Effects of benralizumab in a population of patients affected by severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: a real life study
Main Article Content
nasal cytology, eosinophils, severe asthma, nasal polyposis, benralizumab
Background. Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent comorbidity in severe eosinophilic asthma (SEA), which may contribute to the loss of asthma control. CRSwNP and SEA share a T2-mediated mechanism and the use of some anti-asthma monoclonal antibodies has recently been extended to CRSwNP. Unlike dupilumab and omalizumab, benralizumab approval for CRSwNP is ongoing. We aimed to evaluate the efficacy of benralizumab efficacy on SEA and on CRSwNP in patients affected by both pathologies in a real life setting.
Methods. 17 patients affected by both SEA and CRSwNP participated to our study. At baseline (T0) and at one year after benralizumab initiation (T1), all participants underwent spirometry, exhaled nitric oxide (FeNO), Asthma Control Test (ACT), nasal endoscopy with Nasal Polyp Score (NPS), nasal cytology and Sino-Nasal Outcome Test 22 (SNOT 22).The continuous oral corticosteroid therapy (OCS), the number of year exacerbations and the need for sinus surgery were also evaluated for each patient.
Results. At T1, a marked reduction of SNOT-22, NPS, nasal eosinophils and neutrophils count were shown compared to T0. Moreover, at T1 ACT was significantly increased and FeNO, exacerbations/year and mean OCS dosage were significantly reduced compared to T0.
Conclusions. Our real-life study demonstrates the efficacy of benralizumab not only on SEA but also on nasal cytology and on nasal polyposis, confirming that patients affected by both SEA and CRSwNP may receive a considerable benefit from anti-IL5 receptor, treating both the comorbidities at once.
2. Gershon AS, Guan J, Wang C et al. Describing and quantifying asthma comorbidity: a population study. 2012. PLoS One, 7.
3. Ekström M, Nwaru BI, Hasvold P et al. Oral corticosteroid use, morbidity and mortality in asthma: A nationwide prospective cohort study in Sweden. Allergy 2019;74:2181-2190.
4. Seybt MW,McMains KC, Kountakis SE. The prevalence and effect of asthma on adults with chronic rhinosinusitis. Ear Nose Throat J 2007;86:409-411.
5. Okano M, Kariya S, Ohta N et al. Association and management of eosinophilic inflammation in upper and lower airways. Allergol Int 2015;64:131-138.
6. Cao PP, Zhang YN, Liao B et al. Increased local IgE production induced by common aeroallergens and phenotypic alteration of mast cells in Chinese eosinophilic, but not non-eosinophilic, chronic rhinosinusitis with nasal polyps. Clin Exp Allergy 2014;44:690-700.
7. Global Initiative for Asthma. Difficult to treat and severe asthma in adolescents and adult patients. Diagnosis and management. V 2.0 april 2019, available from www.ginasthma.org.
8. Lombardi C, Passalacqua G, Bagnasco D. Severe asthma, biologicals, and auto-injection: Yes, no, may be! Allergy 2019;75:444-5.
9. Buonamico E, Dragonieri D, Sciancalepore PI et al. Assessment of eosinophilic nasal inflammation in patients with severe asthma and nasal polyposis before and after six months of therapy with Benralizumab. J Biol Regul Homeost Agents.2020;34:2353-2357
10. Stanojevic S, Kaminsky DA, Miller M, et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J 2021.
11. American Thoracic S., European Respiratory S. ATS/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005. Am J Respir Crit Care Med 2005;171:912–930.
12. Lund VJ, Kennedy DW. Staging for rhinosinusitis. Otolaryngol Head Neck Surg1997;117:S35-S40.
13. Bogaerts P, Clement P. The diagnostic value of a cytogram in rhinopathology. Rhinology 1981;19:203-208.
14. Gelardi M, Fiorella ML, Leocao G et al. Cytology in the diagnosis of rhinosinusitis. Pediatr Allergy Immunol 2007:18;50-52.
15. Proimos E, Papadakis CE, Chimona TS et al. The effect of functional endoscopic sinus surgery on patients with asthma and CRS with nasal polyps. Rhinology 2010;48:331-8.
16. Gelardi M, Iannuzzi L, De Giosa M. Non-surgical management of chronic rhinosinusitis with nasal polyps based on clinical-cytological grading: a precision medicine-based approach. Acta Otorhinolaryngol Ital. 2017;37:38-45.
17. Matera MG, Calzetta L, Rinaldi B et al. Pharmacokinetic/pharmacodynamic drug evaluation of benralizumab for the treatment of asthma. Expert Opin Drug Metab Toxicol 2017;13:1007-1013.
18. 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 B2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 2016;388:2115-2127.
19. 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.
20. 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
21. Kavanagh JE, Hearn AP, Dhariwal J et al. Real-World Effectiveness of Benralizumab in Severe Eosinophilic Asthma. Chest 2021;159:496-506.
22. Watanabe H, Shirai T, Hirai K et al. Blood eosinophil count and FeNO to predict benralizumab effectiveness in real-life severe asthma patients. J Asthma 2021;17;1-9.
23. 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.
24. Takabayashi T, Asaka D, Okamoto Y et al. A Phase II, Multicenter, Randomized, Placebo-Controlled Study of Benralizumab, a Humanized Anti-IL-5R Alpha Monoclonal Antibody, in Patients With Eosinophilic Chronic Rhinosinusitis. Am J Rhinol Allergy 2021;35:861-870.
25. Bagnasco D, Brussino L, Bonavia M et al. Efficacy of Benralizumab in severe asthma in real life and focus on nasal polyposis. Respir Med 2020;171:106080.
26. 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;9:4371-4380.
27. Lombardo N, Pelaia C, Ciriolo M et al. Real-life effects of benralizumab on allergic chronic rhinosinusitis and nasal polyposis associated with severe asthma. Int J Immunopathol Pharmacol. 2020;34:2058738420950851.
28. Gevaert P, Bachert C, Holtappels G et al. Enhanced soluble interleukin-5 receptor alpha expression in nasal polyposis. Allergy 2003; 58: 371–379.
29. Lan F and Zhang L. Understanding the Role of Neutrophils in Refractoriness of Chronic Rhinosinusitis With Nasal Polyps. Allergy Asthma Immunol Res. 2020;12: 1–3.