Pharmacologic Treatment of Type 2-High Severe Asthma

Main Article Content

Annamaria Bosi, MD Maria Serena Simeone, MD Federica Ghinassi, MD Serena Baroncini, MD Valentina Ruggieri, PhD Bianca Beghe, MD, PhD


Asthma is a common and heterogeneous disease whose treatment has considerably changed over the last decades. While inhaled therapies based on inhaled corticosteroids and long acting β2 agonists are effective in controlling asthma in the majority of patients, about 5% of asthmatics poorly respond to inhaled steroids or inhaled steroids/long acting β2 agonists combinations. These patients are affected by “severe asthma”, which is associated with need of oral corticosteroids, progression of the disease, increased use of healthcare services, deterioration of quality of life, and a significant economic burden on society. Asthma is no longer considered a single disease, but a respiratory syndrome with complex biological network of distinct and interrelating inflammatory and remodeling pathways (endotypes) that are associated with different clinical manifestations (phenotypes) both in the lungs (asthma) and other organs (e.g. nose and skin). Severe asthma endotypes may be broadly regarded as Type 2-high and Type 2-low, a model that has become central to asthma management with the development of novel treatments for the Type 2-high endotypes. The hallmark feature of Type 2-high asthma is eosinophilic inflammation, often associated with increased serum IgE, increased exhaled nitric oxide (FeNO) and blood eosinophilia. The discovery of the main key drivers of Type 2-high inflammation (IgE, cytokines such as interleukin IL-5, -4 and -13) enabled the development of new biological agents directed towards specific molecular targets. These advances have shifted the existing paradigm “one drug fits all” to “patient-tailored” novel therapies. The monoclonal antibodies direct to IgE (omalizumab), IL-5 and IL-5 receptor (mepolizumab, benralizumab, reslizumab), and to the α chain of the IL-4 and IL-13 combined receptor (dupilumab), and more recently, to the thymic stromal lymphopoietin (tezepelumab) have been shown in both clinical trials and real-life studies to control symptoms, reduce asthma exacerbations and improve lung function in severe asthmatics not controlled by full inhalation therapies. More recently, the Single Inhaler Triple Therapy (SITT) containing inhaled steroids, long acting β2 agonists and muscarinic antagonists has been developed, slightly improving the effectiveness/safety of the inhalation therapy. This report aims to review available therapeutic opportunities for patients with severe asthma focusing on patients with Type 2-high severe asthma and how to position these new therapeutic alternatives in clinical practice.

Keywords: Biologics, monoclonal antibodies, lung function, exacerbations, airways inflammation

Article Details

How to Cite
BOSI, Annamaria et al. Pharmacologic Treatment of Type 2-High Severe Asthma. Medical Research Archives, [S.l.], v. 12, n. 4, may 2024. ISSN 2375-1924. Available at: <>. Date accessed: 27 may 2024. doi:
Research Articles


1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2023. Updated July 2023.
