T2 asthma and T2-associated diseases: a consolidated approach to biological therapy
- Authors: Nenasheva N.M.1
-
Affiliations:
- Federal State Budgetary Educational Institution of Additional Professional Education Russian Medical Academy of Continuous Professional Education
- Issue: Vol 17, No 3 (2020)
- Pages: 34-49
- Section: Reviews
- URL: https://journals.rcsi.science/raj/article/view/121577
- DOI: https://doi.org/10.36691/RJA1390
- ID: 121577
Cite item
Abstract
This article is dedicated to the main characteristics of severe bronchial asthma (SBA) and its heterogeneity. In particular, it describes T2 asthma and the role of the main cytokines involved in T2 inflammation. It focuses on the role of IL-4 and IL-13 in the pathogenesis of asthma and other T2-associated diseases, as key cytokines in the initiation and maintenance of T2 inflammation. The article presents the results of experimental studies proving that the activation of IL-4/IL-13 can cause significant hyperresponsiveness of the human airway smooth muscles and the combined blockade of the activity of these cytokines using a human monoclonal antibody against the common IL-4/13 receptor á-subunit-dupilumab-determines the clinical efficacy not only in relation to exacerbations and control of asthma symptoms, but also an improvement of the lung function and a reduction in bronchial hyperresponsiveness. When type 2 helper cells (Th2) interact with antigen-presenting cells, IL-4 and IL-13 are simultaneously released, therefore, blocking IL-4Rá is more effective than blocking each of the ligands separately, which explains the high efficacy of dupilumab not only in T2 asthma, but also other T2-associated diseases: atopic dermatitis and chronic rhinosinusitis with nasal polyps. In addition to asthma and atopic dermatitis, a new indication for dupilumab, chronic rhinosinusitis with nasal polyps, has recently been approved.
According to the recommendations of the European Academy of Allergy and Clinical Immunology (EAACI) for the biological therapy of SBA 2020, dupilumab is recommended as an add-on maintenance therapy in adults and children aged 12–17 years old with uncontrolled severe T2 asthma, including asthma with the allergic and eosinophilic phenotype, as well as mixed (when there are signs of both phenotypes) and steroid-dependent asthma. At the same time, dupilumab is well tolerated.
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##article.viewOnOriginalSite##About the authors
Natalya M. Nenasheva
Federal State Budgetary Educational Institution of Additional Professional Education Russian Medical Academy of Continuous Professional Education
Author for correspondence.
Email: 1444031@gmail.com
ORCID iD: 0000-0002-3162-2510
Head of Allergology and Immunology Department of Russian Medical Academy of Continuing Professional Education of the Ministry of Health of the Russian Federation, PhD, professor
Russian Federation, MoscowReferences
- Agache I, Akdis CA. Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases. J Clin Invest. 2019;129(4):1493–503. doi: 10.1172/JCI124611
- Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease. Lancet. 2008;372(9643):1107–1119. doi: 10.1016/S0140-6736(08)61452-X
- Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355–360. doi: 10.1016/j.jaci.2010.11.037
- Agache I, Akdis C, Jutel M, Virchow JC. Untangling asthma phenotypes and endotypes. Allergy. 2012;67(7):835–846. doi: 10.1111/j.1398-9995.2012.02832.x
- Agache IO. From phenotypes to endotypes to asthma treatment. Curr Opin Allergy Clin Immunol. 2013;13(3):249–256. doi: 10.1097/ACI.0b013e32836093dd
- Agache I, Akdis CA. Endotypes of allergic diseases and asthma: an important step in building blocks for the future of precision medicine. Allergol Int. 2016;65(3):243–252. doi: 10.1016/j.alit.2016.04.011
- Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009;180(8):796. Corrected and republished from: Am J Respir Crit Care Med. 2009;180(5):388–395. doi: 10.1164/rccm.200903-0392OC
