Pharmacokinetics/pharmacodynamics of benralizumab in chronic rhinosinusitis with nasal polyps: Phase III, randomized, placebo-controlled OSTRO trial.
basophils
benralizumab
chronic rhinosinusitis with nasal polyps
eosinophils
interleukin‐5
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
07 May 2024
07 May 2024
Historique:
revised:
27
03
2024
received:
24
07
2023
accepted:
04
04
2024
medline:
8
5
2024
pubmed:
8
5
2024
entrez:
8
5
2024
Statut:
aheadofprint
Résumé
Benralizumab, a humanized, afucosylated monoclonal antibody against the interleukin 5 receptor, α subunit, causes rapid depletion of eosinophils by antibody-dependent cellular cytotoxicity. We investigated the pharmacokinetic and pharmacodynamic effects of benralizumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) from the phase III OSTRO trial. Patients received a placebo or 30 mg of benralizumab by subcutaneous injection every 8 weeks (first three doses every 4 weeks) to week 48; a subset of patients continued in an extended follow-up period to assess treatment durability to week 80. Serum benralizumab concentrations and blood eosinophil and basophil counts were assessed to week 80. Biomarker assessments were performed on nasal polyp tissue biopsies at week 56 and nasal lining fluid at weeks 24 and 56 to examine changes in immune cells and inflammatory mediators. Among 185 patients in this analysis, 93 received benralizumab. Serum benralizumab concentrations reached a steady state by week 24 (median concentration 385.52 ng mL Benralizumab treatment led to rapid, sustained, nearly complete depletion of eosinophils from blood and nasal polyp tissue in patients with CRSwNP.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : AstraZeneca
Informations de copyright
© 2024 AstraZeneca. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Références
Schleimer RP. Immunopathogenesis of chronic rhinosinusitis and nasal polyposis. Annu Rev Pathol. 2017;12(1):331‐357. doi:10.1146/annurev‐pathol‐052016‐100401
Stevens WW, Schleimer RP, Kern RC. Chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2016;4(4):565‐572. doi:10.1016/j.jaip.2016.04.012
Brown WC, Senior B. A critical look at the efficacy and costs of biologic therapy for chronic rhinosinusitis with nasal polyposis. Curr Allergy Asthma Rep. 2020;20(6):16. doi:10.1007/s11882‐020‐00910‐y
Vlaminck S, Vauterin T, Hellings PW, et al. The importance of local eosinophilia in the surgical outcome of chronic rhinosinusitis: a 3‐year prospective observational study. Am J Rhinol Allergy. 2014;28(3):260‐264. doi:10.2500/ajra.2014.28.4024
Tajudeen BA, Ganti A, Kuhar HN, et al. The presence of eosinophil aggregates correlates with increased postoperative prednisone requirement. Laryngoscope. 2019;129(4):794‐799. doi:10.1002/lary.27693
Bachert C, Bhattacharyya N, Desrosiers M, Khan AH. Burden of disease in chronic rhinosinusitis with nasal polyps. J Asthma Allergy. 2021;14:127‐134. doi:10.2147/JAA.S290424
Milonski J, Zielinska‐Blizniewska H, Majsterek I, et al. Expression of POSTN, IL‐4, and IL‐13 in chronic rhinosinusitis with nasal polyps. DNA Cell Biol. 2015;34(5):342‐349. doi:10.1089/dna.2014.2712
Agache I, Song Y, Alonso‐Coello P, et al. Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: a systematic review for the EAACI guidelines. Allergy. 2021;76(8):2337‐2353. doi:10.1111/all.14809
Laidlaw TM, Prussin C, Panettieri RA, et al. Dexpramipexole depletes blood and tissue eosinophils in nasal polyps with no change in polyp size. Laryngoscope. 2019;129(2):E61‐E66. doi:10.1002/lary.27564
