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奥马珠单抗在特应性哮喘中的药物留存率:临床和基因变量的影响

Drug survival of omalizumab in atopic asthma: Impact of clinical and genetic variables.

作者信息

Rojo-Tolosa Susana, Caballero-Vázquez Alberto, Pineda-Lancheros Laura E, Sánchez-Martínez José A, González-Gutiérrez María V, Jiménez-Gálvez Gonzalo, Jiménez-Morales Alberto, Morales-García Concepción

机构信息

Respiratory Medicine Department, University Hospital Virgen de las Nieves, Granada, Spain.

Pharmacogenetics Unit, Pharmacy Service, University Hospital Virgen de las Nieves, Granada, Spain.

出版信息

Hum Vaccin Immunother. 2025 Dec;21(1):2488557. doi: 10.1080/21645515.2025.2488557. Epub 2025 Apr 6.

DOI:10.1080/21645515.2025.2488557
PMID:40189906
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12054927/
Abstract

It is estimated that 40-50% of severe asthma has an atopic basis, representing a clinical challenge and a significant economic burden for healthcare systems. The most effective treatment has emerged with the use of biologic therapies such as omalizumab; however, the rate of therapy switching due to loss of efficacy is high, which has a negative impact on the healthcare system. The aim was to evaluate the influence of genetic polymorphisms as predictors of omalizumab survival. We conducted a retrospective observational cohort study of 110 patients with uncontrolled severe allergic asthma treated with omalizumab in a tertiary hospital. We analyzed (rs2251746, rs2427837), (rs1441586, rs573790, rs1054485, rs569108), (rs2230199), FCGR2A (rs1801274), (rs3219018, rs1050501), (rs10127939, rs396991), (rs1420101, rs17026974, rs1921622) and (rs4857855) by real-time PCR using Taqman probes. Drug survival was defined as the time from initiation to discontinuation of omalizumab. Cox regression analysis adjusted for the presence of respiratory disease, GERD, SAHS and years with asthma showed that the SNPs rs573790 - CT ( < .001; HR = 3.38; CI95% = 1.66-6.87), rs10127939-AC ( = .018; HR = 3.85; CI95% = 1.25-11.81) and rs396991-CC ( = .020; HR = 2.23; CI95% = 1.14-4.38) were the independent variables associated with worse survival in patients diagnosed with asthma. A trend toward statistical significance was also found between and rs10127939-CC ( = .080; HR = 0.13; CI95% = 0.01-1.28) and longer drug survival. The results of this study demonstrate the potential influence of the polymorphisms studied on omalizumab survival and the clinical benefit that could be achieved by defining predictive biomarkers of drug survival.

摘要

据估计,40%-50%的重度哮喘有特应性基础,这对医疗系统构成了临床挑战和巨大的经济负担。使用诸如奥马珠单抗等生物疗法已出现了最有效的治疗方法;然而,由于疗效丧失导致的治疗转换率很高,这对医疗系统产生了负面影响。目的是评估基因多态性作为奥马珠单抗治疗持续时间预测指标的影响。我们在一家三级医院对110例接受奥马珠单抗治疗的未控制的重度过敏性哮喘患者进行了一项回顾性观察队列研究。我们使用Taqman探针通过实时聚合酶链反应分析了(rs2251746,rs2427837)、(rs1441586,rs573790,rs1054485,rs569108)、(rs2230199)、FCGR2A(rs1801274)、(rs3219018,rs1050501)、(rs10127939,rs396991)、(rs1420101,rs17026974,rs1921622)和(rs4857855)。药物治疗持续时间定义为从开始使用奥马珠单抗到停药之间的时间。针对呼吸系统疾病、胃食管反流病、睡眠呼吸暂停低通气综合征的存在情况以及哮喘病程进行校正的Cox回归分析表明,单核苷酸多态性rs573790 - CT(P<0.001;风险比=3.38;95%置信区间=1.66-6.87)、rs10127939-AC(P=0.018;风险比=3.85;95%置信区间=1.25-11.81)和rs396991-CC(P=0.020;风险比=2.23;95%置信区间=1.14-4.38)是与哮喘诊断患者较差的治疗持续时间相关的独立变量。在rs10127939-CC与更长的药物治疗持续时间之间也发现了具有统计学意义的趋势(P=0.080;风险比=0.13;95%置信区间=0.01-1.28)。本研究结果证明了所研究的多态性对奥马珠单抗治疗持续时间的潜在影响,以及通过定义药物治疗持续时间的预测生物标志物可实现的临床益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/ddd767fa1811/KHVI_A_2488557_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/4d26a9b92df9/KHVI_A_2488557_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/61cf5cf1942f/KHVI_A_2488557_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/3c0e0b9e9df1/KHVI_A_2488557_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/99dc50598e52/KHVI_A_2488557_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/24cd6a17bcd1/KHVI_A_2488557_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/ddd767fa1811/KHVI_A_2488557_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/4d26a9b92df9/KHVI_A_2488557_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/61cf5cf1942f/KHVI_A_2488557_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/3c0e0b9e9df1/KHVI_A_2488557_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/99dc50598e52/KHVI_A_2488557_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/24cd6a17bcd1/KHVI_A_2488557_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c77/12054927/ddd767fa1811/KHVI_A_2488557_F0006_OC.jpg

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本文引用的文献

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[A Study of the Prevalence of Asthma in the General Population in Spain].[西班牙普通人群哮喘患病率研究]
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Impact of Functional Polymorphisms on Drug Survival of Biological Therapies in Patients with Moderate-to-Severe Psoriasis.
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Int J Mol Sci. 2023 May 12;24(10):8703. doi: 10.3390/ijms24108703.
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Influence of Genetics on the Response to Omalizumab in Patients with Severe Uncontrolled Asthma with an Allergic Phenotype.遗传学对过敏性表型的重度未控制哮喘患者奥马珠单抗应答的影响。
Int J Mol Sci. 2023 Apr 10;24(8):7029. doi: 10.3390/ijms24087029.
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Rev Med Inst Mex Seguro Soc. 2022 Mar 1;60(2):201-210.
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Eur Respir J. 2022 Nov 10;60(5). doi: 10.1183/13993003.03130-2021. Print 2022 Nov.
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Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline.重度哮喘的管理:欧洲呼吸学会/美国胸科学会指南
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