Overlapping Effects of New Monoclonal Antibodies for Severe Asthma

Overview

Journal Drugs

Specialty Pharmacology

Date 2017 Sep 27

PMID 28948572

Citations 16

Authors

Christian Domingo

Affiliations

Soon will be listed here.

Abstract

Among the monoclonal antibodies (mAbs) developed for severe asthma treatment, three have already been marketed. Omalizumab was the first, more than 10 years ago; today, mepolizumab and reslizumab are also available in the European Union and the US. Omalizumab blocks free immunoglobulin E (IgE), mepolizumab and reslizumab block an interleukin (IL-5). In the near future, dupilumab and benralizumab are expected to emerge as two new alternatives. Benralizumab blocks the receptor for IL-5 (IL5-Rα) and has a direct cytotoxic effect on eosinophils, and dupilumab blocks the α-unit of the heterodimeric receptor for IL-4 and IL-13 (IL-4Rα); as a result, dupilumab can block both IL-4 and IL-13. The purpose of this manuscript is to present the pathophysiology of some immunological aspects of severe asthma, describe the adaptive and innate immunity arms as well as their interrelations (stressing the subordination of the adaptive arm to the innate arm), outline the pharmacologic effects of these mAbs, clarify the overlapping effects of the different mAbs, and discuss the differences between mAbs based on their target molecules. Based on the data presented, I propose omalizumab for patients with an allergic phenotype regardless of their peripheral eosinophilic count, and anti-IL-5 as an alternative in allergic patients with blood eosinophilia in which omalizumab has failed; anti-IL5 for patients with an eosinophilic phenotype and omalizumab as an alternative in patients in whom anti-IL5 fails and IgE ≥30 IU/mL (compassionate use). Omalizumab is also proposed for patients with severe chronic asthma allergic to seasonal allergens.

Citing Articles

Long-term multicenter comparison shows equivalent efficacy of monoclonal antibodies in severe asthma therapy.

Kayser M, Suhling H, Fuge J, Hinze C, Drick N, Kneidinger N BMC Pulm Med. 2024; 24(1):149.

PMID: 38515071 PMC: 10956233. DOI: 10.1186/s12890-024-02964-4.

The Incredible Adventure of Omalizumab.

Domingo C, Monserrate D, Sogo A, Mirapeix R Int J Mol Sci. 2024; 25(5).

PMID: 38474304 PMC: 10932234. DOI: 10.3390/ijms25053056.

Exploring redox imbalance and inflammation for asthma therapy.

Barnabas M, Awakan O, Rotimi D, Akanji M, Adeyemi O Mol Biol Rep. 2023; 50(9):7851-7865.

PMID: 37517067 DOI: 10.1007/s11033-023-08688-8.

Efficacy and Potential Positioning of Tezepelumab in the Treatment of Severe Asthma.

Plaza V, Canete C, Domingo C, Martinez Rivera C, Munoz X Open Respir Arch. 2023; 5(2):100231.

PMID: 37496871 PMC: 10369521. DOI: 10.1016/j.opresp.2022.100231.

[Consensus document for severe asthma in adults. 2022 update].

Alvarez-Gutierrez F, Blanco-Aparicio M, Casas-Maldonado F, Plaza V, Gonzalez-Barcala F, Carretero-Gracia J Open Respir Arch. 2023; 4(3):100192.

PMID: 37496585 PMC: 10369632. DOI: 10.1016/j.opresp.2022.100192.

References

Braunstahl G, Chen C, 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):1141-51. DOI: 10.1016/j.rmed.2013.04.017. View

Bel E, Wenzel S, Thompson P, Prazma C, Keene O, Yancey S . Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014; 371(13):1189-97. DOI: 10.1056/NEJMoa1403291. View

Buhl R, Humbert M, Bjermer L, Chanez P, Heaney L, Pavord I . Severe eosinophilic asthma: a roadmap to consensus. Eur Respir J. 2017; 49(5). DOI: 10.1183/13993003.00634-2017. View

Pelaia G, Vatrella A, Busceti M, Gallelli L, Preiano M, Lombardo N . Role of biologics in severe eosinophilic asthma - focus on reslizumab. Ther Clin Risk Manag. 2016; 12:1075-82. PMC: 4936812. DOI: 10.2147/TCRM.S111862. View

