate analysis and a multivariable Firth penalty likelihood logistic regression model （Firth regression）， and Benjamin-Hochberg false discovery rate （FDR） and Firth regression were used for correction， and sensitivity analysis was used to quantify the impact of potential biases in carbamazepine exposure rates in the control group on the results. RESULTS Univariate analysis showed that age≥50 years， use of carbamazepine， and combination use of antibiotics/antiviral drugs were risk factors for developing AEDs- related SCARs （OR＝18.15， 7.54， 13.46， 95%CI of 4.13-79.84， 1.89-30.08， 1.36-133.18， all P＜0.05）， while taking lamotrigine was a protective factor [OR＝0.10， 95%CI of 0.02-0.39， P＜0.05]. After FDR correction， the above factors still maintained statistical significance （P＜0.05）. The results of multivariate analysis showed that age≥50 years [adjusted OR＝16.27， 95%CI of 3.98-66.55， P＜0.001] and taking carbamazepine [adjusted OR＝7.11， 95%CI of 1.82-27.85， P＝0.005] were independent risk factors for the occurrence of SCARs-related AEDs. The results of sensitivity analysis showed that the adjusted risk OR range for taking carbamazepine was between 14.2 and 28.4. CONCLUSIONS Age≥50 years and use of carbamazepine are independent non- genetic risk factors for the development of SCARs-related AEDs in HLA-B*15：02 negative patients. It is recommended that elderly patients should prioritize the use of AEDs other than carbamazepine. |
| 期刊： | 2025年第36卷第24期 |
| 作者： | 邓明影；杨本军；冯晓俊；唐丽琴 |
| AUTHORS： | DENG Mingying，YANG Benjun，FENG Xiaojun，TANG Liqin |
| 关键字： | 抗癫痫药物；严重皮肤不良反应；HLA-B*15：02阴性；风险因素 |
| KEYWORDS： | antiepileptic drugs； severe cutaneous adverse |
| 阅读数： | 3 次 |
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