2. Settipane RA, Kreindler JL, Chung Y, Tkacz J. Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States. Ann Allergy Asthma Immunol. 2019;123(6):564-572.e3. Doi:10.1016/j.anai.2019.08.462
3. Wenzel SE. Severe Adult Asthmas: Integrating Clinical Features, Biology, and Therapeutics to Improve Outcomes. Am J Respir Crit Care Med. 2021;203(7):809-821. Doi:10.1164/rccm.202009-3631CI
4. Israel E, Reddel HK. Severe and Difficult-to-Treat Asthma in Adults. Drazen JM, ed. N Engl J Med. 2017;377(10):965-976. Doi:10.1056/NEJMra1608969
5. Brusselle GG, Koppelman GH. Biologic Therapies for Severe Asthma. Taichman DB, ed. N Engl J Med. 2022;386(2):157-171. Doi:10.1056/NEJMra2032506
6. Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55(1):1900588. Doi:10.1183/13993003.00588-2019
7. Wenzel SE, Schwartz LB, Langmack EL, et al. Evidence That Severe Asthma Can Be Divided Pathologically into Two Inflammatory Subtypes with Distinct Physiologic and Clinical Characteristics. Am J Respir Crit Care Med. 1999;160(3):1001-1008. Doi:10.1164/ajrccm.160.3.9812110
8. Kuruvilla ME, Lee FEH, Lee GB. Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease. Clin Rev Allergy Immunol. 2019;56(2):219-233. Doi:10.1007/s12016-018-8712-1
9. Fahy JV. Type 2 inflammation in asthma — present in most, absent in many. Nat Rev Immunol. 2015;15(1):57-65. Doi:10.1038/nri3786
10. Caminati M, Pham DL, Bagnasco D, Canonica GW. Type 2 immunity in asthma. World Allergy Organ J. 2018;11:13. Doi:10.1186/s40413-018-0192-5
11. Robinson D, Humbert M, Buhl R, et al. Revisiting T ype 2‐high and T ype 2‐low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017;47(2):161-175. Doi:10.1111/cea.12880
12. Corren J, Parnes JR, Wang L, et al. Tezepelumab in Adults with Uncontrolled Asthma. N Engl J Med. 2017;377(10):936-946. Doi:10.1056/NEJMoa1704064
13. Hinks TSC, Levine SJ, Brusselle GG. Treatment options in type-2 low asthma. Eur Respir J. 2021;57(1):2000528. Doi:10.1183/13993003.00528-2020
14. Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020;24(8):777-792. Doi:10.1080/14728222.2020.1783242
15. Busse WW, Kraft M, Rabe KF, et al. Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation. Eur Respir J. 2021;58(2):2003393. Doi:10.1183/13993003.03393-2020
16. Charles D, Shanley J, Temple S, Rattu A, Khaleva E, Roberts G. Real‐world efficacy of treatment with benralizumab, dupilumab, mepolizumab and reslizumab for severe asthma: A systematic review and meta‐analysis. Clin Exp Allergy. 2022;52(5):616-627. Doi:10.1111/cea.14112
17. Grunstein MM, Hakonarson H, Leiter J, et al. IL-13-dependent autocrine signaling mediates altered responsiveness of IgE-sensitized airway smooth muscle. Am J Physiol-Lung Cell Mol Physiol. 2002;282(3):L520-L528. Doi:10.1152/ajplung.00343.2001
18. Mummadi SR, Hahn PY. Update on Exhaled Nitric Oxide in Clinical Practice. Chest. 2016;149(5):1340-1344. Doi:10.1016/j.chest.2015.11.020
19. Porsbjerg C, Melén E, Lehtimäki L, Shaw D. Asthma. The Lancet. 2023;401(10379):858-873. Doi:10.1016/S0140-6736(22)02125-0
20. Tang M, Elicker BM, Henry T, et al. Mucus Plugs Persist in Asthma, and Changes in Mucus Plugs Associate with Changes in Airflow over Time. Am J Respir Crit Care Med. 2022;205(9):1036-1045. Doi:10.1164/rccm.202110-2265OC
21. Popović-Grle S, Štajduhar A, Lampalo M, Rnjak D. Biomarkers in Different Asthma Phenotypes. Genes. 2021;12(6):801. Doi:10.3390/genes12060801
22. Woo SD, Park HS, Jang JH, et al. Biomarkers for predicting type 2-high and uncontrolled asthma in real-world practice. Ann Allergy Asthma Immunol. 2023;131(2):209-216.e2. Doi:10.1016/j.anai.2023.05.011
23. Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. The Lancet. 2012;380(9842):651-659. Doi:10.1016/S0140-6736(12)60988-X
24. Bleecker ER, Wechsler ME, FitzGerald JM, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52(4):1800936. Doi:10.1183/13993003.00936-2018
25. Guida G, Bertolini F, Carriero V, et al. Reliability of Total Serum IgE Levels to Define Type 2 High and Low Asthma Phenotypes. J Clin Med. 2023;12(17):5447. Doi:10.3390/jcm12175447
26. Denton E, Price DB, Tran TN, et al. Cluster Analysis of Inflammatory Biomarker Expression in the International Severe Asthma Registry. J Allergy Clin Immunol Pract. 2021;9(7):2680-2688.e7. Doi:10.1016/j.jaip.2021.02.059
27. Fitzpatrick AM, Chipps BE, Holguin F, Woodruff PG. T2-“Low” Asthma: Overview and Management Strategies. J Allergy Clin Immunol Pract. 2020;8(2):452-463. Doi:10.1016/j.jaip.2019.11.006
28. Yao X, Barochia AV, Levine SJ. What’s on the Horizon for the Targeted Treatment of Type 2-low Asthma? Chest. 2023;163(6):1362-1364. Doi:10.1016/j.chest.2022.12.017
29. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2015.