Mahdavinia M, Carter RG, Ocampo CJ, et al. Basophils are elevated in nasal polyps of patients with chronic rhinosinusitis without aspirin sensitivity. J Allergy Clin Immunol. 2014;133(6):1759‐1763. doi:10.1016/j.jaci.2013.12.1092
Takabayashi T, Kato A, Peters AT, et al. Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2012;130(2):e415. doi:10.1016/j.jaci.2012.02.046
Wang X, Zhang N, Bo M, et al. Diversity of T(H) cytokine profiles in patients with chronic rhinosinusitis: a multicenter study in Europe, Asia, and Oceania. J Allergy Clin Immunol. 2016;138(5):1344‐1353. doi:10.1016/j.jaci.2016.05.041
Baba S, Kagoya R, Kondo K, Suzukawa M, Ohta K, Yamasoba T. T‐cell phenotypes in chronic rhinosinusitis with nasal polyps in Japanese patients. Allergy Asthma Clin Immunol. 2015;11(1):33. doi:10.1186/s13223‐015‐0100‐2
Noyama Y, Okano M, Fujiwara T, et al. IL‐22/IL‐22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression. Allergol Int. 2017;66(1):42‐51. doi:10.1016/j.alit.2016.04.017
Calus L, Van Bruaene N, Bosteels C, et al. Twelve‐year follow‐up study after endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyposis. Clin Transl Allergy. 2019;9(1):30. doi:10.1186/s13601‐019‐0269‐4
Chen S, Zhou A, Emmanuel B, Thomas K, Guiang H. Systematic literature review of the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyposis. Curr Med Res Opin. 2020;36(11):1897‐1911. doi:10.1080/03007995.2020.1815682
Al‐Ahmad M, Alsaleh S, Al‐Reefy H, et al. Expert opinion on biological treatment of chronic rhinosinusitis with nasal polyps in the Gulf region. J Asthma Allergy. 2022;15:1‐12. doi:10.2147/JAA.S321017
Hellings PW, Verhoeven E, Fokkens WJ. State‐of‐the‐art overview on biological treatment for CRSwNP. Rhinology. 2021;59(2):151‐163. doi:10.4193/Rhin20.570
Kolbeck R, Kozhich A, Koike M, et al. MEDI‐563, a humanized anti‐IL‐5 receptor alpha mAb with enhanced antibody‐dependent cell‐mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125(6):e1342. doi:10.1016/j.jaci.2010.04.004
Pham TH, Damera G, Newbold P, Ranade K. Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21‐29. doi:10.1016/j.rmed.2016.01.003
Agache I, Beltran J, Akdis C, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI guidelines ‐ recommendations on the use of biologicals in severe asthma. Allergy. 2020;75(5):1023‐1042. doi:10.1111/all.14221
Bachert C, Han JK, Desrosiers MY, et al. Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: a randomized, placebo‐controlled trial. J Allergy Clin Immunol. 2022;149(4):e1312. doi:10.1016/j.jaci.2021.08.030
Alexander SP, Kelly E, Mathie A, et al. The Concise Guide to Pharmacology 2021/22: introduction and other protein targets. Br J Pharmacol. 2021;178(Suppl 1):S1‐S26. doi:10.1111/bph.15537
Wang B, Yan L, Yao Z, Roskos LK. Population pharmacokinetics and pharmacodynamics of benralizumab in healthy volunteers and patients with asthma. CPT Pharmacometrics Syst Pharmacol. 2017;6(4):249‐257. doi:10.1002/psp4.12160
Pelaia C, Busceti MT, Vatrella A, et al. Real‐life rapidity of benralizumab effects in patients with severe allergic eosinophilic asthma: assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after the first drug dose. Pulm Pharmacol Ther. 2019;58:101830. doi:10.1016/j.pupt.2019.101830
Laviolette M, Gossage DL, Gauvreau G, et al. Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013;132(5):e1085. doi:10.1016/j.jaci.2013.05.020
