İnsu YILMAZ, Murat TÜRK, Sakine Nazik BAHÇECİOĞLU, Nuri TUTAR, İnci GÜLMEZ

Efficacy of mepolizumab treatment in oral corticosteroid-dependent severe eosinophilic asthma patients with chronic rhinosinusitis with nasal polyps: single center, real life study

Background/aim: Oral corticosteroid OCS -dependent severe eosinophilic asthma with chronic rhinosinusitis with nasal polyps SEACRSwNP would be a suitable phenotype for mepolizumab treatment. This study evaluated the short-term efficacy of mepolizumab treatment in OCS-dependent SEA-CRSwNP. Materials and methods: Baseline and 24th week results [daily OCS doses, asthma exacerbation frequency, asthma control test ACT scores, blood eosinophil levels, FEV1 values, and numerical analog scale NAS of CRSwNP symptoms] of patients who were treated for at least 24 weeks with mepolizumab were retrospectively evaluated and compared. Results: A total of 16 patients were enrolled in the study. Mepolizumab was discontinued in one patient due to side effects. The daily OCS dosage was reduced from baseline in all patients, and at week 24 OCS was discontinued in 40% of the patients baseline mean steroid dose: 9.2 ± 5.2 mg, 24th week: 1.3 ± 1.4 mg; P

Keywords:

Severe asthma eosinophilic asthma, chronic rhinosinusitis, nasal polyps, mepolizumab, anti-IL5,

