Maria Del Mar García Ródenas, Luis Manuel Hernández Blasco, Francisco Javier Fernández Sánchez, Francisco Manuel Marco de la Calle, Jose-Francisco Pascual-Lledó, Ángel Sánchez Barbie, Cleofé Fernández Aracil
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The aim of this study was to evaluate the utility of basophil reactivity, measured through the basophil activation test (BAT), as a marker of response to mAbs.</p><p><strong>Methods: </strong>We measured basophil reactivity, using anti-immunoglobulin E (anti-IgE) antibodies as a stimulus, in 72 consecutive patients with severe uncontrolled asthma before initiation of treatment with mAbs. Forty-nine patients received omalizumab, 28 received mepolizumab, and 23 received benralizumab at some point. The Spanish Asthma Management Guidelines (GEMA) informed clinical management throughout the study. We studied clinical characteristics, laboratory values, and measures of respiratory function and asthma control.</p><p><strong>Results: </strong>Basophil reactivity (at the highest anti-IgE dilution at which basophil activation was positive) was inversely associated with asthma control and response to any mAb. The patients with higher basophil reactivity (≥ 29% versus < 29%) had lower mAb complete response, more frequent mAb switches, and worse baseline lung function and Asthma Control Test (ACT) scores. 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引用次数: 0
摘要
自单克隆抗体(mab)问世以来,哮喘的预后有了显著改善。然而,尚无可靠的反应预测指标来帮助临床医生在临床实践指南中推荐的多种生物制剂中选择一种。本研究的目的是评估通过嗜碱性粒细胞活化试验(BAT)测量的嗜碱性粒细胞反应性作为对单克隆抗体反应的标志的效用。方法:我们使用抗免疫球蛋白E(抗ige)抗体作为刺激,在开始单克隆抗体治疗前连续测量72例严重不受控制的哮喘患者的嗜碱性粒细胞反应性。49例患者接受了omalizumab, 28例接受了mepolizumab, 23例接受了benralizumab。在整个研究过程中,西班牙哮喘管理指南(GEMA)告知了临床管理。我们研究了临床特征、实验室值、呼吸功能和哮喘控制措施。结果:嗜碱性粒细胞反应性(在抗ige浓度最高时,嗜碱性粒细胞激活呈阳性)与哮喘控制和对任何单抗的反应呈负相关。嗜碱性粒细胞反应性较高(≥29% vs < 29%)的患者单克隆抗体完全缓解较低,单克隆抗体切换更频繁,基线肺功能和哮喘控制测试(ACT)评分较差。BAT与mepolizumab的10.5%、omalizumab的15.5%和benralizumab的28%的临界值以上的不良反应相关。结论:嗜碱性粒细胞反应性大于或等于29%的患者在接受omalizumab、mepolizumab或benralizumab治疗时,独立于2型哮喘的经典临床或生物学标志物,实现哮喘完全控制的可能性较小。
Utility of the Basophil Reactivity Test in the Clinical Management of People with Severe Uncontrolled Asthma.
Introduction: The prognosis of asthma has improved significantly since the availability of monoclonal antibodies (mAbs). However, there are no robust predictive markers of response to help clinicians select one of the multiple biologicals recommended in clinical practice guidelines. The aim of this study was to evaluate the utility of basophil reactivity, measured through the basophil activation test (BAT), as a marker of response to mAbs.
Methods: We measured basophil reactivity, using anti-immunoglobulin E (anti-IgE) antibodies as a stimulus, in 72 consecutive patients with severe uncontrolled asthma before initiation of treatment with mAbs. Forty-nine patients received omalizumab, 28 received mepolizumab, and 23 received benralizumab at some point. The Spanish Asthma Management Guidelines (GEMA) informed clinical management throughout the study. We studied clinical characteristics, laboratory values, and measures of respiratory function and asthma control.
Results: Basophil reactivity (at the highest anti-IgE dilution at which basophil activation was positive) was inversely associated with asthma control and response to any mAb. The patients with higher basophil reactivity (≥ 29% versus < 29%) had lower mAb complete response, more frequent mAb switches, and worse baseline lung function and Asthma Control Test (ACT) scores. The BAT was associated with poor response above the cut-off values of 10.5% for mepolizumab, 15.5% for omalizumab, and 28% for benralizumab.
Conclusion: Patients with basophil reactivity greater than or equal to 29% were less likely to achieve full control of asthma when treated with omalizumab, mepolizumab, or benralizumab, independently of classic clinical or biological markers of type 2 asthma.
期刊介绍:
An international, peer-reviewed journal publishing original research, reports, editorials and commentaries on the following topics: Asthma; Pulmonary physiology; Asthma related clinical health; Clinical immunology and the immunological basis of disease; Pharmacological interventions and new therapies.
Although the main focus of the journal will be to publish research and clinical results in humans, preclinical, animal and in vitro studies will be published where they shed light on disease processes and potential new therapies.