Onset of effect and impact on health-related quality of life, exacerbation rate, lung function, and nasal polyposis symptoms for patients with severe eosinophilic asthma treated with benralizumab (ANDHI): a randomised, controlled, phase 3b trial

Eosinophils as Drivers of Severe Eosinophilic Asthma: Endotypes or Plasticity?

“…Further post-hoc stratification of the response of SEA patients according to other disease phenotypic traits failed to detect an effect of the atopic status, IgE serum concentrations, allergy to fungal antigens or house dust mites [ 74 , 76 , 77 , 78 , 79 ], or of body mass index [ 74 , 80 ]. A generally better response was, however, noted with benralizumab and reslizumab for patients with AOA compared with those with COA in terms of the reduction of exacerbations and improvement of FEV1 [ 28 , 29 , 30 ]. Interestingly, this better response of adult-onset SEA patients still remained, or was even more prominent, when patients in the COA and AOA groups were first selected for blood eosinophil counts >300 cells/µL [ 29 , 30 ].…”

“…A generally better response was, however, noted with benralizumab and reslizumab for patients with AOA compared with those with COA in terms of the reduction of exacerbations and improvement of FEV1 [ 28 , 29 , 30 ]. Interestingly, this better response of adult-onset SEA patients still remained, or was even more prominent, when patients in the COA and AOA groups were first selected for blood eosinophil counts >300 cells/µL [ 29 , 30 ]. A similar trend was observed in a post hoc analysis of the SIROCCO and CALIMA randomized control trials when focusing on patients with blood eosinophil counts >300 cells/µL and stratified based on the presence or absence of fixed airway obstruction (FAO) [ 69 ].…”

“…Nonetheless, anti-eosinophil biological treatments mostly provide clear benefits specifically in SEA, but not in non-T2 asthma [ 27 ], indicating that eosinophils are not systematically important drivers of asthma symptoms. In addition, recent analyses suggest that anti-eosinophil therapeutics on average provide more marked benefits in terms of reduction in exacerbation rates and improvement of lung function in SEA patients with AOA compared with COA [ 28 , 29 , 30 ]. Clinical findings with anti-eosinophil therapeutics thereby suggest that eosinophils, even when infiltrating the lungs in significant numbers, may have a variable impact on asthma manifestations, depending on the disease phenotype or endotype.…”

Molecular Targets for Biological Therapies of Severe Asthma: Focus on Benralizumab and Tezepelumab

“…Benralizumab treatment enabled patients with severe, uncontrolled OCS-dependent asthma and baseline blood eosinophil counts ≥150 cells/uL to achieve and maintain asthma control while reducing OCS dosages [ 10 ]. The ANDHI study increases confidence in the benralizumab mechanism of action for treating patients with severe eosinophilic asthma through further assessment of the onset and maintenance of clinical effects, benefits in health-related quality of life (HRQOL) measures, and the potential to treat symptoms of nasal polyposis for patients with chronic rhinosinusitis with nasal polyposis [ 11 ]. Treatment with benralizumab for patients with severe eosinophilic asthma (BEC ≥ 150 cells per μL) significantly reduced the risk of asthma exacerbation, which was primarily driven by patients with efficacy associated with known markers of the eosinophilic phenotype.…”

“…Systemic reviews have been carried out for severe asthma in omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab from 2017 to 2021 [ 3 , 16 , 17 , 18 , 19 ]; however, only one of them has been reviewed in both benralizumab and tezepelumab [ 19 ]. The study was conducted in 2020, which did not include phase 3 NAVIGATOR study for tezepelumab [ 20 ], or phase 3b ANDHI study for benralizumab [ 11 ]. An Italian cross-sectional study analyzed real-life descriptions of severe refractory population from June 2017 to June 2019 [ 21 ].…”