30. Rogliani P, Ritondo BL, Calzetta L. Triple therapy in uncontrolled asthma: a network meta-analysis of phase III studies. Eur Respir J. 2021;58(3):2004233. Doi:10.1183/13993003.04233-2020
31. Agusti A, Fabbri L, Lahousse L, Singh D, Papi A. Single inhaler triple therapy (SITT) in asthma: Systematic review and practice implications. Allergy. 2022;77(4):1105-1113. Doi:10.1111/all.15076
32. Gosens R, Gross N. The mode of action of anticholinergics in asthma. Eur Respir J. 2018;52(4):1701247. Doi:10.1183/13993003.01247-2017
33. Cazzola M, Puxeddu E, Matera MG, Rogliani P. A potential role of triple therapy for asthma patients. Expert Rev Respir Med. 2019;13(11):1079-1085. Doi:10.1080/17476348.2019.1657408
34. Casale TB, Bateman ED, Vandewalker M, et al. Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype. J Allergy Clin Immunol Pract. 2018;6(3):923-935.e9. Doi:10.1016/j.jaip.2017.08.037
35. Kerstjens HAM, Engel M, Dahl R, et al. Tiotropium in Asthma Poorly Controlled with Standard Combination Therapy. N Engl J Med. 2012;367(13):1198-1207. Doi:10.1056/NEJMoa1208606
36. Hamelmann E, Bernstein JA, Vandewalker M, et al. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017;49(1):1601100. Doi:10.1183/13993003.01100-2016
37. Virchow JC, Kuna P, Paggiaro P, et al. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials. The Lancet. 2019;394(10210):1737-1749. Doi:10.1016/S0140-6736(19)32215-9
38. Kerstjens HAM, Maspero J, Chapman KR, et al. Once-daily, single-inhaler mometasone–indacaterol–glycopyrronium versus mometasone–indacaterol or twice-daily fluticasone–salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study. Lancet Respir Med. 2020;8(10):1000-1012. Doi:10.1016/S2213-2600(20)30190-9
39. Gessner C, Kornmann O, Maspero J, et al. Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON). Respir Med. 2020;170:106021. Doi:10.1016/j.rmed.2020.106021
40. Lee LA, Bailes Z, Barnes N, et al. Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial. Lancet Respir Med. 2021;9(1):69-84. Doi:10.1016/S2213-2600(20)30389-1
41. Kim LHY, Saleh C, Whalen-Browne A, O’Byrne PM, Chu DK. Triple vs Dual Inhaler Therapy and Asthma Outcomes in Moderate to Severe Asthma: A Systematic Review and Meta-analysis. JAMA. 2021;325(24):2466. Doi:10.1001/jama.2021.7872
42. Busse WW, Abbott CB, Germain G, et al. Adherence and Persistence to Single-Inhaler Versus Multiple-Inhaler Triple Therapy for Asthma Management. J Allergy Clin Immunol Pract. 2022;10(11):2904-2913.e6. Doi:10.1016/j.jaip.2022.06.010
