Jeff and Penny Vinik Center for Allergic Disease Research, Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Division of General Internal Medicine and Primary Care, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
Division of General Internal Medicine and Primary Care, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
J Allergy Clin Immunol Pract. 2023 Feb;11(2):492-499.e2. doi: 10.1016/j.jaip.2022.11.001. Epub 2022 Nov 7.
Mas-related G protein-couple receptor x2 (Mrgprx2) activation underlies many common non-IgE-mediated adverse drug reactions (ADRs), yet the features of patients with reactions to Mrgprx2-activating drugs are unknown.
To characterize the patient-specific comorbidities and laboratory characteristics associated with listed reactions to Mrgprx2-activating drugs, including fluoroquinolones, morphine, neuromuscular blockade agents, vancomycin, and leuprolide.
We used a retrospective, observational cohort study design using electronic health record data from adults with an Mrgprx2-activating drug exposure recorded within a hospital system clinical Biobank. Odds ratios (ORs) and incidence rate ratios for clinical characteristics associated with ADRs, including immediate hypersensitivity reactions, were calculated using multivariable logistic regression.
Among 59,763 patients exposed to Mrgprx2-activating drugs, 4846 had a listed ADR. Female sex, White race, asthma (OR: 1.81, 95% confidence interval [CI]: 1.68-1.94), chronic urticaria (OR: 1.73, 95% CI: 1.46-2.05), and mastocytosis (OR: 12.79, 95% CI: 5.98-27.02) were associated with increased odds of a reaction. Overall, patients with allergic disease had 1.21 times the rate of an ADR compared with patients without allergic disease. Elevated absolute eosinophil count was inversely associated with reactions, and there was no association with elevated total IgE. Observed associations were similar in a patient subgroup with immediate-type hypersensitivity reactions.
Specific allergic diseases and common allergic biomarkers are differentially associated with ADRs to Mrgprx2-activating drugs. These findings from a large, "real world" drug-exposed population highlight clinical factors that may contribute to non-IgE-mediated drug allergy.
Mas 相关 G 蛋白偶联受体 x2(Mrgprx2)的激活是许多常见的非 IgE 介导的药物不良反应(ADR)的基础,但对 Mrgprx2 激活药物反应患者的特征尚不清楚。
描述与 Mrgprx2 激活药物(包括氟喹诺酮类、吗啡、神经肌肉阻滞药、万古霉素和亮丙瑞林)相关的患者特有的合并症和实验室特征。
我们使用回顾性、观察性队列研究设计,使用电子病历数据,来自在医院系统临床生物库中记录有 Mrgprx2 激活药物暴露的成年人。使用多变量逻辑回归计算与 ADR(包括即刻过敏反应)相关的临床特征的比值比(OR)和发病率比。
在 59763 名暴露于 Mrgprx2 激活药物的患者中,有 4846 名患者出现了上市 ADR。女性、白种人、哮喘(OR:1.81,95%置信区间[CI]:1.68-1.94)、慢性荨麻疹(OR:1.73,95% CI:1.46-2.05)和肥大细胞增多症(OR:12.79,95% CI:5.98-27.02)与反应的可能性增加相关。总体而言,与无过敏病史的患者相比,有过敏病史的患者 ADR 发生率增加了 1.21 倍。绝对嗜酸性粒细胞计数升高与反应呈负相关,而与总 IgE 升高无关。在即时型过敏反应的患者亚组中观察到的关联相似。
特定的过敏疾病和常见的过敏生物标志物与 Mrgprx2 激活药物的 ADR 有不同的关联。这些来自大型“真实世界”药物暴露人群的发现突出了可能导致非 IgE 介导的药物过敏的临床因素。