Imaoka H, Campbell H, Babirad I, Watson R, Mistry M, Sehmi R . TPI ASM8 reduces eosinophil progenitors in sputum after allergen challenge. Clin Exp Allergy. 2011; 41(12):1740-6. DOI: 10.1111/j.1365-2222.2011.03816.x. View

Rosenberg H, Phipps S, Foster P . Eosinophil trafficking in allergy and asthma. J Allergy Clin Immunol. 2007; 119(6):1303-10. DOI: 10.1016/j.jaci.2007.03.048. View

Nakajima H, Gleich G, Kita H . Constitutive production of IL-4 and IL-10 and stimulated production of IL-8 by normal peripheral blood eosinophils. J Immunol. 1996; 156(12):4859-66. View

Le H, Kim W, Kim J, Cho H, Kwon B . Interleukin-33: a mediator of inflammation targeting hematopoietic stem and progenitor cells and their progenies. Front Immunol. 2013; 4:104. PMC: 3644799. DOI: 10.3389/fimmu.2013.00104. View

Zhao L, Lotvall J, Linden A, Tomaki M, Sjostrand M, Bossios A . Prolonged eosinophil production after allergen exposure in IFN-gammaR KO mice is IL-5 dependent. Scand J Immunol. 2008; 67(5):480-8. DOI: 10.1111/j.1365-3083.2008.02098.x. View

10.

Sehmi R, Smith S, Kjarsgaard M, Radford K, Boulet L, Lemiere C . Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone-dependent severe asthma. Clin Exp Allergy. 2015; 46(6):793-802. DOI: 10.1111/cea.12695. View

11.

Pennington L, Tarchevskaya S, Brigger D, Sathiyamoorthy K, Graham M, Nadeau K . Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange. Nat Commun. 2016; 7:11610. PMC: 4873975. DOI: 10.1038/ncomms11610. View

12.

Cazzola M, Camiciottoli G, Bonavia M, Gulotta C, Ravazzi A, Alessandrini A . Italian real-life experience of omalizumab. Respir Med. 2010; 104(10):1410-6. DOI: 10.1016/j.rmed.2010.04.013. View

13.

Hogan S, Rosenberg H, Moqbel R, Phipps S, Foster P, Lacy P . Eosinophils: biological properties and role in health and disease. Clin Exp Allergy. 2008; 38(5):709-50. DOI: 10.1111/j.1365-2222.2008.02958.x. View

14.

Schumann C, Kropf C, Wibmer T, Rudiger S, Stoiber K, Thielen A . Omalizumab in patients with severe asthma: the XCLUSIVE study. Clin Respir J. 2011; 6(4):215-27. DOI: 10.1111/j.1752-699X.2011.00263.x. View

15.

Yagami A, Orihara K, Morita H, Futamura K, Hashimoto N, Matsumoto K . IL-33 mediates inflammatory responses in human lung tissue cells. J Immunol. 2010; 185(10):5743-50. DOI: 10.4049/jimmunol.0903818. View

16.

Mukai K, Matsuoka K, Taya C, Suzuki H, Yokozeki H, Nishioka K . Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells. Immunity. 2005; 23(2):191-202. DOI: 10.1016/j.immuni.2005.06.011. View

17.

Wang Y, Ito T, Wang Y, Homey B, Watanabe N, Martin R . Maintenance and polarization of human TH2 central memory T cells by thymic stromal lymphopoietin-activated dendritic cells. Immunity. 2006; 24(6):827-838. DOI: 10.1016/j.immuni.2006.03.019. View

18.

Vennera M, Perez de Llano L, Bardagi S, Ausin P, Sanjuas C, Gonzalez H . Omalizumab therapy in severe asthma: experience from the Spanish registry--some new approaches. J Asthma. 2012; 49(4):416-22. DOI: 10.3109/02770903.2012.668255. View

19.

Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B . 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. Lancet. 2016; 388(10039):31-44. DOI: 10.1016/S0140-6736(16)30307-5. View

20.

Bleecker E, FitzGerald J, Chanez P, Papi A, Weinstein S, Barker P . Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016; 388(10056):2115-2127. DOI: 10.1016/S0140-6736(16)31324-1. View