Benralizumab for Allergic Asthma: a Randomised, Double-blind, Placebo-controlled Trial

Overview

Journal Eur Respir J

Specialty Pulmonary Medicine

Date 2024 Jul 26

PMID 39060015

Authors

Gail M Gauvreau

Roma Sehmi

J Mark FitzGerald

Richard Leigh

Donald W Cockcroft

Beth E Davis

Irvin Mayers

Louis-Philippe Boulet

Dhuha Al-Sajee

Brittany M Salter

Ruth P Cusack

Terence Ho

Christiane E Whetstone

Nadia Alsaji

Imran Satia

Kieran J Killian

Patrick D Mitchell

Iain P Magee

Celine Bergeron

Mohit Bhutani

Viktoria Werkstrom

Tomasz Durzynski

Kathryn Shoemaker

Rohit K Katial

Maria Jison

Paul Newbold

Christopher McCrae

Paul M OByrne

Affiliations

Soon will be listed here.

Abstract

Background: Benralizumab induces rapid and near-complete depletion of eosinophils from blood and lung tissue. We investigated whether benralizumab could attenuate the allergen-induced late asthmatic response (LAR) in participants with allergic asthma.

Methods: Participants with allergic asthma who demonstrated increased sputum eosinophils and LAR at screening were randomised to benralizumab 30 mg or matched placebo given every 4 weeks for 8 weeks (3 doses). Allergen challenges were performed at weeks 9 and 12 when blood, sputum, bone marrow and bronchial tissue eosinophils and LAR were assessed.

Results: 46 participants (mean age 30.9 years) were randomised to benralizumab (n=23) or placebo (n=23). Eosinophils were significantly reduced in the benralizumab group compared with placebo in blood at 4 weeks and sputum and bone marrow at 9 weeks after treatment initiation. At 7 h after an allergen challenge at week 9, sputum eosinophilia was significantly attenuated in the benralizumab group compared to placebo (least squares mean difference -5.81%, 95% CI -10.69- -0.94%; p=0.021); however, the LAR was not significantly different (least squares mean difference 2.54%, 95% CI 3.05-8.12%; p=0.363). Adverse events were reported for seven (30.4%) and 14 (60.9%) participants in the benralizumab and placebo groups, respectively.

Conclusion: Benralizumab administration over 8 weeks resulted in a significant attenuation of blood, bone marrow and sputum eosinophilia in participants with mild allergic asthma; however, there was no change in the LAR, suggesting that eosinophils alone are not a key component of allergen-induced bronchoconstriction.

References

Gauvreau G, Jordana M, Watson R, Cockroft D, OByrne P . Effect of regular inhaled albuterol on allergen-induced late responses and sputum eosinophils in asthmatic subjects. Am J Respir Crit Care Med. 1997; 156(6):1738-45. DOI: 10.1164/ajrccm.156.6.96-08042. View

Gauvreau G, Watson R, OByrne P . Kinetics of allergen-induced airway eosinophilic cytokine production and airway inflammation. Am J Respir Crit Care Med. 1999; 160(2):640-7. DOI: 10.1164/ajrccm.160.2.9809130. View

Sridhar S, Liu H, Pham T, Damera G, Newbold P . Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases. Respir Res. 2019; 20(1):14. PMC: 6339432. DOI: 10.1186/s12931-018-0968-8. View

Leckie M, Ten Brinke A, Khan J, Diamant Z, OConnor B, Walls C . Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2001; 356(9248):2144-8. DOI: 10.1016/s0140-6736(00)03496-6. View

FitzGerald J, Bleecker E, Nair P, Korn S, Ohta K, Lommatzsch M . 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(10056):2128-2141. DOI: 10.1016/S0140-6736(16)31322-8. View

Wright A, Weston C, Rana B, Brightling C, Cousins D . Human group 2 innate lymphoid cells do not express the IL-5 receptor. J Allergy Clin Immunol. 2017; 140(5):1430-1433.e4. PMC: 5667579. DOI: 10.1016/j.jaci.2017.04.025. View

Laviolette M, Gossage D, Gauvreau G, Leigh R, Olivenstein R, Katial R . Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013; 132(5):1086-1096.e5. PMC: 4172321. DOI: 10.1016/j.jaci.2013.05.020. View

Gauvreau G, El-Gammal A, OByrne P . Allergen-induced airway responses. Eur Respir J. 2015; 46(3):819-31. DOI: 10.1183/13993003.00536-2015. View

OByrne P, Inman M, Parameswaran K . The trials and tribulations of IL-5, eosinophils, and allergic asthma. J Allergy Clin Immunol. 2001; 108(4):503-8. DOI: 10.1067/mai.2001.119149. View

10.

Nair P, Wenzel S, Rabe K, Bourdin A, Lugogo N, Kuna P . Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017; 376(25):2448-2458. DOI: 10.1056/NEJMoa1703501. View

11.

Gauvreau G, OByrne P, Boulet L, Wang Y, Cockcroft D, Bigler J . Effects of an anti-TSLP antibody on allergen-induced asthmatic responses. N Engl J Med. 2014; 370(22):2102-10. DOI: 10.1056/NEJMoa1402895. View

12.

Mesnil C, Raulier S, Paulissen G, Xiao X, Birrell M, Pirottin D . Lung-resident eosinophils represent a distinct regulatory eosinophil subset. J Clin Invest. 2016; 126(9):3279-95. PMC: 5004964. DOI: 10.1172/JCI85664. View

13.

Inman M, Watson R, Rerecich T, Gauvreau G, Lutsky B, Stryszak P . Dose-dependent effects of inhaled mometasone furoate on airway function and inflammation after allergen inhalation challenge. Am J Respir Crit Care Med. 2001; 164(4):569-74. DOI: 10.1164/ajrccm.164.4.2007063. View

14.

Pakkasela J, Ilmarinen P, Honkamaki J, Tuomisto L, Andersen H, Piirila P . Age-specific incidence of allergic and non-allergic asthma. BMC Pulm Med. 2020; 20(1):9. PMC: 6954552. DOI: 10.1186/s12890-019-1040-2. View

15.

Percopo C, Brenner T, Ma M, Kraemer L, Hakeem R, Lee J . SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice. J Leukoc Biol. 2016; 101(1):321-328. PMC: 5166438. DOI: 10.1189/jlb.3A0416-166R. View

16.

Pham T, Damera G, Newbold P, Ranade K . Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016; 111:21-9. DOI: 10.1016/j.rmed.2016.01.003. View

17.

Pelikan Z . Expression of surface markers on the blood cells during the delayed asthmatic response to allergen challenge. Allergy Rhinol (Providence). 2014; 5(2):96-109. PMC: 4124585. DOI: 10.2500/ar.2014.5.0087. View

18.

Cockcroft D, Davis B, Boulet L, Deschesnes F, Gauvreau G, OByrne P . The links between allergen skin test sensitivity, airway responsiveness and airway response to allergen. Allergy. 2004; 60(1):56-9. DOI: 10.1111/j.1398-9995.2004.00612.x. View

19.

Kelly E, Esnault S, Liu L, Evans M, Johansson M, Mathur S . Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma. Am J Respir Crit Care Med. 2017; 196(11):1385-1395. PMC: 5736971. DOI: 10.1164/rccm.201611-2234OC. View

20.

Gauvreau G, Boulet L, Fitzgerald J, Cockcroft D, Davis B, Leigh R . A dual CysLT antagonist attenuates allergen-induced airway responses in subjects with mild allergic asthma. Allergy. 2016; 71(12):1721-1727. DOI: 10.1111/all.12987. View