DOI QR코드

DOI QR Code

Tailored Biologics Selection in Severe Asthma

  • Sang Hyuk Kim (Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Dongguk University Gyeongju Hospital, Dongguk University College of Medicine) ;
  • Youlim Kim (Division of Pulmonary and Allergy, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine)
  • Received : 2023.07.21
  • Accepted : 2023.11.22
  • Published : 2024.01.31

Abstract

The management of severe asthma presents a significant challenge in asthma treatment. Over the past few decades, remarkable progress has been made in developing new treatments for severe asthma, primarily in the form of biological agents. These advances have been made possible through a deeper understanding of the underlying pathogenesis of asthma. Most biological agents focus on targeting specific inflammatory pathways known as type 2 inflammation. However, recent developments have introduced a new agent targeting upstream alarmin signaling pathways. This opens up new possibilities, and it is anticipated that additional therapeutic agents targeting various pathways will be developed in the future. Despite this recent progress, the mainstay of asthma treatment has long been inhalers. As a result, the guidelines for the appropriate use of biological agents are not yet firmly established. In this review, we aim to emphasize the current state of biological therapy for severe asthma and provide insights into its future prospects.

Keywords

References

  1. Papi A, Brightling C, Pedersen SE, Reddel HK. Asthma. Lancet 2018;391:783-800. https://doi.org/10.1016/S0140-6736(17)33311-1
  2. Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43:343-73. https://doi.org/10.1183/09031936.00202013
  3. Hekking PW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol 2015;135:896-902. https://doi.org/10.1016/j.jaci.2014.08.042
  4. Robinson DS. Assessing severe asthma. Eur Respir J 2016;48:611-3. https://doi.org/10.1183/13993003.01034-2016
  5. Fahy JV. Type 2 inflammation in asthma: present in most, absent in many. Nat Rev Immunol 2015;15:57-65. https://doi.org/10.1038/nri3786
  6. Hudey SN, Ledford DK, Cardet JC. Mechanisms of nontype 2 asthma. Curr Opin Immunol 2020;66:123-8. https://doi.org/10.1016/j.coi.2020.10.002
  7. Brusselle GG, Koppelman GH. Biologic therapies for severe asthma. N Engl J Med 2022;386:157-71. https://doi.org/10.1056/NEJMra2032506
  8. Strunk RC, Bloomberg GR. Omalizumab for asthma. N Engl J Med 2006;354:2689-95. https://doi.org/10.1056/NEJMct055184
  9. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med 2014;371:1198-207. https://doi.org/10.1056/NEJMoa1403290
  10. Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker 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. Lancet 2016;388:2115-27. https://doi.org/10.1016/S0140-6736(16)31324-1
  11. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med 2015;3:355-66. https://doi.org/10.1016/S2213-2600(15)00042-9
  12. 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;378:2486-96. https://doi.org/10.1056/NEJMoa1804092
  13. Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol 2019;56:219-33. https://doi.org/10.1007/s12016-018-8712-1
  14. Caminati M, Pham DL, Bagnasco D, Canonica GW. Type 2 immunity in asthma. World Allergy Organ J 2018;11:13.
  15. Lugogo NL, Akuthota P. Type 2 biomarkers in asthma: yet another reflection of heterogeneity. J Allergy Clin Immunol Pract 2021;9:1276-7. https://doi.org/10.1016/j.jaip.2020.12.032
  16. Choy DF, Hart KM, Borthwick LA, Shikotra A, Nagarkar DR, Siddiqui S, et al. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. Sci Transl Med 2015;7:301ra129.
  17. Wang YH, Wills-Karp M. The potential role of interleukin-17 in severe asthma. Curr Allergy Asthma Rep 2011;11:388-94. https://doi.org/10.1007/s11882-011-0210-y
  18. Ricciardolo FLM, Sprio AE, Baroso A, Gallo F, Riccardi E, Bertolini F, et al. Characterization of T2-low and T2-high asthma phenotypes in real-life. Biomedicines 2021;9:1684.
  19. Kyriakopoulos C, Gogali A, Bartziokas K, Kostikas K. Identification and treatment of T2-low asthma in the era of biologics. ERJ Open Res 2021;7:00309-2020.
  20. Hinks TSC, Levine SJ, Brusselle GG. Treatment options in type-2 low asthma. Eur Respir J 2021;57:2000528.
  21. Porsbjerg C, Melen E, Lehtimaki L, Shaw D. Asthma. Lancet 2023;401:858-73. https://doi.org/10.1016/S0140-6736(22)02125-0
