Use and results of astegolimab in the management of severe asthma: what is known?
DOI:
https://doi.org/10.24265/horizmed.2023.v23n1.13Keywords:
asthma, drug therapy, treatment outcome, review literature as topicAbstract
Asthma is a chronic inflammatory disease of the respiratory tract which causes high health costs, substantially affects the quality of life and, depending on certain associated risk factors, reduces the functional capacity of the sufferer. By 2019, asthma affected 262 million people (4.3 % of the world’s population) and caused 461,000 deaths. It is estimated that there
will be an additional 100 million people with asthma by 2025. Severe asthma is a phenotype resistant to corticosteroids which causes a greater number of exacerbations and substantially affects the quality of life and functional capacity of the affected person. Its management was initially aimed at suppressing the symptoms and then evolved to understand, although not completely, the intrinsic systems of its generation. Thus, new ways of influencing its management have been studied by modulating the immune response and the inflammatory cascade with the generation of biological drugs. As a result of the study and identification of various endotypes and phenotypes, drugs with different mechanisms of action have been designed and have demonstrated to be considerably useful in recent years. However, there is evidence that resistance even to these drugs has occurred, being necessary to continue researching new therapeutic targets. Astegolimab is a novel human IgG2 monoclonal antibody that blocks IL-33 signaling by targeting ST2, its receptor, thus controlling the inflammatory response in severe asthma. A phase 2b clinical trial is currently undergoing, although previous results have found positive and significant results regarding immunomodulation, pulmonary function, symptomatology and quality of life. At present, there is almost no literature that has analyzed the potential of astegolimab in severe asthma, and practically only trials that have evaluated it and some reviews that have shared its pharmacokinetics and pharmacodynamics are available. Based on the above, the aim of this review is to synthesize evidence related to the results of the use of astegolimab in
severe asthma and discuss epidemiological and pathophysiological aspects that highlight the need for the development of a safe, effective and efficient drug.
Downloads
References
Mims JW. Asthma: Definitions and pathophysiology. Int Forum Allergy Rhinol. 2015;5(Suppl. 1):S2-6.
Boulet LP, Fitzgerald JM, Reddel HK. The revised 2014 GINA strategy report: opportunities for change. Curr Opin Pulm Med. 2015;21(1):1-7.
Yamasaki A, Okazaki R, Harada T. Neutrophils and asthma. Diagnostics (Basel). 2022;12(5):1175.
Abul MH, Phipatanakul W. Severe asthma in children: Evaluation and management. Allergol Int. 2019;68(2):150-7.
Cote A, Godbout K, Boulet L The management of severe asthma in 2020. Biochem Pharmacol. 2020;179:114112.
Kaur R, Chupp G. Phenotypes and endotypes of adult asthma: Moving toward precision medicine. J Allergy Clin Immunol. 2019; 144(1):1-12.
Wu TD, Brigham EP, McCormack MC. Asthma in the Primary Care Setting. Med Clin North Am. 2019;103(3):435-52.
Ntontsi P, Photiades A, Zervas E, Xanthou G, Samitas K. Genetics and epigenetics in asthma. Int J Mol Sci. 2021;22(5):2412.
Sockrider M, Fussner L. What is asthma? Am J Respir Crit Care Med. 2020;202(9):p25-6.
Chung KF, Dixey P, Abubakar-Waziri H, Bhavsar P, Patel PH, Guo S, et al. Characteristics, phenotypes, mechanisms and management of severe asthma. Chin Med J. 2022;135(10):1141-55.
Jones TL, Neville DM, Chauhan AJ. Diagnosis and treatment of severe asthma: a phenotype-based approach. Clin Med (Lond). 2018;18(Suppl. 2):36-40.
Schoettler N, Strek ME. Recent advances in severe asthma: from phenotypes to personalized medicine. Chest. 2020;157(3):516-28.
Chung KF. Clinical management of severe therapy-resistant asthma. Expert Rev Respir Med. 2017;11(5):395-402.
Kardas G, Kuna P, Panek M. Biological therapies of severe asthma and their possible effects on airway remodeling. Front Immunol. 2020;11:1134.
Pelaia C, Pelaia G, Crimi C, Maglio A, Stanziola AA, Calabrese C, et al. Novel biological therapies for severe asthma endotypes. Biomedicines. 2022;10(5):1064.
