Benralizumab: eficacia y seguridad en pacientes con asma grave eosinofílica.



Palabras clave:

benralizumab, asma, eosinófilo, IL-5



El asma grave conlleva una carga de salud desproporcionadamente alta y cerca de la mitad de los adultos con esta patología tiene un fenotipo eosinofílico. En estos pacientes aunado a la producción de eosinófilos en médula ósea, se activan mecanismos de eosinopoyesis local en tejido pulmonar. Benralizumab es un anticuerpo monoclonal humanizado, que se une con alta afinidad y especificidad a la subunidad alfa del receptor de IL-5 (IL-5Rα) sobre la superficie de eosinófilos y otras células. El principal diferenciador de su mecanismo de acción se relaciona con la remoción de un residuo de fucosa en la Fc, lo cual incrementa hasta 50 veces la afinidad a células NK con apoptosis de eosinófilos mediante citotoxicidad celular dependiente de anticuerpos (CCDA), resultando en una reducción rápida y cercana al 100% tanto en suero como en médula ósea. Adicionalmente, benralizumab reduce >90% de los eosinófilos en tejido pulmonar y esputo. En diversos estudios clínicos controlados y en vida real se ha demostrado que esto se traduce en incremento actual del control del asma y disminución del riesgo futuro. El perfil de seguridad es adecuado sin haberse documentado infestaciones parasitarias ni efectos adversos a largo plazo relacionados con la reducción de los eosinófilos.



Severe asthma carries a disproportionately high health burden and about half of adults with this pathology have an eosinophilic phenotype. In these patients, in addition to the production of eosinophils in bone marrow, local eosinopoiesis mechanisms are activated in lung tissue. Benralizumab is a humanized monoclonal antibody, which joins with high affinity and specificity to the alpha subunit of the IL-5 receptor (IL-5Rα) on the surface of eosinophils and other cells. The main differentiator of its mechanism of action is related to the removal of a fucose residue in Fc, which increases up to 50 times the affinity to NK cells with eosinophil apoptosis by antibody-dependent cell cytotoxicity (CCDA), that leads to a direct, rapid and nearly complete depletion in both peripheral blood and bone marrow. Additionally, benralizumab reduces >90% of eosinophils in lung tissue and sputum. Several controlled and real-life clinical studies have shown that this action over eosinophils is related to increased asthma control and decreased future risk. The safety profile is adequate without documenting parasitic infestations or long-term adverse effects related to the reduction of eosinophils.


Dharmage S, Perret J, Custovic A. Epidemiology of asthma in children and adults. Fron Pediat. 2019;7:246. DOI: 10.3389/fped.2019.00246

Dávila-González I, Moreno-Benítez F, Quirce S. Benralizumab: a new approach for the treatment of severe eosinophilic asthma. J Invest Allergol Clin Immunol. 2019; 29(2):84-93. DOI: 10.18176/jiaci.0385

Carr TF, Zeki AA, Kraft M. Eosinophilic and noneosinophilic asthma. Am J Respir Crit Care Med. 2018;197(1):22-37. DOI: 10.1164/rccm.201611-2232PP

Bakakos A, Loukides S, Bakakos P. Severe eosinophilic asthma. J Clin Med. 2019;8(9):1375. DOI: 10.3390/jcm8091375

Jacoby D, Gleich G, Fryer AD. Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. J Clin Invest. 1993;91(4):1314–1318-1318. DOI: 10.1172/JCI116331

Humbles A, Lloyd C, McMillan SJ, Friend DS, Xanthou G, McKenna EE, et al. A critical role for eosinophils in allergic airways remodeling. Science. 2004;305(5691):1776-1779. DOI: 10.1126/science.1100283

Patterson MF, Borish L, Kennedy JL. The past, present, and future of monoclonal antibodies to IL5 eosinophilic asthma: a review. J Asthma Allergy. 2015;8:125-134. DOI: 10.2147/JAA.S74178

Louis R, Lau L, Bron A O. The relationship between airways inflammation and asthma severity. Am J Respir Crit Care Med. 2000;161(1):9-16. DOI: 10.1164/ajrccm.161.1.9802048