Koike M, Nakamura K, Furuya A, et al. Establishment of humanized anti‐interleukin‐5 receptor alpha chain monoclonal antibodies having a potent neutralizing activity. Hum Antibodies. 2009;18(1‐2):17‐27. doi:10.3233/HAB‐2009‐0198
Izumo T, Tone M, Kuse N, et al. Effectiveness and safety of benralizumab for severe asthma in clinical practice (J‐BEST): a prospective study. Ann Transl Med. 2020;8(7):438. doi:10.21037/atm.2020.04.01
Pelaia C, Crimi C, Benfante A, et al. Therapeutic effects of benralizumab assessed in patients with severe eosinophilic asthma: real‐life evaluation correlated with allergic and non‐allergic phenotype expression. J Asthma Allergy. 2021;14:163‐173. doi:10.2147/JAA.S297273
Lommatzsch M, Marchewski H, Schwefel G, Stoll P, Virchow JC, Bratke K. Benralizumab strongly reduces blood basophils in severe eosinophilic asthma. Clin Exp Allergy. 2020;50(11):1267‐1269. doi:10.1111/cea.13720
Nolasco S, Crimi C, Pelaia C, et al. Benralizumab effectiveness in severe eosinophilic asthma with and without chronic rhinosinusitis with nasal polyps: a real‐world multicenter study. J Allergy Clin Immunol Pract. 2021;9(12):e4374. doi:10.1016/j.jaip.2021.08.004
Guillet C, Steinmann S, Lang C, Maul JT, Schmid‐Grendelmeier P. Eosinophil‐mast cell interaction: mepolizumab leads to a reduction of clinical symptoms and serum tryptase in a patient with eosinophilic asthma and idiopathic mast cell activation. J Allergy Clin Immunol Pract. 2021;9(3):e1391. doi:10.1016/j.jaip.2020.10.020
Otani IM, Anilkumar AA, Newbury RO, et al. Anti‐IL‐5 therapy reduces mast cell and IL‐9 cell numbers in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol. 2013;131(6):1576‐1582. doi:10.1016/j.jaci.2013.02.042
Sridhar S, Liu H, Pham TH, Damera G, Newbold P. Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases. Respir Res. 2019;20(1):14. doi:10.1186/s12931‐018‐0968‐8
Bachert C, Desrosiers MY, Hellings PW, Laidlaw TM. The role of biologics in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2021;9(3):1099‐1106. doi:10.1016/j.jaip.2020.11.017
Gevaert P, Han JK, Smith SG, et al. The roles of eosinophils and interleukin‐5 in the pathophysiology of chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol. 2022;12(11):1413‐1423. doi:10.1002/alr.22994
Han JK, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet Respir Med. 2021;9(10):1141‐1153. doi:10.1016/S2213‐2600(21)00097‐7
Tomassen P, Vandeplas G, Van Zele T, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016;137(5):e1444. doi:10.1016/j.jaci.2015.12.1324
Bachert C, Zhang N, Cavaliere C, Weiping W, Gevaert E, Krysko O. Biologics for chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2020;145(3):725‐739. doi:10.1016/j.jaci.2020.01.020
Bachert C, Gevaert P, Hellings P. Biotherapeutics in chronic rhinosinusitis with and without nasal polyps. J Allergy Clin Immunol Pract. 2017;5(6):1512‐1516. doi:10.1016/j.jaip.2017.04.024
Laidlaw TM, Buchheit KM. Biologics in chronic rhinosinusitis with nasal polyposis. Ann Allergy Asthma Immunol. 2020;124(4):326‐332. doi:10.1016/j.anai.2019.12.001
Kliewer KL, Murray‐Petzold C, Collins MH, et al. Benralizumab for eosinophilic gastritis: a single‐site, randomised, double‐blind, placebo‐controlled, phase 2 trial. Lancet Gastroenterol Hepatol. 2023;8(9):803‐815. doi:10.1016/S2468‐1253(23)00145‐0
Barretto KT, Brockman‐Schneider RA, Kuipers I, et al. Human airway epithelial cells express a functional IL‐5 receptor. Allergy. 2020;75(8):2127‐2130. doi:10.1111/all.14297