Utility of the Basophil Reactivity Test in the Clinical Management of People with Severe Uncontrolled Asthma

Maria del Mar García Ródenas,1 Luis Manuel Hernández Blasco,2 Francisco Javier Fernández Sánchez,3 Francisco Manuel Marco de la Calle,4 Jose-Francisco Pascual-Lledó,1 Ángel Sánchez Barbie,5 Cleofé Fernández Aracil2 1Department of Pulmonology, Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain; 2Department of Pulmonology, Dr. Balmis General University Hospital. Clinical Medicine Department, Miguel Hernandez University; Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain; 3Department of Allergology, Dr. Balmis General University Hospital; Miguel Hernández University; Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain; 4Department of Immunology, Dr. Balmis General University Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain; 5Department of Statistics, Mathematics and Computer Science of Miguel Hernández University, Alicante, SpainCorrespondence: Maria del Mar García Ródenas, Email [email protected]: 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.Keywords: basophil activation test, asthma, monoclonal antibodies, omalizumab, mepolizumab, benralizumab