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(3):790-8.
Kotani N, Dolton M, Svensson RJ, Ribbing J, Friberg LE, Vadhavkar S, et al. Population pharmacokinetics and exposure-response relationships of astegolimab in patients with severe asthma. J Clin Pharmacol. 2022;62(7):905-17.
Yousuf AJ, Mohammed S, Carr L, Yavari M, Micieli C, Mistry V, et al. Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease (COPD-ST2OP): A phase 2a, placebo-controlled trial. Lancet Respir Med. 2022;10(5):469-77.
Svensson RJ, Ribbing J, Kotani N, Dolton M, Vadhavkar S, Cheung D, et al. Population repeated time-to-event analysis of exacerbations in asthma patients: A novel approach for predicting asthma exacerbations based on biomarkers, spirometry, and diaries/questionnaires. CPT Pharmacometrics Syst Pharmacol. 2021;10(10):1221-35.
World Health Organization. Asthma [Internet]. Geneva:WHO. 2022. Disponible en: https://www.who.int/es/news-room/fact-sheets/detail/asthma
Loftus PA, Wise SK. Epidemiology of asthma. Curr Opin Otolaryngol Head Neck Surg. 2016;24(3):245-9.
Braman SS. The global burden of asthma. Chest. 2006;130(Suppl. 1):4S-12S.
Asher MI, Rutter CE, Bissell K, Chiang C, Sony AE, et al. Worldwide trends in the burden of asthma symptoms in school-aged children: Global Asthma Network Phase I cross-sectional study. Lancet. 2022;398(10311):1569-80.
Mushtaq A. Asthma in the USA: the good, the bad, and the disparity. Lancet Respir Med. 2018;6(5):335-6.
Flores C, Ma S, Pino-Yanes M, Wade MS, Perez-Mendez L, Kittles RA, et al. African ancestry is associated with asthma risk in African Americans. PLoS One. 2012;7(1):e26807.
Ronnebjerg L, Axelsson M, Kankaanranta H, Backman H, Radinger M, Lundback B, et al. Severe asthma in a general population study: Prevalence and clinical characteristics. J Asthma Allergy. 2021;14:1105-15.
Lai AKW, Beasley R, Crane J, Foliaki S, Shah J, Weiland S, et al. Global variation in the prevalence and severity of asthma symptoms: phase three of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax. 2009;64(6):476-83.
Dharmage SC, Perret JL, Custovic A. Epidemiology of asthma in children and adults. Front Pediatr. 2019;7:246.
Chen S, Golam S, Myers J, Bly C, Smolen H, Xu X. Systematic literature review of the clinical, humanistic, and economic burden associated with asthma uncontrolled by GINA Steps 4 or 5 treatment. Curr Med Res Opin. 2018;34(12):2075-88.
Dennis RJ, Caraballo L, Garcia E, Rojas MX, Rondon MA, Perez A, et al. Prevalence of asthma and other allergic conditions in Colombia 2009-2010: a cross-sectional study. BMC Pulm Med. 2012;12:17.
Bunyavanich S, Schadt EE. Systems biology of asthma and allergic diseases: A multiscale approach. J Allergy Clin Immunol. 2015;135(1):31-42.
Gautam Y, Afanador Y, Ghandikota S, Mersha TB. Comprehensive functional annotation of susceptibility variants associated with asthma. Hum Genet. 2020;139(8):1037-53.
Namjou B, Lape M, Malolepsza E, DeVore SB, Weirauch MT, Dikilitas O, et al. Multiancestral polygenic risk score for pediatric asthma. J Allergy Clin Immunol. 2022;S0091-6749(22)00660-1.
Martinez FD, Vercelli D. Asthma. Lancet. 2013; 382(9901): 1360-72.
Singh PB, Pua HH, Happ HC, Schneider C, Moltke J, Locksley RM, et al. MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation. J Exp Med. 2017;214(12):3627-43.
Lovinsky-Desir S, Miller RL. Epigenetics, asthma, and allergic diseases: A review of the latest advancements. Curr Allergy Asthma Rep. 2012;12(3):211-20.
Raissy H, Blake K. Vitamin D and asthma: Association, causality, or intervention? Pediatr Allergy Immunol Pulmonol. 2015;28(1):60-2.