43. Singh D, Virchow JC, Canonica GW, et al. Extrafine triple therapy in patients with asthma and persistent airflow limitation. Eur Respir J. 2020;56(3):2000476. Doi:10.1183/13993003.00476-2020
44. Walsh GM. Anti-IL-5 monoclonal antibodies for the treatment of asthma: an update. Expert Opin Biol Ther. 2020;20(10):1237-1244. Doi:10.1080/14712598.2020.1782381
45. Thomson NC, Chaudhuri R. Omalizumab: Clinical Use for the Management of Asthma. Clin Med Insights Circ Respir Pulm Med. 2012;6:CCRPM.S7793. Doi:10.4137/CCRPM.S7793
46. Solèr M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18(2):254-261. Doi:10.1183/09031936.01.00092101
47. Busse W, Corren J, Lanier BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184-190. Doi:10.1067/mai.2001.117880
48. Humbert M, Beasley R, Ayres J, et al. Benefits of omalizumab as add‐on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60(3):309-316. Doi:10.1111/j.1398-9995.2004.00772.x
49. Siergiejko Z, Świebocka E, Smith N, et al. Oral corticosteroid sparing with omalizumab in severe allergic (IgE-mediated) asthma patients. Curr Med Res Opin. 2011;27(11):2223-2228. Doi:10.1185/03007995.2011.620950
50. Hanania NA, Wenzel S, Rosén K, et al. Exploring the Effects of Omalizumab in Allergic Asthma: An Analysis of Biomarkers in the EXTRA Study. Am J Respir Crit Care Med. 2013;187(8):804-811. Doi:10.1164/rccm.201208-1414OC
51. Iribarren C, Rahmaoui A, Long AA, et al. Cardiovascular and cerebrovascular events among patients receiving omalizumab: Results from EXCELS, a prospective cohort study in moderate to severe asthma. J Allergy Clin Immunol. 2017;139(5):1489-1495.e5. Doi:10.1016/j.jaci.2016.07.038
52. Braunstahl GJ, Chen CW, Maykut R, Georgiou P, Peachey G, Bruce J. The eXpeRience registry: The ‘real-world’ effectiveness of omalizumab in allergic asthma. Respir Med. 2013;107(8):1141-1151. Doi:10.1016/j.rmed.2013.04.017
53. Al Ahmad M, Borboa Olivares LM, Cardoso AP, et al. Real-life Effectiveness of Omalizumab in Patients with Severe Allergic Asthma: RELIEF Study. Open Respir Med J. 2022;16(1):e187430642206130. Doi:10.2174/18743064-v16-e2206130
54. Humbert M, Taillé C, Mala L, Le Gros V, Just J, Molimard M. Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: the STELLAIR study. Eur Respir J. 2018;51(5):1702523. Doi:10.1183/13993003.02523-2017
55. Gevaert P, Omachi TA, Corren J, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol. 2020;146(3):595-605. Doi:10.1016/j.jaci.2020.05.032
