Targeting the Inflammatory Cascade: The Evolution of Monoclonal Antibodies for Severe Asthma Management
DOI:
https://doi.org/10.12775/QS.2026.49.67808Keywords
severe asthma, omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, tezepelumab, astegolimabAbstract
Background: Severe asthma affects approximately 5–10% of the asthma population and is characterized by significant heterogeneity in pathophysiology and clinical presentation. The condition is traditionally categorized into Type 2-high (T2-high) inflammation, driven by mechanisms such as eosinophilia and IgE mediation, and Type 2-low (T2-low) inflammation, which is less well-defined. Standard treatments involving broad immunosuppression with corticosteroids are often insufficient or associated with toxicity in severe cases. Consequently, the understanding of asthma has evolved from a "one-size-fits-all" approach to a precision medicine model based on specific phenotypes and endotypes.
Aim: The aim of this review is to examine the efficacy, safety, and selection of biological therapies for severe asthma.
Materials and Methods: The review included scientific papers sourced from the PubMed and Google Scholar databases.
Results: Monoclonal antibodies have transformed severe asthma management. Omalizumab addresses allergic asthma, while anti-IL-5 agents (mepolizumab, reslizumab, benralizumab) effectively reduce exacerbations in eosinophilic phenotypes. Dupilumab (targeting IL-4/IL-13) offers superior lung function improvement, particularly in mixed phenotypes. Notably, tezepelumab (anti-TSLP) and emerging anti-IL-33 agents demonstrate efficacy across a broader spectrum, offering new therapeutic options for previously refractory T2-low patients.
Conclusions: Biologics have shifted the therapeutic goal from disease control to clinical remission. While T2-high asthma is well-managed by existing targeted therapies, upstream inhibitors now provide vital solutions for the challenging T2-low population. Consequently, a precise, biomarker-driven approach is essential to select the optimal therapy and maximize patient outcomes.
References
1. Bell, M. C., & Busse, W. W. (2013). Severe asthma: an expanding and mounting clinical challenge. The journal of allergy and clinical immunology. In practice, 1(2), 110–122. https://doi.org/10.1016/j.jaip.2013.01.005
2. Farinha, I., & Heaney, L. G. (2024). Barriers to clinical remission in severe asthma. Respiratory research, 25(1), 178. https://doi.org/10.1186/s12931-024-02812-3
3. Chung, K. F., Dixey, P., Abubakar-Waziri, H., Bhavsar, P., Patel, P. H., Guo, S., & Ji, Y. (2022). Characteristics, phenotypes, mechanisms and management of severe asthma. Chinese medical journal, 135(10), 1141–1155. https://doi.org/10.1097/CM9.0000000000001990
4. Chung, K. F., Dixey, P., Abubakar-Waziri, H., Bhavsar, P., Patel, P. H., Guo, S., & Ji, Y. (2022). Characteristics, phenotypes, mechanisms and management of severe asthma. Chinese medical journal, 135(10), 1141–1155. https://doi.org/10.1097/CM9.0000000000001990
5. Rogers, L., Jesenak, M., Bjermer, L., Hanania, N. A., Seys, S. F., & Diamant, Z. (2023). Biologics in severe asthma: A pragmatic approach for choosing the right treatment for the right patient. Respiratory medicine, 218, 107414. https://doi.org/10.1016/j.rmed.2023.107414
6. van Buul, A. R., & Taube, C. (2015). Treatment of severe asthma: entering the era of targeted therapy. Expert opinion on biological therapy, 15(12), 1713–1725. https://doi.org/10.1517/14712598.2015.1084283
7. Zervas, E., Samitas, K., Papaioannou, A. I., Bakakos, P., Loukides, S., & Gaga, M. (2018). An algorithmic approach for the treatment of severe uncontrolled asthma. ERJ open research, 4(1), 00125-2017. https://doi.org/10.1183/23120541.00125-2017