- Bhakta NR, Woodruff PG. Human asthma phenotypes: from the clinic, to cytokines, and back again. Immunol Rev. 2011;242(1):220–232. doi: 10.1111/j.1600-065X.2011.01032.x
- Nenasheva NM. Т2-high and T2-low bronchial asthma, endotype characteristics and biomarkers. Pulmonologiya. 2019;29(2):216–228. (In Russ). doi: 10.18093/0869-0189-2019-29-2-216-228
- Agache I. Severe asthma phenotypes and endotypes. Semin Immunol. 2019;46:101301. doi: 10.1016/j.smim.2019.101301
- Agache I, Sugita K, Morita H, Akdis M, Akdis CA. The complex type 2 endotype in allergy and asthma: from laboratory to bedside. Curr Allergy Asthma Rep. 2015;15(6):29. doi: 10.1007/s11882-015-0529-x
- Agache I, Akdis C, Akdis M, Canonica GW, Casale T, Chivato T, et al. EAACI Biologicals Guidelines – Recommendations for severe asthma. Allergy. 2020:1–31. doi: 10.1111/all.14425
- Sergeeva GR, Emelyanov AV, Korovina OV, Znakhurenko AA, Leshenkova EV, Kozyreva LV, Asatiani N. Severe asthma: characteristics of patients in clinical practice. Terapevticheskii arkhiv. 2015;87(12):26–31 (In Russ.). doi: 10.17116/terarkh2015871226-31
- 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. 2014;108(12):1723–1732. doi: 10.1016/j.rmed.2014.10.007
- Shau DE, Sousa AR, Fowler SJ, Fleming LJ, Robers G, et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J. 2015;46(5):1308–1321. doi: 10.1183/13993003.00779-201
- Gandhi NA, Pirozzi G, Graham NM. 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
- Weinstein SF, Katial R, Jayawardena S, Pirozzi G, Staudinger H, Eckert L, et al. Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma. J Allergy Clin Immunol. 2018;142(1):171–177.e1. doi: 10.1016/j.jaci.2017.11.051
- Jonstam K, Swanson BN, Mannent LP, Cardell LO, Tian N, Wang Y, et al. Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis. Allergy. 2019;74(4):743–752. doi: 10.1111/all.13685
- Furue K, Ito T, Tsuji G, Ulzii D, Vu YH, Kido-Nakahara M, et al. The IL-13-OVOL1-FLG axis in atopic dermatitis. Immunology. 2019;158(4):281–286. doi: 10.1111/imm.13120
- Guttman-Yassky E, Bissonnette R, Ungar B, Suárez-Fariñas M, Ardeleanu M, Esaki H, et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143:155–172. doi: 10.1016/j.jaci.2018.08.022
- Markowitz JE, Jobe L, Miller M, Frost C, Laney Z, Eke R. Safety and efficacy of reslizumab for children and adolescents with eosinophilic esophagitis treated for 9 years. J Pediatr Gastroenterol Nutr. 2018;66(6):893–897. doi: 10.1097/MPG.0000000000001840
- Hirano I, Dellon ES, Hamilton JD, Collins MH, Peterson K, Chehade M, et al. Efficacy of dupilumab in a phase 2 randomized trial of adults with active eosinophilic esophagitis. Gastroenterology. 2020;158(1):111–122.e10. doi: 10.1053/j.gastro.2019.09.042
- Wynn TA. IL-13 effector functions. Annu Rev Immunol. 2003;21:425–456. doi: 10.1146/annurev.immunol.21.120601.141142
- Corren J. Role of interleukin-13 in asthma. Curr Allergy Asthma Rep. 2013;13(5):415–420. doi: 10.1007/s11882-013-0373-9
- Paul WE. History of interleukin-4. Cytokine. 2015;75(1):3–7. doi: 10.1016/j.cyto.2015.01.038
- Punnonen J, Aversa G, Cocks BG, McKenzie AN, Menon S, Zurawski G, et al. Interleukin-13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B-cells. Proc Natl Acad Sci U S A. 1993;90(8):3730–3734. doi: 10.1073/pnas.90.8.3730
- Gascan H, Gauchat JF, Roncarolo MG, Yssel H, Spits H, de Vries JE. Human B-cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T-cell clones. J Exp Med. 1991;173(3):747–750. doi: 10.1084/jem.173.3.747
- Rosenberg HF, Phipps S, Foster PS. Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol. 2007;119(6):1303–1310. doi: 10.1016/j.jaci.2007.03.048
- Le Floc’h A, Allinne J, Nagashima K, Scott G, Birchard D, Asrat S, et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4R antibody, is required to broadly inhibit type 2 inflammation. Allergy. 2020;75(5):1188–1204. doi: 10.1111/all.14151
- Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, 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.