Wong KO, Hunter B, Douwes J, Senthilselvan A. Asthma and wheezing are associated with depression and anxiety in adults: An analysis from 54 countries. Pulm Med. 2013;2013:929028.
Kuruvilla ME, Lee FEH, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219-33.
Barnes KC. Genetic studies of the etiology of asthma. Proc Am Thorac Soc. 2011;8(2):143-8.
Schmiedel BJ, Seumois G, Samaniego-Castruita D, Cayford J, Schulten V, Chavez L, et al. 17q21 asthma-risk variants switch CTCF binding and regulate IL-2 production by T cells. Nat Commun. 2016;7:13426.
Bullone M, Carriero V, Bertolini F, Ricciardolo FLM. Effect of bronchial neutrophilia on airway remodeling in asthma. Eur Respir J. 2019;54(Suppl. 63):3864.
Fahy JV. Type 2 inflammation in asthma-present in most, absent in many. Nat Rev Immunol. 2015;15(1):57-65.
Oliphant CJ, Barlow JL, Mckenzie ANJ. Insights into the initiation of type 2 immune responses. Immunology. 2011;134(4):378-85.
Motomura Y, Kitamura H, Hijikata A, Matsunaga Y, Matsumoto K, Inoue H, et al. The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells. Nat Immunol. 2011;12(5):450-9.
Lu Y, Kared H, Tan SW, Becht E, Newell EW, Van Bever HPS, et al. Dynamics of helper CD4 T cells during acute and stable allergic asthma. Mucosal Immunol. 2018;11(6):1640-52.
Pavord ID, Korn E, 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(9842):651-9.
Ortega HG, Yancey SW, Mayer B, Gunsoy NB, Keene ON, Bleecker ER, et al. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies. Lancet Respir Med. 2016;4(7):549-56.
Haldar P, Pavord ID. Noneosinophilic asthma: A distinct clinical and pathologic phenotype. J Allergy Clin Immunol. 2007;119(5):1043-52.
Pike KC, Levy ML, Moreiras J, Fleming L. Managing problematic severe asthma: beyond the guidelines. Arch Dis Child. 2018;103(4):392-7.
Lazarus SC, Krishnan JA, King TS, Lang JE, Blake KV, Covar R, et al. Mometasone or tiotropium in mild asthma with a low sputum eosinophil level. N Engl J Med. 2019;380(21):2009-19.
Papadopoulos NG, Barnes P, Canonica GW, Gaga M, Heaney L, Menzies-Gow A, et al. The evolving algorithm of biological selection in severe asthma. Allergy. 2020;75(7):1555-63.
Normansell R, Walker S, Milan SJ, Walters EH, Nair P. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;2014(1):CD003559.
Pelaia C, Vatrella A, Busceti MT, Gallelli L, Terracciano R, Savino R, et al. Severe eosinophilic asthma: From the pathogenic role of interleukin-5 to the therapeutic action of mepolizumab. Drug Des Devel Ther. 2017;11:3137-44.
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;12:619-28.
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 b2-agonists (SIROCCO): A randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-27.
Pelaia C, Vatrella A, Gallelli L, Terracciano R, Navalesi P, Maselli R, et al. Dupilumab for the treatment of asthma. Expert Opin Biol Ther. 2017;17(12):1565-72.
Liew FY, Girard J, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immunol. 2016;16(11):676-89.
Corren J, Pham T, Garcia E, Salapa K, Ren P, Parnes JR, et al. Baseline type 2 biomarker levels and response to tezepelumab in severe asthma. Allergy. 2022;77(6):1786-96.
Hoffmann-La Roche. A Study to Assess the Efficacy and Safety of MSTT1041A in Participants With Uncontrolled Severe Asthma [Internet]. ClinicalTrials.gov; 2022 [citado el 14 de febrero de 2023]. Report No.: NCT02918019. Disponible en: https://clinicaltrials.gov/ct2/show/NCT02918019
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Horizonte Médico (Lima)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Horizonte Médico (Lima) (Horiz. Med.) journal’s research outputs are published free of charge and are freely available to download under the open access model, aimed at disseminating works and experiences developed in biomedical and public health areas, both nationally and internationally, and promoting research in the different fields of human medicine. All manuscripts accepted and published in the journal are distributed free of charge under the terms of a Creative Commons license – Attribution 4.0 International (CC BY 4.0).