8. Desai, D., Newby, C., Symon, F. A., Haldar, P., Shah, S., Gupta, S., Bafadhel, M., Singapuri, A., Siddiqui, S., Woods, J., Herath, A., Anderson, I. K., Bradding, P., Green, R., Kulkarni, N., Pavord, I., Marshall, R. P., Sousa, A. R., May, R. D., Wardlaw, A. J., … Brightling, C. E. (2013). Elevated sputum interleukin-5 and submucosal eosinophilia in obese individuals with severe asthma. American journal of respiratory and critical care medicine, 188(6), 657–663. https://doi.org/10.1164/rccm.201208-1470OC
9. van Huisstede, A., Rudolphus, A., van Schadewijk, A., Cabezas, M. C., Mannaerts, G. H., Taube, C., Hiemstra, P. S., & Braunstahl, G. J. (2014). Bronchial and systemic inflammation in morbidly obese subjects with asthma: a biopsy study. American journal of respiratory and critical care medicine, 190(8), 951–954. https://doi.org/10.1164/rccm.201407-1225LE
10. McKenzie, A. N. J., Spits, H., & Eberl, G. (2014). Innate lymphoid cells in inflammation and immunity. Immunity, 41(3), 366–374. https://doi.org/10.1016/j.immuni.2014.09.006
11. Pajno, G. B., Castagnoli, R., Arasi, S., Licari, A., Caminiti, L., & Marseglia, G. L. (2020). Pediatric use of omalizumab for allergic asthma. Expert opinion on biological therapy, 20(7), 695–703. https://doi.org/10.1080/14712598.2020.1751115
12. Romano C. (2015). Omalizumab therapy for children and adolescents with severe allergic asthma. Expert review of clinical immunology, 11(12), 1309–1319. https://doi.org/10.1586/1744666X.2015.1083860
13. Humbert, M., Busse, W., Hanania, N. A., Lowe, P. J., Canvin, J., Erpenbeck, V. J., & Holgate, S. (2014). Omalizumab in asthma: an update on recent developments. The journal of allergy and clinical immunology. In practice, 2(5), 525–36.e1. https://doi.org/10.1016/j.jaip.2014.03.010
14. Sattler, C., Garcia, G., & Humbert, M. (2017). Novel targets of omalizumab in asthma. Current opinion in pulmonary medicine, 23(1), 56–61. https://doi.org/10.1097/MCP.0000000000000340
15. Melscoet, L., Khayath, N., Migueres, N., Goltzene, M. A., Meyer, N., & de Blay, F. (2023). Severe non-atopic asthma: omalizumab can reduce severe asthma exacerbations. The Journal of asthma : official journal of the Association for the Care of Asthma, 60(5), 881–889. https://doi.org/10.1080/02770903.2022.2103427
16. Hanania, N. A., Fortis, S., Haselkorn, T., Gupta, S., Mumneh, N., Yoo, B., Holweg, C. T. J., & Chipps, B. E. (2022). Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA. The journal of allergy and clinical immunology. In practice, 10(1), 222–228. https://doi.org/10.1016/j.jaip.2021.08.006
17. Akenroye, A. T., Segal, J. B., Zhou, G., Foer, D., Li, L., Alexander, G. C., Keet, C. A., & Jackson, J. W. (2023). Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation. The Journal of allergy and clinical immunology, 151(5), 1269–1276. https://doi.org/10.1016/j.jaci.2023.01.020
18. Pavord, I. D., Korn, S., Howarth, P., Bleecker, E. R., Buhl, R., Keene, O. N., Ortega, H., & Chanez, P. (2012). Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet (London, England), 380(9842), 651–659. https://doi.org/10.1016/S0140-6736(12)60988-X
19. Israel, E., Canonica, G. W., Brusselle, G., Yang, S., Howarth, P. H., Martin, A. L., Koufopoulou, M., Smith, S. G., & Alfonso-Cristancho, R. (2022). Real-life effectiveness of mepolizumab in severe asthma: a systematic literature review. The Journal of asthma : official journal of the Association for the Care of Asthma, 59(11), 2201–2217. https://doi.org/10.1080/02770903.2021.2008431
20. Liu, M. C., Bagnasco, D., Matucci, A., Pilette, C., Price, R. G., Maxwell, A. C., Alfonso-Cristancho, R., Jakes, R. W., Lee, J. K., & Howarth, P. (2023). Mepolizumab in Patients With Severe Asthma and Comorbidities: 1-Year REALITI-A Analysis. The journal of allergy and clinical immunology. In practice, 11(12), 3650–3661.e3. https://doi.org/10.1016/j.jaip.2023.07.024
21. Nopsopon, T., Lassiter, G., Chen, M. L., Alexander, G. C., Keet, C., Hong, H., & Akenroye, A. (2023). Comparative efficacy of tezepelumab to mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis. The Journal of allergy and clinical immunology, 151(3), 747–755. https://doi.org/10.1016/j.jaci.2022.11.021
