Benralizumab in severe eosinophilic asthma in real life: confirmed effectiveness and contrasted effect on sputum eosinophilia versus exhaled nitric oxide fraction - PROMISE.
[en] BACKGROUND: Randomised controlled trials have shown that benralizumab, an anti-interleukin-5 receptor monoclonal antibody, reduces exacerbations and oral corticosteroid dose and improves asthma control and lung function in severe eosinophilic asthma. The aim of this study was to confirm results of randomised controlled trials in real life in a population of 73 patients with severe eosinophilic asthma treated with benralizumab for at least 12 months. METHODS: Patients underwent careful monitoring of asthma exacerbations, exhaled nitric oxide fraction, lung function, asthma control and quality of life questionnaire responses and sputum induction, and gave a blood sample at baseline, after 6 months and then every year. RESULTS: We found significant reductions in exacerbations (by 92%, p<0.0001) and oral corticosteroid dose (by 83%, p<0.001) after 6 months that were maintained over time, with 78% of patients able to stop oral corticosteroid therapy. Patients improved their Asthma Control Test (ACT) score (from 11.7±5.1 to 16.9±5.35, p<0.0001), Asthma Control Questionnaire (ACQ) score (from 2.88±1.26 to 1.77±1.32, p<0.0001) and Asthma Quality of Life Questionnaire score (+1.04, p<0.0001) at 6 months and this was maintained during follow-up. Only 35% and 43% of patients reached asthma control according to an ACT score ≥20 and ACQ score <1.5, respectively. We observed stable post-bronchodilation lung function over time and a significant reduction in sputum eosinophil count, with 85% of patients exhibiting sputum eosinophil counts <3% after 6 months (p<0.01) with no effect on exhaled nitric oxide fraction. CONCLUSION: In our real-life study, we confirm the results published in randomised controlled trials showing a sharp reduction in exacerbations and oral corticosteroid therapy, an improvement in asthma control and quality of life, and a dramatic reduction in sputum eosinophil count.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Schleich, FLorence ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Moermans, Catherine ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Seidel, Laurence ; Centre Hospitalier Universitaire de Liège - CHU > > Service des informations médico économiques (SIME)
Kempeneers, Céline ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie
Louis, Gilles ; Université de Liège - ULiège > Santé publique : de la Biostatistique à la Promotion de la Santé
ROGISTER, Florence ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'ORL, d'audiophonologie et de chir. cervico-faciale
Tombu, Sophie ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'ORL, d'audiophonologie et de chir. cervico-faciale
Pottier, Laurence ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'ORL, d'audiophonologie et de chir. cervico-faciale
Poirrier, Anne-Lise ; Centre Hospitalier Universitaire de Liège - CHU > > Service d'ORL, d'audiophonologie et de chir. cervico-faciale
ZIANT, Stéphanie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Henket, Monique ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
SANCHEZ, Carole ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
PAULUS, Virginie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
GUISSARD, Françoise ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Donneau, Anne-Françoise ; Université de Liège - ULiège > Département des sciences de la santé publique
Louis, Renaud ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pneumologie - allergologie
Benralizumab in severe eosinophilic asthma in real life: confirmed effectiveness and contrasted effect on sputum eosinophilia versus exhaled nitric oxide fraction - PROMISE.
Schleich FN, Chevremont A, Paulus V, et al. Importance of concomitant local and systemic eosinophilia in uncontrolled asthma. Eur Respir J 2014; 44: 97–108.
Schleich F, Brusselle G, Louis R, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir Med 2014; 108: 1723–1732.
Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014; 43: 343–373.
Schleich F, Bougard N, Moermans C, et al. Cytokine-targeted therapies for asthma and COPD. Eur Respir Rev 2023; 32: 220193.
Rådinger M, Lötvall J. Eosinophil progenitors in allergy and asthma – do they matter? Pharmacol Ther 2009; 121: 174–184.
Graff S, Bricmont N, Moermans C, et al. Clinical and biological factors associated with irreversible airway obstruction in adult asthma. Respir Med 2020; 175: 106202.
Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016; 388: 2115–2127.
FitzGerald JM, Bleecker ER, Nair P, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2016; 388: 2128–2141.
Nair P, Wenzel S, Rabe KF, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med 2017; 376: 2448–2458.
Menzies-Gow A, Gurnell M, Heaney LG, et al. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. Lancet Respir Med 2022; 10: 47–58.
Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention. 2018. Available from: http://ginasthma.org/
Juniper EF, Guyatt GH, Epstein RS, et al. Evaluation of impairment of health-related quality of life in asthma: development of a questionnaire for use in clinical trials. Thorax 1992; 47: 76–83.
Juniper EF, O’Byrne PM, Guyatt GH, et al. Development and validation of a questionnaire to measure asthma control. Eur Respir J 1999; 14: 902–907.
Nathan RA, Sorkness CA, Kosinski M, et al. Development of the Asthma Control Test: a survey for assessing asthma control. J Allergy Clin Immunol 2004; 113: 59–65.
Delvaux M, Henket M, Lau L, et al. Nebulised salbutamol administered during sputum induction improves bronchoprotection in patients with asthma. Thorax 2004; 59: 111–115.
Harrison TW, Chanez P, Menzella F, et al. 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. Lancet Respir Med 2021; 9: 260–274.
Thomson NC, Chaudhuri R, Livingston E. Asthma and cigarette smoking. Eur Respir J 2004; 24: 822–833.
Klein DK, Silberbrandt A, Frøssing L, et al. Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma. Eur Respir J 2022; 60: 2102446.
Menzella F, Bargagli E, Aliani M, et al. ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving benralizumab in a real-life setting: the observational rEtrospective ANANKE study. Respir Res 2022; 23: 36.
Kavanagh JE, Hearn AP, Dhariwal J, et al. Real-world effectiveness of benralizumab in severe eosinophilic asthma. Chest 2021; 159: 496–506.
Padilla-Galo A, Levy-Abitbol RC, Olveira C, et al. Real-life experience with benralizumab during 6 months. BMC Pulm Med 2020; 20: 184.
Vitale C, Maglio A, Pelaia C, et al. Effectiveness of benralizumab in OCS-dependent severe asthma: the impact of 2 years of therapy in a real-life setting. J Clin Med 2023; 12: 985.
Louis R, Harrison TW, Chanez P, et al. Severe asthma standard-of-care background medication reduction with benralizumab: ANDHI in practice substudy. J Allergy Clin Immunol Pract 2023; 11: 1759–1770.
d’Ancona G, Kavanagh JE, Dhariwal J, et al. Adherence to inhaled corticosteroids and clinical outcomes following a year of benralizumab therapy for severe eosinophilic asthma. Allergy 2021; 76: 2238–2241.
Schleich F, Graff S, Nekoee H, et al. Real-world experience with mepolizumab: does it deliver what it has promised? Clin Exp Allergy 2020; 50: 687–695.
Graff S, Brusselle G, Hanon S, et al. Anti-interleukin-5 therapy is associated with attenuated lung function decline in severe eosinophilic asthma patients from the Belgian Severe Asthma Registry. J Allergy Clin Immunol Pract 2022; 10: 467–477.
McDowell PJ, Diver S, Yang F, et al. The inflammatory profile of exacerbations in patients with severe refractory eosinophilic asthma receiving mepolizumab (the MEX study): a prospective observational study. Lancet Respir Med 2021; 9: 1174–1184.
Schleich FN, Seidel L, Sele J, et al. Exhaled nitric oxide thresholds associated with a sputum eosinophil count ⩾3% in a cohort of unselected patients with asthma. Thorax 2010; 65: 1039–1044.
Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009; 360: 973–984.
Moermans C, Brion C, Bock G, et al. Sputum type 2 markers could predict remission in severe asthma treated with anti-IL-5. Chest 2023; 163: 1368–1379.
Weinstein SF, Katial RK, Bardin P, et al. Effects of reslizumab on asthma outcomes in a subgroup of eosinophilic asthma patients with self-reported chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract 2019; 7: 589–596.
