Allianz Research Institute, 14120 Beach Blvd, Suite 101, Westminster, CA, USA.
J Med Case Rep. 2021 Mar 6;15(1):103. doi: 10.1186/s13256-021-02663-2.
T cell-mediated eosinophilia is associated with numerous conditions-including atopic dermatitis, food allergies, and asthma-collectively known as the "atopic march." Benralizumab is a recombinant, humanized, afucosylated monoclonal antibody directed against the ⍺ chain of the eosinophil cell surface receptor IL-5R. Benralizumab treatment causes near-complete depletion of circulating eosinophils and was approved in 2017 for add-on, maintenance treatment of severe asthma with an eosinophilic phenotype, based on the results of the CALIMA and SIROCCO pivotal trials. Benralizumab is not currently approved for the treatment of eosinophilic conditions besides asthma; however, during the CALIMA trial, spontaneous resolution of atopic dermatitis was observed in a patient, concurrent with reduction in her asthma symptoms.
In January 2015, a 14-year-old Asian girl with severe, uncontrolled asthma was enrolled in CALIMA. The patient's baseline eosinophil blood count was 1200 cells/μL, her pre-bronchodilator forced expiratory volume in 1 second (FEV) was 1.9 L and FEV/forced vital capacity (FVC) ratio was 71.4%, and her post-bronchodilator FEV was 3.2 L (FEV/FVC of 115.9%). Her overall baseline asthma symptom score was 3.9 and her asthma exacerbation rate in the prior year was 4. She also displayed a pronounced, pruritic, chronic, inflammatory rash consistent with atopic dermatitis across her face. The investigator was blinded to the patient's treatment group during treatment; however, her asthma symptoms diminished over the course of the study (FEV at 56 weeks, 3.01 L/110.5% (pre) and 3.25 L/119.3% (post); overall asthma symptom score 2.1; one influenza-associated exacerbation). Furthermore, her atopic dermatitis symptoms resolved spontaneously within the first 5 months of the study. After unblinding, the patient was confirmed to have been randomized to an active treatment arm, and her blood eosinophil count had dropped below the limit of detection after the first study dose.
Given the potential shared mechanisms between eosinophilic asthma and atopic dermatitis, it is plausible that benralizumab-induced eosinopenia factored into the resolution of the patient's atopic dermatitis. Further clinical studies are warranted to determine whether benralizumab or other drugs targeted against IL-5/IL-5R may be useful in managing multiple conditions associated with eosinophilia.
T 细胞介导的嗜酸性粒细胞增多与多种疾病相关,包括特应性皮炎、食物过敏和哮喘,这些疾病统称为“特应性进程”。贝那鲁肽是一种针对嗜酸性粒细胞表面受体 IL-5R ⍺ 链的重组人源化去岩藻糖基化单克隆抗体。贝那鲁肽治疗可导致循环嗜酸性粒细胞几乎完全耗竭,基于 CALIMA 和 SIROCCO 关键试验结果,于 2017 年被批准用于伴有嗜酸性粒细胞表型的重度哮喘的附加维持治疗。贝那鲁肽目前尚未被批准用于治疗哮喘以外的嗜酸性粒细胞疾病;然而,在 CALIMA 试验中,一名患者的特应性皮炎自发缓解,同时哮喘症状减轻。
2015 年 1 月,一名 14 岁的亚裔女孩患有严重的、未控制的哮喘,被纳入 CALIMA 研究。患者的基线嗜酸性粒细胞血计数为 1200 个/μL,其支气管扩张剂预前用力呼气量(FEV1)为 1.9 L,FEV/FVC 比值为 71.4%,支气管扩张剂后 FEV1 为 3.2 L(FEV/FVC 为 115.9%)。她的总体基线哮喘症状评分为 3.9,前一年哮喘加重率为 4 次。她还表现出明显的、瘙痒的、慢性的、炎症性皮疹,符合特应性皮炎,皮疹遍布她的面部。在治疗期间,研究者对患者的治疗组不知情;然而,她的哮喘症状在研究过程中逐渐减轻(56 周时的 FEV1,3.01 L/110.5%(预)和 3.25 L/119.3%(后);总体哮喘症状评分 2.1;1 次流感相关加重)。此外,她的特应性皮炎症状在研究的前 5 个月内自发缓解。在揭盲后,患者被证实被随机分配到活性治疗组,她的血液嗜酸性粒细胞计数在第一次研究剂量后降至检测下限以下。
鉴于嗜酸性粒细胞性哮喘和特应性皮炎之间可能存在共同的发病机制,贝那鲁肽诱导的嗜酸性粒细胞减少可能是患者特应性皮炎缓解的原因之一。需要进一步的临床研究来确定贝那鲁肽或其他针对 IL-5/IL-5R 的药物是否可用于治疗与嗜酸性粒细胞增多相关的多种疾病。