22. Pavord, I., Gardiner, F., Heaney, L. G., Domingo, C., Price, R. G., Pullan, A., Oppenheimer, J., Brusselle, G., Nagase, H., Chupp, G., Pizzichini, E., Bañas-Conejero, D., & Howarth, P. (2023). Remission outcomes in severe eosinophilic asthma with mepolizumab therapy: Analysis of the REDES study. Frontiers in immunology, 14, 1150162. https://doi.org/10.3389/fimmu.2023.1150162
23. Pham, T. H., Damera, G., Newbold, P., & Ranade, K. (2016). Reductions in eosinophil biomarkers by benralizumab in patients with asthma. Respiratory medicine, 111, 21–29. https://doi.org/10.1016/j.rmed.2016.01.003
24. Lai, K., Sun, D., Dai, R., Samoro, R., Park, H. S., Åstrand, A., Cohen, D., Jison, M., Shih, V. H., Werkström, V., Yao, Y., Zhang, Y., Zheng, W., Zhong, N., MIRACLE Study Investigators, Principle investigators, Albert, A., Jr, Jianping, B., Bi, C., Lijun, C., … ClinChoice (2024). Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia. Respiratory medicine, 107611. Advance online publication. https://doi.org/10.1016/j.rmed.2024.107611
25. Gauvreau, G. M., Sehmi, R., FitzGerald, J. M., Leigh, R., Cockcroft, D. W., Davis, B. E., Mayers, I., Boulet, L. P., Al-Sajee, D., Salter, B. M., Cusack, R. P., Ho, T., Whetstone, C. E., Alsaji, N., Satia, I., Killian, K. J., Mitchell, P. D., Magee, I. P., Bergeron, C., Bhutani, M., … O'Byrne, P. M. (2024). Benralizumab for allergic asthma: a randomised, double-blind, placebo-controlled trial. The European respiratory journal, 64(3), 2400512. https://doi.org/10.1183/13993003.00512-2024
26. Castro, M., Zangrilli, J., Wechsler, M. E., Bateman, E. D., Brusselle, G. G., Bardin, P., Murphy, K., Maspero, J. F., O'Brien, C., & Korn, S. (2015). Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. The Lancet. Respiratory medicine, 3(5), 355–366. https://doi.org/10.1016/S2213-2600(15)00042-9
27. Harb, H., & Chatila, T. A. (2020). Mechanisms of Dupilumab. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 50(1), 5–14. https://doi.org/10.1111/cea.13491
28. Moran, A., & Pavord, I. D. (2020). Anti-IL-4/IL-13 for the treatment of asthma: the story so far. Expert opinion on biological therapy, 20(3), 283–294. https://doi.org/10.1080/14712598.2020.1714027
29. Castro, M., Corren, J., Pavord, I. D., Maspero, J., Wenzel, S., Rabe, K. F., Busse, W. W., Ford, L., Sher, L., FitzGerald, J. M., Katelaris, C., Tohda, Y., Zhang, B., Staudinger, H., Pirozzi, G., Amin, N., Ruddy, M., Akinlade, B., Khan, A., Chao, J., … Teper, A. (2018). Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. The New England journal of medicine, 378(26), 2486–2496. https://doi.org/10.1056/NEJMoa1804092
30. Zhang, Q., Zhong, N., Dhooria, S., Fu, X., Fang, H., Lin, J., Zhu, S., Laws, E., Wang, Y., Li, V., Hu, C. C., Maloney, J., Abdulai, R. M., & Robinson, L. B. (2025). Dupilumab Efficacy and Safety in Patients With Persistent Asthma: Asia-Pacific Region. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 55(8), 691–700. https://doi.org/10.1111/cea.70005
31. Corren, J., Castro, M., O'Riordan, T., Hanania, N. A., Pavord, I. D., Quirce, S., Chipps, B. E., Wenzel, S. E., Thangavelu, K., Rice, M. S., Harel, S., Jagerschmidt, A., Khan, A. H., Kamat, S., Maroni, J., Rowe, P., Lu, Y., Amin, N., Pirozzi, G., Ruddy, M., … Teper, A. (2020). Dupilumab Efficacy in Patients with Uncontrolled, Moderate-to-Severe Allergic Asthma. The journal of allergy and clinical immunology. In practice, 8(2), 516–526. https://doi.org/10.1016/j.jaip.2019.08.050
32. Rabe, K. F., Nair, P., Brusselle, G., Maspero, J. F., Castro, M., Sher, L., Zhu, H., Hamilton, J. D., Swanson, B. N., Khan, A., Chao, J., Staudinger, H., Pirozzi, G., Antoni, C., Amin, N., Ruddy, M., Akinlade, B., Graham, N. M. H., Stahl, N., Yancopoulos, G. D., … Teper, A. (2018). Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. The New England journal of medicine, 378(26), 2475–2485. https://doi.org/10.1056/NEJMoa1804093