Broekema M, Volbeda F, Timens W, Dijkstra A, Lee NA, Postma DS, et al. Airway eosinophilia in remission and progression of asthma: accumulation with a fast decline of FEV(1). Respir Med. 2010;104(9):1254-1262. DOI: 10.1016/j.rmed.2010.03.030

Price DB, Rigazio A, Campbell J, Bleecker ER, Corrigan CJ, Thomas M, et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir Med. 2015;3(11):849-858. DOI: 10.1016/S2213-2600(15)00367-7

Boonpiyathad T, Sözener ZC, Satitsuksanoa P, Akdis CA. Immunologic mechanisms in asthma. Semin Immunol. 2019;46:101333. DOI: 10.1016/j.smim.2019.101333

McBrien C, Menzies-Gow A. The biology of eosinophils and their role in asthma. Front Med (Lausanne). 2017;4:93. DOI: 10.3389/fmed.2017.00093

Molfino N, Kolbeck D, Parker J, Geba GP. Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor. Clin Exp Allergy. 2012;42(5):712-737. DOI: 10.1111/j.1365-2222.2011.03854.x

Bhalla A, Mukherjee M, Nair P. Airway eosinophilopoietic and autoimmune mechanisms of eosinophilia in severe asthma. Immunol Allergy Clin North Am. 2018;38(4):639-654. DOI: 10.1016/j.iac.2018.06.003

Walford HH, Doherty TA. Diagnosis and management of eosinophilic asthma: a US perspective. J Asthma Allergy. 2014:7:53-65. DOI: 10.2147/JAA.S39119

Wagener AH, de Nijs SB, Lutter R, Sousa AR, Bel EH, Sterk PJ, et al. External validation of blood eosinophils, FE(NO) and serum periostin as surrogates for sputum eosinophils in asthma. Thorax. 2015;70(2):115-120. DOI: 10.1136/thoraxjnl-2014-205634

Ortega H, Katz L, Gunsoy N, Keene O, Yancey S. Blood eosinophils counts predict treatment response in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2015;136(3):825-826. DOI: 10.1016/j.jaci.2015.05.039

Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Reed JL, et al. MEDI-563 a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010;125(6):1344-1135. DOI: 10.1016/j.jaci.2010.04.004

Koike M, Kazuyasy N, Akiko F, Iida A, Anazawa H, Takatsu K, et al. Establishment of humanized anti-interleukin-5 receptor alpha chain monoclonal antibodies having a potent neutralizing activity. Hum Antibodies. 2009;18:17-27. DOI: 10.3233/HAB-2009-0198

Sakae Y, Satoh T, Yagi H, Yanaka S, Isoda Y, Iida S, et al. Conformational effects of N-glycan core fucosylation of immunog lobulin G Fc region on its interaction with Fcγ receptor IIIa. Sci Rep. 2017;7:13780. DOI: 10.1038/s41598-017-13845-8

Laviolette M, Gossage DL, Gauvreau G, Leigh R, Katial R, Busse WW, et al. Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia. J Allergy Clin Immunol. 2013;132(5):1086-1096. DOI: 10.1016/j.jaci.2013.05.020

Tuyet-Hang P, Damera G, Newbold P, Ranade K. Reduction in eosinophil biomarkers by benralizumab in patients with asthma. Respir Med. 2016;111:21-29. DOI: 10.1016/j.rmed.2016.01.003

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;2:619-628. DOI: 10.2147/DDDT.S155307

Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. Efficacy and safety of benralizmumab for patients with severe asthma uncontrolled with high-dosage inhaled corticoesteroids and long-acting β2 – agonist (SIROCCO): a randomized, multicenter, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115-2127. DOI: 10.1016/S0140-6736(16)31324-1

FitzGerald J, Bleecker E, Nair P, Korn S, Ohta K, Busse WW, et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2128-2141. DOI: 10.1016/S0140-6736(16)31322-8

Nair P, Wenzel S, Rabe K. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017;376:2448-2458. DOI: 10.1056/NEJMoa1703501

