Chronic rhinosinusitis with nasal polyps; SNOT-22; T2 inflammation; asthma; comorbidity; nasal polyps; real world; severe asthma; Immunology and Allergy
Abstract :
[en] [en] BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) and severe asthma (SA) are 2 frequently coexisting conditions that are, in most cases, associated with eosinophilic inflammation. The concurrence of both diseases has a negative synergistic impact on disease severity and patients' health-related quality of life. Thus, a holistic, collaborative management of these patients is a critical unmet need. Mepolizumab, a systemic anti-IL-5 therapy, has been shown to be effective as an add-on treatment in both SA and CRSwNP, with more literature available on asthma outcomes than on CRSwNP.
OBJECTIVES: The primary objective of the study is to evaluate the real-world effectiveness of mepolizumab in improving the health-related quality of life of comorbid patients at 12 months using the SNOT-22 questionnaire. Secondary objectives include safety and efficacy outcomes of mepolizumab treatment in the 2 populations, which are expected to have variable severity of the respective comorbid conditions.
METHODS: RESPONSE is a European real-world prospective cohort study designed to assess the effectiveness of mepolizumab in 2 cohorts of adult patients: one with SA as primary diagnosis with (secondary diagnosis) comorbid CRSwNP, and another with CRSwNP as primary diagnosis with (secondary diagnosis) comorbid asthma. Up to 350 patients receiving newly prescribed mepolizumab will be followed up for 12 months as per the investigators' standard of care.
CONCLUSION: This study will report the effects of anti-IL-5 therapy in both diseases investigated and the respective comorbidity, as well as the consequence of treating milder forms of asthma and CRSwNP with mepolizumab, supporting the emerging evidence on early treatment optimization.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Bakakos, Petros; 1st University Department of Respiratory Medicine, National and Kapodistrian University of Athens, Athens, Greece
Alobid, Isam; Rhinology and Skull Base Unit, ENT Department, Hospital Clínic, Universitat de Barcelona, CIBERES, IDIBAPS, Barcelona, Spain
Hellings, Peter; Department of Otorhinolaryngology, University Hospitals Leuven, Leuven, Belgium ; Laboratory of Allergy and Clinical Immunology, University of Leuven, Leuven, Belgium ; Upper Airways Research Laboratory, University of Ghent, Ghent, Belgium
Pfaar, Oliver; Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany
Taillé, Camille; Department of Respiratory Diseases, Bichat Hospital, AP-HP Nord-Université Paris Cité, UMR 1152, Paris, France
Bañas-Conejero, David; Specialty Medical Department, GSK, Tres Cantos, Spain
Kallinikou, Konstantina; Europe Medical, Specialty Care, GSK, Athens, Greece
Howarth, Peter; Global Medical, Specialty & Primary Care, GSK, London, United Kingdom
Schleich, Florence ; Université de Liège - ULiège > Département des Sciences de l'activité physique et de la réadaptation > Physiologie humaine et physiologie de l'effort physique
Language :
English
Title :
A RESPONSE to anti-IL-5 therapy in comorbid patients with chronic rhinosinusitis with nasal polyps and severe asthma: Study protocol.
Publication date :
February 2025
Journal title :
The journal of allergy and clinical immunology. Global
Matucci, A., Micheletto, C., Vultaggio, A., Severe asthma and biologics: managing complex patients. J Invest Allergol Clin Immunol 33 (2023), 168–178.
Starry, A., Hardtstock, F., Wilke, T., Weihing, J., Ultsch, B., Wernitz, M., et al. Epidemiology and treatment of patients with chronic rhinosinusitis with nasal polyps in Germany—a claims data study. Allergy 77 (2022), 2725–2736.
Bachert, C., Bhattacharyya, N., Desrosiers, M., Khan, A.H., Burden of disease in chronic rhinosinusitis with nasal polyps. J Asthma Allergy 14 (2021), 127–134.
Heffler, E., Blasi, F., Latorre, M., Menzella, F., Paggiaro, P., Pelaia, G., et al. The Severe Asthma Network in Italy: findings and perspectives. J Allergy Clin Immunol Pract 7 (2019), 1462–1468.
Heaney, L.G., Perez de Llano, L., Al-Ahmad, M., Backer, V., Busby, J., Canonica, G.W., et al. Eosinophilic and noneosinophilic asthma: an expert consensus framework to characterize phenotypes in a global real-life severe asthma cohort. Chest 160 (2021), 814–830.
Azim, A., Newell, C., Barber, C., Harvey, M., Knight, D., Freeman, A., et al. Clinical evaluation of type 2 disease status in a real-world population of difficult to manage asthma using historic electronic healthcare records of blood eosinophil counts. Clin Exp Allergy 51 (2021), 811–820.