33. Panettieri, R., Jr, Lugogo, N., Corren, J., & Ambrose, C. S. (2024). Tezepelumab for Severe Asthma: One Drug Targeting Multiple Disease Pathways and Patient Types. Journal of asthma and allergy, 17, 219–236. https://doi.org/10.2147/JAA.S342391
34. Caminati, M., Vatrella, A., Rogliani, P., Carpagnano, E., Spanevello, A., & Senna, G. (2024). Tezepelumab for severe asthma: elevating current practice to recognize epithelial driven profiles. Respiratory research, 25(1), 367. https://doi.org/10.1186/s12931-024-02998-6
35. Kurihara, M., Kabata, H., Irie, M., & Fukunaga, K. (2023). Current summary of clinical studies on anti-TSLP antibody, Tezepelumab, in asthma. Allergology international : official journal of the Japanese Society of Allergology, 72(1), 24–30. https://doi.org/10.1016/j.alit.2022.11.006
36. Menzies-Gow, A., Corren, J., Bourdin, A., Chupp, G., Israel, E., Wechsler, M. E., Brightling, C. E., Griffiths, J. M., Hellqvist, Å., Bowen, K., Kaur, P., Almqvist, G., Ponnarambil, S., & Colice, G. (2021). Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. The New England journal of medicine, 384(19), 1800–1809. https://doi.org/10.1056/NEJMoa2034975
37. Corren, J., Menzies-Gow, A., Chupp, G., Israel, E., Korn, S., Cook, B., Ambrose, C. S., Hellqvist, Å., Roseti, S. L., Molfino, N. A., Llanos, J. P., Martin, N., Bowen, K., Griffiths, J. M., Parnes, J. R., & Colice, G. (2023). Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials. American journal of respiratory and critical care medicine, 208(1), 13–24. https://doi.org/10.1164/rccm.202210-2005OC
38. Nordenmark, L. H., Hellqvist, Å., Emson, C., Diver, S., Porsbjerg, C., Griffiths, J. M., Newell, J. D., Peterson, S., Pawlikowska, B., Parnes, J. R., Megally, A., Colice, G., & Brightling, C. E. (2023). Tezepelumab and Mucus Plugs in Patients with Moderate-to-Severe Asthma. NEJM evidence, 2(10), EVIDoa2300135. https://doi.org/10.1056/EVIDoa2300135
39. Corren, J., Parnes, J. R., Wang, L., Mo, M., Roseti, S. L., Griffiths, J. M., & van der Merwe, R. (2017). Tezepelumab in Adults with Uncontrolled Asthma. The New England journal of medicine, 377(10), 936–946. https://doi.org/10.1056/NEJMoa1704064
40. Kelsen, S. G., Agache, I. O., Soong, W., Israel, E., Chupp, G. L., Cheung, D. S., Theess, W., Yang, X., Staton, T. L., Choy, D. F., Fong, A., Dash, A., Dolton, M., Pappu, R., & Brightling, C. E. (2021). Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial. The Journal of allergy and clinical immunology, 148(3), 790–798. https://doi.org/10.1016/j.jaci.2021.03.044
41. Kotani, N., Dolton, M., Svensson, R. J., Ribbing, J., Friberg, L. E., Vadhavkar, S., Cheung, D., Staton, T., Sperinde, G., Jin, J., Putnam, W. S., & Quartino, A. (2022). Population Pharmacokinetics and Exposure-Response Relationships of Astegolimab in Patients With Severe Asthma. Journal of clinical pharmacology, 62(7), 905–917. https://doi.org/10.1002/jcph.2021
42. Calderon, A. A., Dimond, C., Choy, D. F., Pappu, R., Grimbaldeston, M. A., Mohan, D., & Chung, K. F. (2023). Targeting interleukin-33 and thymic stromal lymphopoietin pathways for novel pulmonary therapeutics in asthma and COPD. European respiratory review : an official journal of the European Respiratory Society, 32(167), 220144. https://doi.org/10.1183/16000617.0144-2022
43. Faria, N., Costa, M. I., Fernandes, A. L., Fernandes, A., Fernandes, B., Machado, D. C., Machado, F., Simão, L., Ribeiro, L., Ferreira, L., Boaventura, R., Lima, R., & Ferreira, J. (2025). Biologic Therapies for Severe Asthma: Current Insights and Future Directions. Journal of clinical medicine, 14(9), 3153. https://doi.org/10.3390/jcm14093153
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Emilia Szczerek, Viktoria Płóciniczak
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 7
Number of citations: 0
