Department of Clinical and Experimental Medicine, Section of Pediatrics, University of Pisa, Pisa, Italy; Department of Clinical Immunology and Allergology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia; Allergy and Immunology Department, Children's Hospital Colorado, Aurora, Colo.
Allergy and Immunology Department, Children's Hospital Colorado, Aurora, Colo.
J Allergy Clin Immunol Pract. 2019 Nov-Dec;7(8):2689-2696.e2. doi: 10.1016/j.jaip.2019.05.053. Epub 2019 Jun 13.
Mepolizumab is an anti-IL-5 antibody approved for the treatment of severe eosinophilic asthma. However, the prevalence of patients with severe asthma eligible for mepolizumab remains unknown, especially among children.
To determine, in a population of patients with severe asthma from a tertiary referral center, the proportion of patients with an eosinophilic phenotype who would be eligible for mepolizumab, when stratified for the age of onset of asthma, and the prevalence of phenotypic features that favor mepolizumab therapy.
An extensive database of 245 adults and children referred for severe asthma was used. The prevalence of severe asthma was estimated by using the European Respiratory Society/American Thoracic Society criteria. Patients with an eosinophilic uncontrolled phenotype qualified for mepolizumab.
In our cohort, 216 (88%) had severe asthma. Based on blood eosinophils of either greater than or equal to 150 cells/μL or greater than or equal to 300 cells/μL, 61%/41% had an eosinophilic phenotype, while 49%/34% were eligible for mepolizumab therapy. A greater percentage of adults (60%/47% of adults with asthma onset in adulthood [AoA] and 48%/26% adults with childhood-onset asthma [<18 years, CoA]) were eligible compared with children (33%/24%), for eosinophil counts of ≥150 and ≥300 cells/μL, respectively; P < .05. Compared with adults, children had a similar number of exacerbations while having better lung function (P < .05). Among adults, those with AoA were older, were more likely to have nasal polyps (28% vs 5%; P < .05), and had higher blood eosinophil counts (272 vs 150 cells/μL; P < .05) compared with those with CoA, with no difference in lung function noted between the 2 groups. Subjects showing greater than or equal to 500 eosinophils/μL, a strong indicator for mepolizumab therapy, had more nasal polyps, higher inhaled steroid dose, lower lung function, and AoA predominance than did those with less than 500 eosinophils/μL (P < .05).
A smaller percentage of children with severe asthma were eligible for mepolizumab compared with their adult peers. Severe AoA has distinct phenotypic features that favor treatment with mepolizumab, including greater eosinophilia and nasal polyposis, in contrast to CoA, which appears to have fewer features of type 2 mucosal inflammation.
美泊利珠单抗是一种抗白细胞介素-5 抗体,已被批准用于治疗严重嗜酸性粒细胞性哮喘。然而,适合接受美泊利珠单抗治疗的严重哮喘患者的患病率,尤其是儿童患者,尚不清楚。
在一家三级转诊中心的严重哮喘患者人群中,确定根据哮喘发病年龄分层的嗜酸性粒细胞表型患者中,有多少比例的患者适合接受美泊利珠单抗治疗,并确定有利于美泊利珠单抗治疗的表型特征的患病率。
使用了一个包含 245 名成人和儿童患者的广泛数据库,这些患者因严重哮喘而被转诊。使用欧洲呼吸学会/美国胸科学会的标准来估计严重哮喘的患病率。具有嗜酸性粒细胞未控制表型的患者有资格接受美泊利珠单抗治疗。
在我们的队列中,216 名(88%)患者患有严重哮喘。根据血液嗜酸性粒细胞计数≥150 细胞/μL 或≥300 细胞/μL,61%/41%的患者具有嗜酸性粒细胞表型,而 49%/34%的患者适合接受美泊利珠单抗治疗。与儿童相比,更大比例的成年人(成年发病[AoA]的成年人中为 60%/47%,儿童发病[<18 岁,CoA]的成年人中为 48%/26%)符合嗜酸性粒细胞计数≥150 和≥300 细胞/μL 的条件;P<0.05。与成年人相比,儿童的哮喘加重次数相似,但肺功能更好(P<0.05)。在成年人中,AoA 患者年龄更大,更有可能患有鼻息肉(28%比 5%;P<0.05),且血液嗜酸性粒细胞计数更高(272 比 150 细胞/μL;P<0.05),但两组之间的肺功能没有差异。与嗜酸性粒细胞计数<500 细胞/μL 的患者相比,嗜酸性粒细胞计数≥500 细胞/μL 的患者具有更多的鼻息肉、更高的吸入性皮质类固醇剂量、更低的肺功能和 AoA 优势,这些都是美泊利珠单抗治疗的强烈指征(P<0.05)。
与成年患者相比,患有严重哮喘的儿童患者适合接受美泊利珠单抗治疗的比例较小。严重的 AoA 具有明显的表型特征,有利于接受美泊利珠单抗治疗,包括更高的嗜酸性粒细胞增多和鼻息肉形成,而与 CoA 相反,CoA 似乎较少具有 2 型黏膜炎症的特征。