56. AIFA. Allegato 1- Riassunto delle caratteristiche del prodotto.
57. Pelaia C, Vatrella A, Busceti MT, et al. Severe eosinophilic asthma: from the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab. Drug Des Devel Ther. 2017;Volume 11:3137-3144. Doi:10.2147/DDDT.S150656
58. Food and Drug Administration. Mepolizumab full prescribing information.,125526s019lbl.pdf
59. Flood-Page P, Swenson C, Faiferman I, et al. A Study to Evaluate Safety and Efficacy of Mepolizumab in Patients with Moderate Persistent Asthma. Am J Respir Crit Care Med. 2007;176(11):1062-1071. Doi:10.1164/rccm.200701-085OC
60. Pavord ID, Brightling CE, Woltmann G, Wardlaw AJ. Non-eosinophilic cor ticosteroid unresponsive asthma. The Lancet. 1999;353(9171):2213-2214. Doi:10.1016/S0140-6736(99)01813-9
61. Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma. N Engl J Med. 2009;360(10):973-984. Doi:10.1056/NEJMoa0808991
62. Nair P, Pizzichini MMM, Kjarsgaard M, et al. Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. N Engl J Med. 2009;360(10):985-993. Doi:10.1056/NEJMoa0805435
63. Ortega HG, Liu MC, Pavord ID, et al. Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma. N Engl J Med. 2014;371(13):1198-1207. Doi:10.1056/NEJMoa1403290
64. Bel EH, Wenzel SE, Thompson PJ, et al. Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma. N Engl J Med. 2014;371(13):1189-1197. Doi:10.1056/NEJMoa1403291
65. Lugogo N, Domingo C, Chanez P, et al. Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study. Clin Ther. 2016;38(9):2058-2070.e1. Doi:10.1016/j.clinthera.2016.07.010
66. Khurana S, Brusselle GG, Bel EH, et al. Long-term Safety and Clinical Benefit of Mepolizumab in Patients With the Most Severe Eosinophilic Asthma: The COSMEX Study. Clin Ther. 2019;41(10):2041-2056.e5. Doi:10.1016/j.clinthera.2019.07.007
67. Khatri S, Moore W, Gibson PG, et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2019;143(5):1742-1751.e7. Doi:10.1016/j.jaci.2018.09.033
68. Pilette C, Canonica GW, Chaudhuri R, et al. REALITI-A Study: Real-World Oral Corticosteroid-Sparing Effect of Mepolizumab in Severe Asthma. J Allergy Clin Immunol Pract. 2022;10(10):2646-2656. Doi:10.1016/j.jaip.2022.05.042
69. Domingo Ribas C, Carrillo Díaz T, Blanco Aparicio M, et al. REal worlD Effectiveness and Safety of Mepolizumab in a Multicentric Spanish Cohort of Asthma Patients Stratified by Eosinophils: The REDES Study. Drugs. 2021;81(15):1763-1774. Doi:10.1007/s40265-021-01597-9
70. Domvri K, Tsiouprou I, Bakakos P, et al. Effect of Mepolizumab on airways remodeling in patients with late-onset severe eosinophilic asthma and fixed obstruction (preliminary data of the MESILICO study). In: Monitoring Airway Disease. European Respiratory Society; 2023:OA3152. Doi:10.1183/13993003.congress-2023.OA3152
71. Moore WC, Kornmann O, Humbert M, et al. Stopping versus continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study). Eur Respir J. 2022;59(1):2100396. Doi:10.1183/13993003.00396-2021
72. Pelaia C, Vatrella A, Bruni A, Terracciano R, Pelaia G. Benralizumab in the treatment of severe asthma: design, development and potential place in therapy. Drug Des Devel Ther. 2018;Volume 12:619-628. Doi:10.2147/DDDT.S155307
73. Bergantini L, d’Alessandro M, Pianigiani T, Cekorja B, Bargagli E, Cameli P. Benralizumab affects NK cell maturation and proliferation in severe asthmatic patients. Clin Immunol. 2023;253:109680. Doi:10.1016/j.clim.2023.109680
74. 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 β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. The Lancet. 2016;388(10056):2115-2127. Doi:10.1016/S0140-6736(16)31324-1
75. 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. The Lancet. 2016;388(10056):2128-2141. Doi:10.1016/S0140-6736(16)31322-8
76. Nair P, Wenzel S, Rabe KF, et al. Oral Glucocorticoid–Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017;376(25):2448-2458. Doi:10.1056/NEJMoa1703501