Kouro, T., Takatsu, K., IL-5- and eosinophil-mediated inflammation: from discovery to therapy. Int Immunol 21 (2009), 1303–1309.
Gevaert, P., Han, J.K., Smith, S.G., Sousa, A.R., Howarth, P.H., Yancey, S.W., et al. The roles of eosinophils and interleukin-5 in the pathophysiology of chronic rhinosinusitis with nasal polyps. Int Forum Allergy Rhinol 12 (2022), 1413–1423.
Barretto, K.T., Brockman-Schneider, R.A., Kuipers, I., Basnet, S., Bochkov, Y.A., Altman, M.C., et al. Human airway epithelial cells express a functional IL-5 receptor. Allergy 75 (2020), 2127–2130.
Nakayama, T., Yoshikawa, M., Asaka, D., Okushi, T., Matsuwaki, Y., Otori, N., et al. Mucosal eosinophilia and recurrence of nasal polyps—new classification of chronic rhinosinusitis. Rhinology 49 (2011), 392–396.
Bai, J., Huang, J.H., Price, C.P.E., Schauer, J.M., Suh, L.A., Harmon, R., et al. Prognostic factors for polyp recurrence in chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol 150 (2022), 352–361.e7.
Wang, M., Bu, X., Luan, G., Lin, L., Wang, Y., Jin, J., et al. Distinct type 2–high inflammation associated molecular signatures of chronic rhinosinusitis with nasal polyps with comorbid asthma. Clin Transl Allergy, 10, 2020, 26.
Howarth, P., Chupp, G., Nelsen, L.M., Bradford, E.S., Bratton, D.J., Smith, S.G., et al. Severe eosinophilic asthma with nasal polyposis: a phenotype for improved sinonasal and asthma outcomes with mepolizumab therapy. J Allergy Clin Immunol 145 (2020), 1713–1715.
Braunstahl, G.J., Kleinjan, A., Overbeek, S.E., Prins, J.B., Hoogsteden, H.C., Fokkens, W.J., Segmental bronchial provocation induces nasal inflammation in allergic rhinitis patients. Am J Respir Crit Care Med 161 (2000), 2051–2057.
Schleich, F., Moermans, C., Gerday, S., Ziant, S., Louis, G., Bougard, N., et al. Patients with asthma only sensitized to Staphylococcus aureus enterotoxins have more exacerbations, airflow limitation, and higher levels of sputum IL-5 and IgE. J Allergy Clin Immunol Pract 11 (2023), 3055–3061.e4.
Canonica, G.W., Malvezzi, L., Blasi, F., Paggiaro, P., Mantero, M., Senna, G., et al. Chronic rhinosinusitis with nasal polyps impact in severe asthma patients: evidences from the Severe Asthma Network Italy (SANI) registry. Respir Med, 166, 2020, 105947.
Shaw, D.E., Sousa, A.R., Fowler, S.J., Fleming, L.J., Roberts, G., Corfield, J., et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J 46 (2015), 1308–1321.
Pilette, C., Canonica, G.W., Chaudhuri, R., Chupp, G., Lee, F.E., Lee, J.K., et al. REALITI-A study: real-world oral corticosteroid-sparing effect of mepolizumab in severe asthma. J Allergy Clin Immunol Pract 10 (2022), 2646–2656.
Schleich, F., Brusselle, G., Louis, R., Vandenplas, O., Michils, A., Pilette, C., et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir Med 108 (2014), 1723–1732.
Fokkens, W.J., Lund, V.J., Hopkins, C., Hellings, P.W., Kern, R., Reitsma, S., et al. European position paper on rhinosinusitis and nasal polyps, 2020. Rhinology 58:suppl S29 (2020), 1–464.
Bachert, C., Sousa, A.R., Lund, V.J., Scadding, G.K., Gevaert, P., Nasser, S., et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: randomized trial. J Allergy Clin Immunol 140 (2017), 1024–1031.e14.
Denlinger, L.C., Phillips, B.R., Ramratnam, S., Ross, K., Bhakta, N.R., Cardet, J.C., et al. Inflammatory and comorbid features of patients with severe asthma and frequent exacerbations. Am J Respir Crit Care Med 195 (2017), 302–313.
Stevens, W.W., Peters, A.T., Hirsch, A.G., Nordberg, C.M., Schwartz, B.S., Mercer, D.G., et al. Clinical characteristics of patients with chronic rhinosinusitis with nasal polyps, asthma, and aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract 5 (2017), 1061–1070.e3.