  22. Hanania NA, Alpan O, Hamilos DL, Condemi JJ, Reyes-Rivera I, Zhu J, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial. Ann Intern Med 2011;154:573-82. https://doi.org/10.7326/0003-4819-154-9-201105030-00002
  23. Porsbjerg CM, Menzies-Gow AN, Tran TN, Murray RB, Unni B, Audrey Ang SL, et al. Global variability in administrative approval prescription criteria for biologic therapy in severe asthma. J Allergy Clin Immunol Pract 2022;10:1202-16. https://doi.org/10.1016/j.jaip.2021.12.027
  24. Pelaia C, Paoletti G, Puggioni F, Racca F, Pelaia G, Canonica GW, et al. Interleukin-5 in the pathophysiology of severe asthma. Front Physiol 2019;10:1514.
  25. Tran TN, Zeiger RS, Peters SP, Colice G, Newbold P, Goldman M, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol 2016;116:37-42. https://doi.org/10.1016/j.anai.2015.10.027
  26. Saglani S, Lloyd CM. Novel concepts in airway inflammation and remodelling in asthma. Eur Respir J 2015;46:1796-804. https://doi.org/10.1183/13993003.01196-2014
  27. Bagnasco D, Menzella F, Caminati M, Caruso C, Guida G, Bonavia M, et al. Efficacy of mepolizumab in patients with previous omalizumab treatment failure: real-life observation. Allergy 2019;74:2539-41. https://doi.org/10.1111/all.13937
  28. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med 2014;371:1189-97. https://doi.org/10.1056/NEJMoa1403291
  29. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 2012;380:651-9. https://doi.org/10.1016/S0140-6736(12)60988-X
  30. Ghassemian A, Park JJ, Tsoulis MW, Kim H. Targeting the IL-5 pathway in eosinophilic asthma: a comparison of mepolizumab to benralizumab in the reduction of peripheral eosinophil counts. Allergy Asthma Clin Immunol 2021;17:3.
  31. 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 Pulm Med 2018;18:119.
  32. Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy 2020;50:5-14. https://doi.org/10.1111/cea.13491
  33. Sher LD, Wechsler ME, Rabe KF, Maspero JF, Daizadeh N, Mao X, et al. Dupilumab reduces oral corticosteroid use in patients with corticosteroid-dependent severe asthma: an analysis of the phase 3, open-label extension TRAVERSE trial. Chest 2022;162:46-55. https://doi.org/10.1016/j.chest.2022.01.071
  34. Oykhman P, Paramo FA, Bousquet J, Kennedy DW, Brignardello-Petersen R, Chu DK. Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: a systematic review and network meta-analysis. J Allergy Clin Immunol 2022;149:1286-95. https://doi.org/10.1016/j.jaci.2021.09.009
  35. Laidlaw TM, Bachert C, Amin N, Desrosiers M, Hellings PW, Mullol J, et al. Dupilumab improves upper and lower airway disease control in chronic rhinosinusitis with nasal polyps and asthma. Ann Allergy Asthma Immunol 2021;126:584-92. https://doi.org/10.1016/j.anai.2021.01.012
  36. Hoy SM. Tezepelumab: first approval. Drugs 2022;82:461-8. https://doi.org/10.1007/s40265-022-01679-2
  37. Tanaka J, Watanabe N, Kido M, Saga K, Akamatsu T, Nishio A, et al. Human TSLP and TLR3 ligands promote differentiation of Th17 cells with a central memory phenotype under Th2-polarizing conditions. Clin Exp Allergy 2009;39:89-100.
  38. 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;24:777-92. https://doi.org/10.1080/14728222.2020.1783242
  39. Chan R, Stewart K, Misirovs R, Lipworth BJ. Targeting downstream type 2 cytokines or upstream epithelial alarmins for severe asthma. J Allergy Clin Immunol Pract 2022;10:1497-505.
  40. Hvidtfeldt M, Sverrild A, Pulga A, Frossing L, Silberbrandt A, Hostrup M, et al. Airway hyperresponsiveness reflects corticosteroid-sensitive mast cell involvement across asthma phenotypes. J Allergy Clin Immunol 2023;152:107-16. https://doi.org/10.1016/j.jaci.2023.03.001
  41. Kaur D, Doe C, Woodman L, Heidi Wan WY, Sutcliffe A, Hollins F, et al. Mast cell-airway smooth muscle crosstalk: the role of thymic stromal lymphopoietin. Chest 2012;142:76-85. https://doi.org/10.1378/chest.11-1782
  42. Diver S, Khalfaoui L, Emson C, Wenzel SE, Menzies-Gow A, Wechsler ME, 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;9:1299-312. https://doi.org/10.1016/S2213-2600(21)00226-5
  43. Menzies-Gow A, Corren J, Bourdin A, Chupp G, Israel E, Wechsler ME, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N Engl J Med 2021;384:1800-9. https://doi.org/10.1056/NEJMoa2034975