- Rabe KF, Nair P, Brusselle G, Maspero JF, Castro M, Sher L, 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
- Manson ML, Säfholm J, James A, Johnsson AK, Bergman P, Al-Ameri M, et al. IL-13 and IL-4, but not IL-5 nor IL-17A, induce hyperresponsiveness in isolated human small airways. J Allergy Clin Immunol. 2020;145(3):808–817.e2. doi: 10.1016/j.jaci.2019.10.037
- Gandhi NA, Bennett BL, Graham NM, Pirozzi G, Stahl N, Vancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35–50. doi: 10.1038/nrd4624
- Bourdin A, Fabry-Vendrand C, Ostinelli J, Ait-Yahia M, Darnal E, Bouee S, et al. The burden of severe asthma in France: a case-control study using a medical claims database. J Allergy Clin Immunol Pract. 2019;7(5):1477–1487. doi: 10.1016/j.jaip.2018.12.029
- Tiotiu A, Plavec D, Novakova S, Mihaicuta S, Novakova P, Labor M, et al. Current opinions for the management of asthma associated with ear, nose and throat comorbidities. Eur Respir Rev. 2018;27(150):180056. doi: 10.1183/16000617.0056-2018
- Fokkens WJ, Lund VJ, Hopkins C, Hellings PW, Kern R, Reitsma S, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology. 2020;Suppl 29:1–464. doi: 10.4193/Rhin20.600
- Tay TR, Hew M. Comorbid “treatable traits” in difficult asthma: current evidence and clinical evaluation. Allergy. 2018;73:1369–1382. doi: 10.1111/all.13370
- Jarvis D, Newson R, Lotvall J, Hastan D, Tomassen P, Keil T, et al. Asthma in adults and its association with chronic rhinosinusitis: the GA2LEN survey in Europe. Allergy. 2012;67(1):91–98. doi: 10.1111/j.1398-9995.2011.02709.x
- Langdon C, Mullol J. Nasal polyps in patients with asthma: prevalence, impact, and management challenges. J Asthma Allergy. 2016;9:45–53. doi: 10.2147/JAA.S86251
- Nenasheva N, Belevsky A, Kravchenko O, Avdeev S, Emel’yanov A, Kurbacheva O, Leschenko I. Late Breaking Abstract – Preliminary analysis of the data of patients with severe bronchial asthma included in the Russian National Register of Severe Asthma (RSAR). Eur Respir J. 2019;54(Suppl 63):PA4261. doi: 10.1183/13993003.congress-2019.pa4261
- Maspero JF, Katelaris CH, Busse WW, Castro M, Corren J, Chipps BE, et al. Dupilumab efficacy in uncontrolled, moderate-to-severe asthma with self-reported chronic rhinosinusitis. J Allergy Clin Immunol Pract. 2020;8(2):527–539.e9. doi: 10.1016/j.jaip.2019.07.016
- Busse W, Maspero J, Katelaris C, Saralaya D, Guillonneau S, Zhang B, et al. Dupilumab improves SNOT-22 scores in asthma patients with chronic rhinosinusitis or nasal polypsosis (CRS/NP) in LIBERTY ASTHMA QUEST. Eur Respir J. 2018;52(Suppl 62):PA1125. doi: 10.1183/13993003.congress-2018.pa1125
- Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis. JAMA. 2016;315(5):469–479. doi: 10.1001/jama.2015.19330
- Bachert C, Hellings PW, Mullol J, Naclerio RM, Chao J, Amin N, et al. Dupilumab improves patient-reported outcomes in patients with chronic rhinosinusitis with nasal polyps and comorbid asthma. J Allergy Clin Immunol Pract. 2019;7(7):2447–2449. doi: 10.1016/j.jaip.2019.03.023
- Bachert C, Jan JK, Desrosiers M, Hellings PW, Amin N, Lee SE, 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 multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet. 2019;394(10209):1638–1650. doi: 10.1016/S0140-6736(19)31881-1