Joanne E Kavanagh1, Andrew P Hearn1, Jaideep Dhariwal2, Gráinne d'Ancona2, Abdel Douiri3, Cris Roxas2, Mariana Fernandes2, Linda Green2, Louise Thomson2, Alexandra M Nanzer2, Brian D Kent4, David J Jackson5. 1. Guy's Severe Asthma Centre, Guy's and St Thomas' Hospitals, London, England; Asthma UK Centre, King's College London, London, England. 2. Guy's Severe Asthma Centre, Guy's and St Thomas' Hospitals, London, England. 3. Department of Medical Statistics, King's College London, London, England. 4. Department of Respiratory Medicine, St. James' Hospital, Dublin, Ireland; School of Medicine, Trinity College, Dublin, Ireland. 5. Guy's Severe Asthma Centre, Guy's and St Thomas' Hospitals, London, England; Asthma UK Centre, King's College London, London, England. Electronic address: David.jackson@gstt.nhs.uk.
Abstract
BACKGROUND: Benralizumab is an IL5-receptor monoclonal antibody licensed for the treatment of severe eosinophilic asthma (SEA). It has demonstrated efficacy in clinical trials in reducing asthma exacerbation rates and maintenance oral corticosteroids (mOCSs). RESEARCH QUESTION: What is the real-world effectiveness of benralizumab and what baseline characteristics are associated with response to therapy? STUDY DESIGN AND METHODS: We assessed outcomes in all SEA patients who began benralizumab treatment at our specialist center. At each dosing visit, exacerbation history, mOCS dose, spirometry, and Asthma Control Questionnaire (ACQ6) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) scores were recorded. Response to treatment was defined as a reduction of ≥ 50% in annualized exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super response was defined as zero exacerbations and no mOCSs for asthma. RESULTS: One hundred thirty patients were included in the analysis. At 48 weeks, a 72.8% reduction in AER was noted, from 4.92 ± 3.35 per year in the year preceding biologic treatment to 1.34 ± 1.71 per year (P < .001), including 57 patients (43.8%) who were exacerbation-free with benralizumab. In those receiving mOCSs (n = 74 [56.9%]), the median daily prednisolone dose fell from 10 mg (interquartile range, 5-20 mg) to 0 mg (interquartile range, 0-5 mg; P < .001), and 38 of 74 patients (51.4%) were able to discontinue mOCS therapy. Clinically and statistically significant improvements were found in ACQ6 scores, mAQLQ scores, and FEV1. Overall, 51 patients (39%) met the super responder definition and 112 patients (86%) met the responder definition. The optimal regression model of super responders vs other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen patients (13.8%) were nonresponders to benralizumab. Evidence of chronic airway infection was observed in 6 of 18 patients, and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies was observed in 5 of 18 patients. INTERPRETATION: In a large real-world SEA cohort, benralizumab led to significant improvements in all clinical outcome measures. A lack of response was seen in a minority of patients and should be a focus for future investigation.
BACKGROUND:Benralizumab is an IL5-receptor monoclonal antibody licensed for the treatment of severe eosinophilic asthma (SEA). It has demonstrated efficacy in clinical trials in reducing asthma exacerbation rates and maintenance oral corticosteroids (mOCSs). RESEARCH QUESTION: What is the real-world effectiveness of benralizumab and what baseline characteristics are associated with response to therapy? STUDY DESIGN AND METHODS: We assessed outcomes in all SEA patients who began benralizumab treatment at our specialist center. At each dosing visit, exacerbation history, mOCS dose, spirometry, and Asthma Control Questionnaire (ACQ6) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) scores were recorded. Response to treatment was defined as a reduction of ≥ 50% in annualized exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super response was defined as zero exacerbations and no mOCSs for asthma. RESULTS: One hundred thirty patients were included in the analysis. At 48 weeks, a 72.8% reduction in AER was noted, from 4.92 ± 3.35 per year in the year preceding biologic treatment to 1.34 ± 1.71 per year (P < .001), including 57 patients (43.8%) who were exacerbation-free with benralizumab. In those receiving mOCSs (n = 74 [56.9%]), the median daily prednisolone dose fell from 10 mg (interquartile range, 5-20 mg) to 0 mg (interquartile range, 0-5 mg; P < .001), and 38 of 74 patients (51.4%) were able to discontinue mOCS therapy. Clinically and statistically significant improvements were found in ACQ6 scores, mAQLQ scores, and FEV1. Overall, 51 patients (39%) met the super responder definition and 112 patients (86%) met the responder definition. The optimal regression model of super responders vs other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen patients (13.8%) were nonresponders to benralizumab. Evidence of chronic airway infection was observed in 6 of 18 patients, and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies was observed in 5 of 18 patients. INTERPRETATION: In a large real-world SEA cohort, benralizumab led to significant improvements in all clinical outcome measures. A lack of response was seen in a minority of patients and should be a focus for future investigation.
Authors: Jaideep Dhariwal; Aoife Cameron; Ernie Wong; Malte Paulsen; Maria-Belen Trujillo-Torralbo; Ajerico Del Rosario; Eteri Bakhsoliani; Tatiana Kebadze; Mark Almond; Hugo Farne; Leila Gogsadze; Julia Aniscenko; Batika M J Rana; Trevor T Hansel; David J Jackson; Onn Min Kon; Michael R Edwards; Roberto Solari; David J Cousins; Ross P Walton; Sebastian L Johnston Journal: Am J Respir Crit Care Med Date: 2021-12-01 Impact factor: 30.528
Authors: Elizabeth A Jacobsen; David J Jackson; Enrico Heffler; Sameer K Mathur; Albert J Bredenoord; Ian D Pavord; Praveen Akuthota; Florence Roufosse; Marc E Rothenberg Journal: Annu Rev Immunol Date: 2021-03-01 Impact factor: 28.527
Authors: A Padilla-Galo; A J García-Ruiz; R Ch Levy Abitbol; C Olveira; F Rivas-Ruiz; N García-Agua Soler; M Pérez Morales; B Valencia Azcona; B Tortajada-Goitia; I Moya-Carmona; A Levy-Naon Journal: Respir Res Date: 2021-05-27