Real World Effectiveness of Benralizumab in Severe Eosinophilic Asthma

TY - JOUR

T1 - Real World Effectiveness of Benralizumab in Severe Eosinophilic Asthma

AU - Kavanagh, Joanne E.

AU - Hearn, Andrew P.

AU - Dhariwal, Jaideep

AU - d'Ancona, Grainne

AU - Douiri, Abdel

AU - Roxas, Cris

AU - Fernandes, Mariana

AU - Green, Linda

AU - Thomson, Louise

AU - Nanzer, Alexandra M.

AU - Kent, Brian D.

AU - Jackson, David J.

N1 - Copyright © 2020. Published by Elsevier Inc.

PY - 2021/2

Y1 - 2021/2

N2 - 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 (mOCS).RESEARCH QUESTION: Our aim was to evaluate the real-world effectiveness of benralizumab and identify any baseline characteristics associated with response to therapy.STUDY DESIGN: & Methods: We assessed outcomes in all SEA patients commenced on benralizumab at our specialist centre. At each dosing visit, exacerbation history, mOCS dose, spirometry, 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 annualised exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super-response was defined as zero exacerbations and no mOCS for asthma.RESULTS: 130 patients were included in the analysis. At 48 weeks there was a 72.8% reduction in AER, from 4.92±3.35 in the year preceding biologic treatment to 1.34±1.71 (p<0.001), including 57(43.8%) patients who were exacerbation-free on benralizumab. In those on mOCS (n=74; 56.9%), the median daily prednisolone dose fell from 10mg (5-20) to 0mg (0-5) (p<0.001), and 38/74(51.4%) were able to discontinue mOCS. There were clinically and statistically significant improvements in ACQ6, mAQLQ and FEV1. Overall, 51 (39%) met the super-responder definition, and 112(86%) the responder definition. The optimal regression model of super-responders versus other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen (13.8%) patients were non-responders to benralizumab. Evidence of chronic airway infection was observed in 6/18 and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies in 5/18.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 and should be a focus for future investigation.

AB - 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 (mOCS).RESEARCH QUESTION: Our aim was to evaluate the real-world effectiveness of benralizumab and identify any baseline characteristics associated with response to therapy.STUDY DESIGN: & Methods: We assessed outcomes in all SEA patients commenced on benralizumab at our specialist centre. At each dosing visit, exacerbation history, mOCS dose, spirometry, 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 annualised exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super-response was defined as zero exacerbations and no mOCS for asthma.RESULTS: 130 patients were included in the analysis. At 48 weeks there was a 72.8% reduction in AER, from 4.92±3.35 in the year preceding biologic treatment to 1.34±1.71 (p<0.001), including 57(43.8%) patients who were exacerbation-free on benralizumab. In those on mOCS (n=74; 56.9%), the median daily prednisolone dose fell from 10mg (5-20) to 0mg (0-5) (p<0.001), and 38/74(51.4%) were able to discontinue mOCS. There were clinically and statistically significant improvements in ACQ6, mAQLQ and FEV1. Overall, 51 (39%) met the super-responder definition, and 112(86%) the responder definition. The optimal regression model of super-responders versus other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen (13.8%) patients were non-responders to benralizumab. Evidence of chronic airway infection was observed in 6/18 and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies in 5/18.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 and should be a focus for future investigation.

KW - benralizumab

KW - eosinophil

KW - real world

KW - response

KW - severe asthma

U2 - 10.1016/j.chest.2020.08.2083

DO - 10.1016/j.chest.2020.08.2083

M3 - Article

C2 - 32882249

SN - 0012-3692

VL - 159

SP - 496

EP - 506

JO - Chest

JF - Chest

IS - 2

ER -