Promsopa, C., Kansara, S., Citardi, M.J., Fakhri, S., Porter, P., Luong, A., Prevalence of confirmed asthma varies in chronic rhinosinusitis subtypes. Int Forum Allergy Rhinol 6 (2016), 373–377.
Pearlman, A.N., Chandra, R.K., Chang, D., Conley, D.B., Tripathi-Peters, A., Grammer, L.C., et al. Relationships between severity of chronic rhinosinusitis and nasal polyposis, asthma, and atopy. Am J Rhinol Allergy 23 (2009), 145–148.
Pavord, I.D., Bel, E.H., Bourdin, A., Chan, R., Han, J.K., Keene, O.N., et al. From DREAM to REALITI-A and beyond: mepolizumab for the treatment of eosinophil-driven diseases. Allergy 77 (2022), 778–797.
European Medicines Agency (EMA). Nucala (mepolizumab). EMEA/H/C/003860. Summary of product characteristics. Updated October 2021. Available at: https://www.ema.europa.eu/en/documents/overview/nucala-epar-medicine-overview_en.pdf.
Domingo Ribas, C., Carrillo Díaz, T., Blanco Aparicio, M., Martínez Moragón, E., Banas Conejero, D., Sánchez Herrero, M.G., Real world effectiveness and safety of mepolizumab in a multicentric Spanish cohort of asthma patients stratified by eosinophils: the REDES study. Drugs 81 (2021), 1763–1774.
Taillé, C., Chanez, P., Devouassoux, G., Didier, A., Pison, C., Garcia, G., et al. Mepolizumab in a population with severe eosinophilic asthma and corticosteroid dependence: results from a French early access programme. Eur Respir J, 55, 2020.
Schleich, F., Graff, S., Nekoee, H., Moermans, C., Henket, M., Sanchez, C., et al. Real-word experience with mepolizumab: does it deliver what it has promised?. Clin Exp Allergy 50 (2020), 687–695.
Harvey, E.S., Langton, D., Katelaris, C., Stevens, S., Farah, C.S., Gillman, A., et al. Mepolizumab effectiveness and identification of super-responders in severe asthma. Eur Respir J, 55, 2020, 1902420.
Matucci, A., Vivarelli, E., Bormioli, S., Francesca, N., Chiccoli, F., Valentina, M., et al. Long-term retention rate of mepolizumab treatment in severe asthma: a 36-months real-life experience. J Asthma 60 (2023), 158–166.
Kallieri, M., Zervas, E., Fouka, E., Porpodis, K., Mitrova, M.H., Tzortzaki, E., et al. RELIght: a two-year REal-LIfe study of mepolizumab in patients with severe eosinophilic asTHma in Greece: evaluating the multiple components of response. Allergy 77 (2022), 2848–2852.
Han, J.K., Bachert, C., Fokkens, W., Desrosiers, M., Wagenmann, M., Lee, S.E., et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 9 (2021), 1141–1153.
Orlandi, R.R., Kingdom, T.T., Smith, T.L., Bleier, B., DeConde, A., Luong, A.U., et al. International consensus statement on allergy and rhinology: rhinosinusitis 2021. Int Forum Allergy Rhinol 11 (2021), 213–739.
Fokkens, W.J., Lund, V., Bachert, C., Mullol, J., Bjermer, L., Bousquet, J., et al. EUFOREA consensus on biologics for CRSwNP with or without asthma. Allergy 74 (2019), 2312–2319.
Pfaar, O., Beule, A.G., Laudien, M., Stuck, B.A., [Treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) with monoclonal antibodies (biologics): S2k guideline of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the German College of General Practitioners and Family Physicians (DEGAM)]. HNO 71 (2023), 256–263.
Ortega, H.G., Liu, M.C., Pavord, I.D., Brusselle, G.G., FitzGerald, J.M., Chetta, A., et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 371 (2014), 1198–1207.
Chupp, G.B.E., Albers, F., Bratton, D., Wang-Jairaj, J., Nelsen, L., Trevor, J., Magnan, A., Brinke, A., Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med 5 (2017), 390–400.
Bachert, C., Sousa, A.R., Han, J.K., Schlosser, R.J., Sowerby, L.J., Hopkins, C., et al. Mepolizumab for chronic rhinosinusitis with nasal polyps: treatment efficacy by comorbidity and blood eosinophil count. J Allergy Clin Immunol 149 (2022), 1711–1721.e6.
Liu, M.C., Bagnasco, D., Matucci, A., Pilette, C., Price, R.G., Maxwell, A.C., et al. The impact of comorbid nasal polyps on real-world mepolizumab effectiveness in patients with severe asthma: results from the REALITI-A study (abstract). Am J Respir Crit Care Med, 205, 2022, A4837.