PDF

___

1. Flood-Page P, Swenson C, Faiferman I, Matthews J, Williams M et al. International mepolizumab study group. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. American Journal of Respiratory and Critical Care Medicine 2007; 176: 1062-1071.
2. Leckie MJ, ten Brinke A, Khan J, Diamant Z, O’Connor BJ et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness, and the late asthmatic response. Lancet 2000; 356 (9248): 2144-2148.
3. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. New England Journal of Medicine 2014; 371: 1189-1197.
4. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012; 380: 651-659.
5. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM et al. Mepolizumab treatment in patients with severe eosinophilic asthma. New England Journal of Medicine 2014; 371: 1198- 1207.
6. Bousquet J, Chanez P, Lacoste JY, Barnéon G, Ghavanian N et al. Eosinophilic inflammation in asthma. New England Journal of Medicine 1990; 323(15): 1033-1039.
7. Amelink M, de Groot JC, de Nijs SB, Lutter R, Zwinderman AH et al. Severe adult-onset asthma: a distinct phenotype. Journal of Allergy and Clinical Immunology 2013; 132: 336-341.
8. Fajt ML, Wenzel SE. Asthma phenotypes and the use of biologic medications in asthma and allergic disease: the next steps toward personalized care. Journal of Allergy and Clinical Immunology 2015; 135: 299-310.
9. de Groot JC, ten Brinke A, Bel EHD. Management of the patient with eosinophilic asthma: a new era begins. European Respiratory Journal Open Research 2015; 1: 00024-02015.
10. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H et al. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. American Journal of Respiratory and Critical Care Medicine 2010; 181 (4): 315-323.
11. Yilmaz İ, TerI M. Asthma management: a new phenotype based approach using presence of eosinophilia and allergy. Allergy 2017; 72 (10): 1587-1589.
12. Yılmaz İ, Turk M, Bahcecioglu SN. Eosinophilic asthma with nasal polyposis march: is aspirin-exacerbated respiratory disease the last station? Journal of Allergy and Clinical Immunology: In Practice 2017; 5 (6): 1808-1809.
13. Licari A, Brambilla I, De Filippo M, Poddighe D, Castagnoli R et al. The role of upper airway pathology as a co-morbidity in severe asthma. Expert Review of Respiratory Medicine 2017; 11: 855-865.
14. Morita H, Moro K, Koyasu S. Innate lymphoid cells in allergic and non-allergic inflammation. Journal of Allergy and Clinical Immunology 2016; 138: 1253-1264.
15. Drick N, Seeliger B, Welte T, Fuge J, Suhling H. Anti-IL-5 therapy in patients with severe eosinophilic asthma—clinical efficacy and possible criteria for treatment response. BMC Pulmonary Medicine 2018; 18(1): 119.
16. Kurosawa M, Sutoh E. Prospective open-label study of 48- week subcutaneous administration of mepolizumab in Japanese patients with severe eosinophilic asthma. Journal of Investigational Allergology and Clinical Immunology 2019; 29(1): 40-45.
17. Meltzer EO, Hamilos DL. Rhinosinusitis diagnosis and management for the clinician: a synopsis of recent consensus guidelines. Mayo Clinic Proceedings 2011; 86 (5): 427-443.
18. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I et al. EPOS 2012; European position paper on rhinosinusitis and nasal polyps. A summary for otorhinolaryngologists. Rhinology 2012; 50 (1): 1-12.
19. Bachert C, Wagenmann M, Hauser U, Rudack C. IL-5 synthesis is upregulated in human nasal polyp tissue. Journal of Allergy and Clinical Immunology 1997; 99: 837-842.
20. Zhang N, Van Zele T, Perez-Novo C, Van Bruaene N, Holtappels G et al. Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease. Journal of Allergy and Clinical Immunology 2008; 122: 961-968.
21. Tomassen P, Vandeplas G, Van Zele T, Cardell LO, Arebro J et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. Journal of Allergy and Clinical Immunology 2016; 137 (5): 1449-1456.
22. Bachert C, Zhang N, Holtappels G, De Lobel L, van Cauwenberge P et al. Presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in nasal polyps is associated with comorbid asthma. Journal of Allergy and Clinical Immunology 2010; 126: 962-968.
23. Van Zele T, Holtappels G, Gevaert P, Bachert C. Differences in initial immuneprofiles between recurrent and nonrecurrent chronic rhinosinusitis with nasal polyps. American Journal of Rhinology & Allergy 2014; 28: 192-198.
24. Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A et al. Mepolizumab for prednisonedependent asthma with sputum eosinophilia. New England Journal of Medicine 2009; 360: 985-993.
25. Bachert C, Sousa AR, Lund VJ, Scadding GK, Gevaert P et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: randomized trial. Journal of Allergy and Clinical Immunology 2017; 140: 1024-1031.
26. Gevaert P, Van Bruaene N, Cattaert T, Van Steen K, Van Zele T et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. Journal of Allergy and Clinical Immunology 2011; 128: 989-995.
27. Heffler E, Nascimento Girardi Madeira L, Ferrando M, Puggioni F, Racca F et al. Inhaled corticosteroids safety and adverse effects in patients with asthma. Journal of Allergy and Clinical Immunology: In Practice 2018; 3: 2213-2198.
28. Pelaia C, Busceti MT, Solinas S, Terracciano R, Pelaia G. Real-life evaluation of the clinical, functional, and hematological effects of mepolizumab in patients with severe eosinophilic asthma: results of a single-centre observational study. Pulmonary Pharmacology and Therapeutics 2018; 53: 1-5.
29. Yancey SW, Keene ON, Albers FC, Ortega H, Bates S et al. Biomarkers for severe eosinophilic asthma. Journal of Allergy and Clinical Immunology 2017; 140: 1509-1518.
30. Ortega HG, Yancey SW, Mayer B, Gunsoy NB, Keene ON et al. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respiratory Medicine 2016; 4: 549-556.
31. Price DB, Rigazio A, Campbell JD, Bleecker ER, Corrigan CJ et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respiratory Medicine 2015; 3(11): 849-858.
32. Zeiger RS, Schatz M, Li Q, Chen W, Khatry DB et al. High blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma. Journal of Allergy and Clinical Immunology: In Practice 2014; 2(6): 741-750.
33. Gunsoy NB, Cockle SM, Yancey SW, Keene ON, Bradford ES et al. Evaluation of potential continuation rules for mepolizumab treatment of severe eosinophilic asthma. Journal of Allergy and Clinical Immunology: In Practice 2018; 6(3): 874-882.
34. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. Eosinophil’s role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. American Journal of Respiratory and Critical Care Medicine 2003; 167: 199-204.
35. Gerhardsson de verdier M, Gustafson P, McCrae C, Edsbäcker S, Johnston N. Seasonal and geographic variations in the incidence of asthma exacerbations in the United States. Journal Asthma 2017; 54: 818-824.