77. Busse WW, Bleecker ER, FitzGerald JM, et al. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med. 2019;7(1):46-59. Doi:10.1016/S2213-2600(18)30406-5
78. Korn S, Bourdin A, Chupp G, et al. Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to 5 Years. J Allergy Clin Immunol Pract. 2021;9(12):4381-4392.e4. Doi:10.1016/j.jaip.2021.07.058
79. Menzies-Gow A, Gurnell M, Heaney LG, et al. Oral corticosteroid elimination via a personalised reduction algorithm in adults with severe, eosinophilic asthma treated with benralizumab (PONENTE): a multicentre, open-label, single-arm study. Lancet Respir Med. 2022;10(1):47-58. Doi:10.1016/S2213-2600(21)00352-0
80. Menzella F, Bargagli E, Aliani M, et al. ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study. Respir Res. 2022;23(1):36. Doi:10.1186/s12931-022-01952-8
81. Vultaggio A, Aliani M, Altieri E, et al. Long-term effectiveness of benralizumab in severe eosinophilic asthma patients treated for 96-weeks: data from the ANANKE study. Respir Res. 2023;24(1):135. Doi:10.1186/s12931-023-02439-w
82. D’Amato M, Menzella F, Altieri E, et al. Benralizumab in Patients With Severe Eosinophilic Asthma With and Without Chronic Rhinosinusitis With Nasal Polyps: An ANANKE Study post-hoc Analysis. Front Allergy. 2022;3:881218. Doi:10.3389/falgy.2022.881218
83. Senna G, Aliani M, Altieri E, et al. Clinical Features and Efficacy of Benralizumab in Patients with Blood Eosinophil Count Between 300 and 450 Cells/mm3: A Post Hoc Analysis from the ANANKE Study. J Asthma Allergy. 2022;Volume 15:1593-1604. Doi:10.2147/JAA.S383012
84. Caruso C, Cameli P, Altieri E, et al. Switching from one biologic to benralizumab in patients with severe eosinophilic asthma: An ANANKE study post hoc analysis. Front Med. 2022;9:950883. Doi:10.3389/fmed.2022.950883
85. 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(3):260-274. Doi:10.1016/S2213-2600(20)30414-8
86. van der Valk JPM, Hekking PP, Rauh SP, et al. Anti-IL-5/5Ra biologics improve work productivity and activity in severe asthma: a RAPSODI registry-based cohort study. J Asthma. 2023;60(10):1869-1876. Doi:10.1080/02770903.2023.2196563
87. Sposato B, Scalese M, Camiciottoli G, et al. Severe asthma and long-term Benralizumab effectiveness in real-life. Eur Rev Med Pharmacol Sci. 2022;26(20):7461-7473. Doi:10.26355/eurrev_202210_30016
88. Jackson DJ, Heaney LG, Humbert M, et al. Reduction of daily maintenance inhaled corticosteroids in patients with severe eosinophilic asthma treated with benralizumab (SHAMAL): a randomised, multicentre, open-label, phase 4 study. The Lancet. Published online December 2023:S0140673623022845. Doi:10.1016/S0140-6736(23)02284-5
89. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med. 2017;376(11):1090-1091. Doi:10.1056/NEJMc1700366
90. Bachert C, Han JK, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. The Lancet. 2019;394(10209):1638-1650. Doi:10.1016/S0140-6736(19)31881-1
91. Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol. 2017;13(5):425-437. Doi:10.1080/1744666X.2017.1298443
92. Harb H, Chatila TA. Mechanisms of Dupilumab. Clin Exp Allergy. 2020;50(1):5-14. Doi:10.1111/cea.13491
93. Gandhi NA, Bennett BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50. Doi:10.1038/nrd4624
94. Wenzel S, Ford L, Pearlman D, et al. Dupilumab in Persistent Asthma with Elevated Eosinophil Levels. N Engl J Med. 2013;368(26):2455-2466. Doi:10.1056/NEJMoa1304048
95. Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. The Lancet. 2016;388(10039):31-44. Doi:10.1016/S0140-6736(16)30307-5
96. Castro M, Corren J, Pavord ID, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med. 2018;378(26):2486-2496. Doi:10.1056/NEJMoa1804092
97. Rabe KF, Nair P, Brusselle G, et al. Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med. 2018;378(26):2475-2485. Doi:10.1056/NEJMoa1804093