Arismendi, E., Cisneros, C., Blanco-Aparicio, M., Conejero, D.B., Moure, A.L., Sánchez-Herrero, M.G., REDES study: mepolizumab is effective in patients with severe eosinophilic asthma and comorbid NP. Eur Respir J, 60(suppl 66), 2022, 2028.
Moermans, C., Brion, C., Bock, G., Graff, S., Gerday, S., Nekoee, H., et al. Sputum type 2 markers could predict remission in severe asthma treated with anti–IL-5. Chest 163 (2023), 1368–1379.
Bachert, C., Wagenmann, M., Hauser, U., Rudack, C., IL-5 synthesis is upregulated in human nasal polyp tissue. J Allergy Clin Immunol 99:6 pt 1 (1997), 837–842.
Manise, M., Holtappels, G., Van Crombruggen, K., Schleich, F., Bachert, C., Louis, R., Sputum IgE and cytokines in asthma: relationship with sputum cellular profile. PLoS One, 8, 2013, e58388.
Bachert, C., Luong, A.U., Gevaert, P., Mullol, J., Smith, S.G., Silver, J., et al. The unified airway hypothesis: evidence from specific intervention with anti–IL-5 biologic therapy. J Allergy Clin Immunol Pract 11 (2023), 2630–2641.
Laidlaw, T.M., Boyce, J.A., Updates on immune mechanisms in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol 151 (2023), 301–309.
Price, D., Castro, M., Bourdin, A., Fucile, S., Altman, P., Short-course systemic corticosteroids in asthma: striking the balance between efficacy and safety. Eur Respir Rev, 29, 2020.
Lehrer, E., Mullol, J., Agredo, F., Alobid, I., Management of chronic rhinosinusitis in asthma patients: is there still a debate?. Curr Allergy Asthma Rep, 14, 2014, 440.
Alobid, I., Benítez, P., Bernal-Sprekelsen, M., Roca, J., Alonso, J., Picado, C., et al. Nasal polyposis and its impact on quality of life: comparison between the effects of medical and surgical treatments. Allergy 60 (2005), 452–458.
Alobid, I., Cardelus, S., Benítez, P., Guilemany, J.M., Roca-Ferrer, J., Picado, C., et al. Persistent asthma has an accumulative impact on the loss of smell in patients with nasal polyposis. Rhinology 49 (2011), 519–524.
Ehnhage, A., Olsson, P., Kölbeck, K.G., Skedinger, M., Dahlén, B., Alenius, M., et al. Functional endoscopic sinus surgery improved asthma symptoms as well as PEFR and olfaction in patients with nasal polyposis. Allergy 64 (2009), 762–769.
Hauser, L.J., Chandra, R.K., Li, P., Turner, J.H., Role of tissue eosinophils in chronic rhinosinusitis–associated olfactory loss. Int Forum Allergy Rhinol 7 (2017), 957–962.
Tsuda, T., Maeda, Y., Nishide, M., Koyama, S., Hayama, Y., Nojima, S., et al. Eosinophil-derived neurotoxin enhances airway remodeling in eosinophilic chronic rhinosinusitis and correlates with disease severity. Int Immunol 31 (2019), 33–40.
Khan, A., Huynh, T.M.T., Vandeplas, G., Joish, V.N., Mannent, L.P., Tomassen, P., et al. The GALEN rhinosinusitis cohort: chronic rhinosinusitis with nasal polyps affects health-related quality of life. Rhinology 57 (2019), 343–351.
Pavord, I., Gardiner, F., Heaney, L.G., Domingo, C., Price, R.G., Pullan, A., et al. Remission outcomes in severe eosinophilic asthma with mepolizumab therapy: analysis of the REDES study. Front Immunol, 14, 2023, 1150162.
Maza-Solano, J., Calvo-Henríquez, C., Alobid, I., Álvarez-Cendrero, M., Palomares, Ó., Moreno-Luna, R., et al. Nasal symptoms in asthmatic patients under treatment with anti–IL-5 monoclonal antibodies. A real-life cohort study. J Clin Med, 11, 2022, 7056.
Gallo, S., Castelnuovo, P., Spirito, L., Feduzi, M., Seccia, V., Visca, D., et al. Mepolizumab improves outcomes of chronic rhinosinusitis with nasal polyps in severe asthmatic patients: a multicentric real-life study. J Pers Med, 12, 2022, 1304.
Domínguez-Sosa, M.S., Cabrera-Ramírez, M.S., Marrero-Ramos, M.D.C., Dávila-Quintana, D., Cabrera-López, C., Carrillo-Díaz, T., et al. Real-life effectiveness of mepolizumab in refractory chronic rhinosinusitis with nasal polyps. Biomedicines, 11, 2023, 485.
