Eileen Wang, William Henley, Désirée Larenas-Linnemann, Lakmini Bulathsinhala, Trung N Tran, Michael E Wechsler, Shawn D Aaron, Mona Al-Ahmad, Riyad Al-Lehebi, Alan Altraja, Peter Barker, Aaron Beastall, Andrey S Belevskiy, Celine Bergeron, Leif Bjermer, Unnur S Björnsdóttir, Sinthia Z Bosnic-Anticevich, Arnaud Bourdin, Guy G Brusselle, John Busby, Giorgio Walter Canonica, Victoria Carter, Kenneth R Chapman, Nicholas Chapman, George C Christoff, Borja G Cosio, Richard W Costello, James Fingleton, João A Fonseca, Mina Gaga, Peter G Gibson, Susanne Hansen, Liam G Heaney, Enrico Heffler, Mark Hew, Takahiko Horiguchi, Flavia Hoyte, Richard B Hubbard, Takashi Iwanaga, David J Jackson, Rohit Katial, Mariko Siyue Koh, Konstantinos Kostikas, Piotr Kuna, Sverre Lehmann, Lauri Lehtimäki, Renaud Louis, Dóra Lúdvíksdóttir, Njira Lugogo, Bassam Mahboub, Neil Martin, Jorge Máspero, Andrew N Menzies-Gow, Arjun Mohan, Ruth B Murray, Tatsuya Nagano, Nikolaos G Papadopoulos, Andriana I Papaioannou, Pujan H Patel, Luis Perez-de-Llano, Diahn-Warng Perng, Matthew J Peters, Paul E Pfeffer, Paulo Márcio Pitrez, Roy Alton Pleasants, Todor A Popov, Celeste M Porsbjerg, Francesca Puggioni, Anna Quinton, Chin Kook Rhee, Mohsen Sadatsafavi, Sundeep Salvi, Giulia Scioscia, Chau-Chyun Sheu, Concetta Sirena, Camille Taillé, Christian Taube, Carlos A Torres-Duque, Ming-Ju Tsai, Alf Tunsäter, Charlotte Suppli Ulrik, David B Price
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Biomarker distribution (blood eosinophil count, fractional exhaled nitric oxide, and IgE) was quantified before biologic initiation. Clusters were identified using a 5-component Gaussian finite mixture model and phenotypically characterized. Changes in asthma and health care utilization outcomes between 1-year pre- and postbiologic initiation were compared between clusters and by biologic class.</p><p><strong>Results: </strong>Among 3675 patients, 5 biomarker clusters were identified along a gradient of T2 involvement: cluster A with the lowest T2 involvement (16.4%), cluster B (20.4%), cluster C (22.9%), cluster D (30.3%), and cluster E with the highest T2 involvement (10.0%). In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater increase in forced expiratory volume in 1 second compared with cluster A (difference 0.16 L [95% confidence interval: 0.08, 0.25]; P < .001). The odds of uncontrolled asthma were approximately 0.6 for all clusters compared with cluster A. Overall, exacerbation rates were lower, and greater improvements in lung function and asthma control were noted for anti-IL-5/5 receptor (R) (but not anti-IgE or anti-IL-4Rα) for all clusters compared with cluster A.</p><p><strong>Conclusion: </strong>T2-targeting biologics have utility in the management of asthma with low T2 involvement, but more effective therapies are needed. 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引用次数: 0
摘要
背景：对低水平t2生物标志物的哮喘了解甚少。目的：描述严重哮喘的表型特征，并沿着t2受累的梯度比较哮喘结局的生物学前和生物学后变化。方法：这是一项基于登记的队列研究，包括来自24个国家的数据。生物标志物分布（BEC, FeNO, IgE）在生物起始前被量化。使用五组分高斯有限混合模型识别聚类并进行表型表征。在1年内，哮喘和医疗保健利用结果的变化在生物制剂开始前后进行了分组和按生物制剂类别的比较。结果：在3,675例患者中，沿t2受累程度的梯度确定了5个生物标志物簇：a簇t2受累最低（16.4%），B簇（20.4%），C簇（22.9%），D簇（30.3%）和E簇t2受累最高（10.0%）。在多变量分析中，生物制剂的使用与所有群集的预后改善相关，但在T2谱的高端往往更好。例如，C类患者的FEV1明显高于a类患者（差异0.16L [95% CI 0.08, 0.25]）。结论：T2靶向生物制剂在低T2累及的哮喘治疗中具有实用价值，但需要更有效的治疗方法。需要进一步的研究来确定T2谱低端的特定致病途径，这些途径可以被生物制剂有效靶向。
Response to Biologics Along a Gradient of T2 Involvement in Patients With Severe Asthma: A Data-Driven Biomarker Clustering Approach.