98. Caminati M, Olivieri B, Dama A, et al. Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management. Expert Rev Respir Med. 2022;16(7):713-721. Doi:10.1080/17476348.2022.2090342
99. Wechsler ME, Ford LB, Maspero JF, et al. Long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma (TRAVERSE): an open-label extension study. Lancet Respir Med. 2022;10(1):11-25. Doi:10.1016/S2213-2600(21)00322-2
100. Campisi R, Crimi C, Nolasco S, et al. Real-World Experience with Dupilumab in Severe Asthma: One-Year Data from an Italian Named Patient Program. J Asthma Allergy. 2021;Volume 14:575-583. Doi:10.2147/JAA.S312123
101. Dupin C, Belhadi D, Guilleminault L, et al. Effectiveness and safety of dupilumab for the treatment of severe asthma in a real‐life French multi‐centre adult cohort. Clin Exp Allergy. 2020;50(7):789-798. Doi:10.1111/cea.13614
102. Pelaia C, Benfante A, Busceti MT, et al. Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps. Front Immunol. 2023;14:1121237. Doi:10.3389/fimmu.2023.1121237
103. Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021;384(19):1800-1809. Doi:10.1056/NEJMoa2034975
104. Wechsler ME, Menzies-Gow A, Brightling CE, et al. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study. Lancet Respir Med. 2022;10(7):650-660. Doi:10.1016/S2213-2600(21)00537-3
105. AstraZeneca. Study to Evaluate Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma (WAYFINDER), NCT05274815.
106. AstraZeneca. Tezepelumab Efficacy and Safety in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (SUNRISE), NCT05398263.
107. Menzies-Gow A, Wechsler ME, Brightling CE, et al. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. Lancet Respir Med. 2023;11(5):425-438. Doi:10.1016/S2213-2600(22)00492-1
108. Diver S, Khalfaoui L, Emson C, et al. Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9(11):1299-1312. Doi:10.1016/S2213-2600(21)00226-5
109. Sverrild A, Hansen S, Hvidtfeldt M, et al. The effect of tezepelumab on airway hyperresponsiveness to mannitol in asthma (UPSTREAM). Eur Respir J. 2022;59(1):2101296. Doi:10.1183/13993003.01296-2021
110. Busse WW. The Relationship of Airway Hyperresponsiveness and Airway Inflammation. Chest. 2010;138(2):4S-10S. Doi:10.1378/chest.10-0100
111. Porsbjerg CM, Sverrild A, Lloyd CM, Menzies-Gow AN, Bel EH. Anti-alarmins in asthma: targeting the airway epithelium with next-generation biologics. Eur Respir J. 2020;56(5):2000260. Doi:10.1183/13993003.00260-2020
112. Wechsler ME, Ruddy MK, Pavord ID, et al. Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. N Engl J Med. 2021;385(18):1656-1668. Doi:10.1056/NEJMoa2024257
113. Kelsen SG, Agache IO, Soong W, et al. Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial. J Allergy Clin Immunol. 2021;148(3):790-798. Doi:10.1016/j.jaci.2021.03.044
114. Weidinger S, Bieber T, Cork MJ, et al. Safety and efficacy of amlitelimab, a fully human nondepleting, noncytotoxic anti-OX40 ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomized placebo-controlled trial. Br J Dermatol. 2023;189(5):531-539. Doi:10.1093/bjd/ljad240
115. Sanofi. Long-term Safety and Efficacy Evaluation of Subcutaneous Amlitelimab in Adult Participants With Moderatetosevere Asthma Who Completed Treatment Period of Previous Amlitelimab Asthma Clinical Study (RIVER-ASTHMA), NCT06033833.
116. GlaxoSmithKline. Placebo-controlled Efficacy and Safety Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-1), NCT04719832.
117. GlaxoSmithKline. A Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype (SWIFT-2), NCT04718103.
118. GlaxoSmithKline. A Study of GSK3511294 (Depemokimab) Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype (NIMBLE), NCT04718389.
119. Dragonieri S, Carpagnano GE. Biological therapy for severe asthma. Asthma Res Pract. 2021;7(1):12. Doi:10.1186/s40733-021-00078-w