  44. Kelsen SG, Agache IO, Soong W, Israel E, Chupp GL, Cheung DS, et al. Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: a randomized clinical trial. J Allergy Clin Immunol 2021;148:790-8. https://doi.org/10.1016/j.jaci.2021.03.044
  45. Wechsler ME, Ruddy MK, Pavord ID, Israel E, Rabe KF, Ford LB, et al. Efficacy and safety of itepekimab in patients with moderate-to-severe asthma. N Engl J Med 2021;385:1656-68. https://doi.org/10.1056/NEJMoa2024257
  46. Sze E, Bhalla A, Nair P. Mechanisms and therapeutic strategies for non-T2 asthma. Allergy 2020;75:311-25. https://doi.org/10.1111/all.13985
  47. Lee JH, Wang LC, Yu HH, Lin YT, Yang YH, Chiang BL. Type I IL-1 receptor (IL-1RI) as potential new therapeutic target for bronchial asthma. Mediators Inflamm 2010;2010:567351.
  48. Nakajima H, Hirose K. Role of IL-23 and Th17 cells in airway inflammation in asthma. Immune Netw 2010;10:1-4. https://doi.org/10.4110/in.2010.10.1.1
  49. Saikumar Jayalatha AK, Hesse L, Ketelaar ME, Koppelman GH, Nawijn MC. The central role of IL-33/IL-1RL1 pathway in asthma: from pathogenesis to intervention. Pharmacol Ther 2021;225:107847.
  50. Britt RD Jr, Thompson MA, Sasse S, Pabelick CM, Gerber AN, Prakash YS. Th1 cytokines TNF-α and IFN-γ promote corticosteroid resistance in developing human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 2019;316:L71-81. https://doi.org/10.1152/ajplung.00547.2017
  51. Ahmad S, Mohd Noor N, Engku Nur Syafirah EAR, Irekeola AA, Shueb RH, Chan YY, et al. Anti-tumor necrosis factor for supplementary management in severe asthma: a systematic review and meta-analysis. J Interferon Cytokine Res 2023;43:77-85. https://doi.org/10.1089/jir.2022.0211
  52. Busse WW, Holgate S, Kerwin E, Chon Y, Feng J, Lin J, et al. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma. Am J Respir Crit Care Med 2013;188:1294-302. https://doi.org/10.1164/rccm.201212-2318OC
  53. Liu W, Liu S, Verma M, Zafar I, Good JT, Rollins D, et al. Mechanism of TH2/TH17-predominant and neutrophilic TH2/TH17-low subtypes of asthma. J Allergy Clin Immunol 2017;139:1548-58. https://doi.org/10.1016/j.jaci.2016.08.032
  54. Cosmi L, Liotta F, Maggi E, Romagnani S, Annunziato F. Th17 cells: new players in asthma pathogenesis. Allergy 2011;66:989-98. https://doi.org/10.1111/j.1398-9995.2011.02576.x
  55. Brightling CE, Nair P, Cousins DJ, Louis R, Singh D. Risankizumab in severe asthma: a phase 2a, placebo-controlled trial. N Engl J Med 2021;385:1669-79. https://doi.org/10.1056/NEJMoa2030880
  56. Manka LA, Wechsler ME. Selecting the right biologic for your patients with severe asthma. Ann Allergy Asthma Immunol 2018;121:406-13. https://doi.org/10.1016/j.anai.2018.07.033
  57. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention (2023 Update) [Internet]. Fontana: GINA; 2023 [cited 2023 Dec 1]. Available from: http://www.ginasthma.org.
  58. Menzies-Gow A, Szefler SJ, Busse WW. The relationship of asthma biologics to remission for asthma. J Allergy Clin Immunol Pract 2021;9:1090-8. https://doi.org/10.1016/j.jaip.2020.10.035
  59. Akenroye A, McCormack M, Keet C. Severe asthma in the US population and eligibility for mAb therapy. J Allergy Clin Immunol 2020;145:1295-7. https://doi.org/10.1016/j.jaci.2019.12.009
  60. Papaioannou AI, Fouka E, Papakosta D, Papiris S, Loukides S. Switching between biologics in severe asthma patients: when the first choice is not proven to be the best. Clin Exp Allergy 2021;51:221-7. https://doi.org/10.1111/cea.13809
  61. Chapman KR, Albers FC, Chipps B, Munoz X, Devouassoux G, Bergna M, et al. The clinical benefit of mepolizumab replacing omalizumab in uncontrolled severe eosinophilic asthma. Allergy 2019;74:1716-26. https://doi.org/10.1111/all.13850
  62. Magnan A, Bourdin A, Prazma CM, Albers FC, Price RG, Yancey SW, et al. Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment. Allergy 2016;71:1335-44. https://doi.org/10.1111/all.12914
  63. Scioscia G, Nolasco S, Campisi R, Quarato CMI, Caruso C, Pelaia C, et al. Switching biological therapies in severe asthma. Int J Mol Sci 2023;24:9563.
  64. Menzies-Gow AN, McBrien C, Unni B, Porsbjerg CM, Al-Ahmad M, Ambrose CS, et al. Real world biologic use and switch patterns in severe asthma: data from the International Severe Asthma Registry and the US CHRONICLE Study. J Asthma Allergy 2022;15:63-78.  https://doi.org/10.2147/JAA.S328653