Background: Asthma with low levels of type 2 (T2) biomarkers is poorly understood.
Objective: To characterize severe asthma phenotypes and compare changes in asthma outcomes from pre- to postbiologic treatment along a gradient of T2 involvement.
Methods: This was a registry-based cohort study including data from 24 countries. Biomarker distribution (blood eosinophil count, fractional exhaled nitric oxide, and IgE) was quantified before biologic initiation. Clusters were identified using a 5-component Gaussian finite mixture model and phenotypically characterized. Changes in asthma and health care utilization outcomes between 1-year pre- and postbiologic initiation were compared between clusters and by biologic class.
Results: Among 3675 patients, 5 biomarker clusters were identified along a gradient of T2 involvement: cluster A with the lowest T2 involvement (16.4%), cluster B (20.4%), cluster C (22.9%), cluster D (30.3%), and cluster E with the highest T2 involvement (10.0%). In multivariable analysis, biologic use was associated with improved outcomes in all clusters but tended to be better at the higher end of the T2 spectrum. For example, patients in cluster C had a significantly greater increase in forced expiratory volume in 1 second compared with cluster A (difference 0.16 L [95% confidence interval: 0.08, 0.25]; P < .001). The odds of uncontrolled asthma were approximately 0.6 for all clusters compared with cluster A. Overall, exacerbation rates were lower, and greater improvements in lung function and asthma control were noted for anti-IL-5/5 receptor (R) (but not anti-IgE or anti-IL-4Rα) for all clusters compared with cluster A.
Conclusion: T2-targeting biologics have utility in the management of asthma with low T2 involvement, but more effective therapies are needed. Further research is warranted to identify specific pathogenic pathways at the lower end of the T2 spectrum that can be effectively targeted by biologics.
期刊介绍：
JACI: In Practice is an official publication of the American Academy of Allergy, Asthma & Immunology (AAAAI). It is a companion title to The Journal of Allergy and Clinical Immunology, and it aims to provide timely clinical papers, case reports, and management recommendations to clinical allergists and other physicians dealing with allergic and immunologic diseases in their practice. The mission of JACI: In Practice is to offer valid and impactful information that supports evidence-based clinical decisions in the diagnosis and management of asthma, allergies, immunologic conditions, and related diseases.
This journal publishes articles on various conditions treated by allergist-immunologists, including food allergy, respiratory disorders (such as asthma, rhinitis, nasal polyps, sinusitis, cough, ABPA, and hypersensitivity pneumonitis), drug allergy, insect sting allergy, anaphylaxis, dermatologic disorders (such as atopic dermatitis, contact dermatitis, urticaria, angioedema, and HAE), immunodeficiency, autoinflammatory syndromes, eosinophilic disorders, and mast cell disorders.
The focus of the journal is on providing cutting-edge clinical information that practitioners can use in their everyday practice or to acquire new knowledge and skills for the benefit of their patients. However, mechanistic or translational studies without immediate or near future clinical relevance, as well as animal studies, are not within the scope of the journal.
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