Jackson DJ, Humbert M, Hirsch I, Newbold P, Garcia-Gil E. Ability of serum IgE concentration to predict exacerbation risk and benralizumab efficacy for patients with severe eosinophilic asthma. Adv Ther. 2020;37(2):718-729. DOI: 10.1007/s12325-019-01191-2

FitzGeral JM, Bleecker EM, Menzies-Gow A, Zangrilli JG, Hirsch I, Metcalfe P, et al. Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies. Lancet Respir Med. 2018;6(1):51-64. DOI: 10.1016/S2213-2600(17)30344-2

Bleecker E, Wechsler M, FitzGerarld M, Menzies-Gow A, Wu Y, Hirsch I, et al. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018;52(4):1800936. DOI: 10.1183/13993003.00936-2018

Harrison T W, Chanez P, Menzella F. Exacerbation reduction and early and sustained improvements in SGRQ, lung function, and symptoms of nasal polyposis with benralizumab for severe, eosinophilic asthma: phase IIIb ANDHI trial. Am J Respir Crit Care Med. 2020;201:A4274. DOI: 10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A4274

Menzies-Gow A, Corren J, Bel E, Maspero J, Gurnell M, Wessman P, et al. Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial. ERJ Open Res. 2019;5(3):00009-2019. DOI: 10.1183/23120541.00009-2019

Jackson D, Kent B D, Humbert M et al. Enabling reductions in maintenance ICS/LABA therapy using as needed anti-inflammatory reliever for patients with severe eosinophilic asthma controlled with benralizumab: SHAMAL phase IV clinical study. Am J Respir Crit Care Med. 2020;201:A3020. DOI: 10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A3020

Busse W, Bleecker E, FitzGerald J M, et al. Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial. Lancet Respir Med. 2019;7(1):46-59. DOI: 10.1016/S2213-2600(18)30406-5

A safety extension study with benralizumab for asthmatic adults on inhaled corticosteroid plus long-acting β2 agonist (MELTEMI). NCT02808819.

Zeitlin P, Leong M, Cole J, Mallory RM, Shih VH, Olsson RF, et al. Benralizumab does not impair antibody response to seasonal influenza vaccination in adolescent and young adult patients with moderate to severe asthma: results from the Phase IIIb ALIZE trial. J Asthma Allergy. 2018;11:181-192. DOI: 10.2147/JAA.S172338

Likura M, Tsukada A, Hirashima J et al. The clinical effectiveness and safety of benralizumab for Japanese patients with severe asthma. Am J Respir Crit Care Med. 2019;199:A1312. DOI: 10.1164/ajrccm-conference.2019.199.1_MeetingAbstracts.A1312

Izumo T, Tone M, Kuse N, Awano N, Tanaka A, Jo T, et al. Effectiveness and safety of benralizumab for severe asthma in clinical practice (J-BEST): a prospective study. Ann Transl Med. 2020;8(7):438. DOI: 10.21037/atm.2020.04.01

Pelaia C, Busceti MT, Vatrella A, Rago GF, Crimi C, Pelaia G, et al. Real-life of benralizumab effects in patients with severe allergic eosinophilic asthma: assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after first drug dose. Pulm Pharmacol Ther. 2019;58:1-5. DOI: 10.1016/j.pupt.2019.101830

Panettieri RA, Welte T, Shenoy K, Korn S, Jandl M, Kerwin EM, et al. Onset of effect, changes in airflow obstruction and lung volume, and health-related quality of life improvements with benralizumab for patients with severe eosinophilic asthma: phase IIIb randomized, controlled trial (SOLANA). J Asthma Allergy. 2020;13:115-126. DOI: 10.2147/JAA.S240044

Kavanagh J, Roxas C, Thomson L, et al. P89 real-world 1 year effectiveness of benralizumab in severe eosinophilc asthma. Thorax. 2019;74(Suppl 2):A1-A262. DOI: 10.1136/thorax-2019-BTSabstracts2019.232

Jackson D, Dube S, Morris T. Improvement of clinical outcomes in severe eosinophilic asthma patients treated with benralizumab in real-world clinical practice in England: XALOC Study Programme. Am J Respir Crit Care Med. 2020;201:A3028. DOI: 10.1164/ajrccm-conference.2020.201.1_MeetingAbstracts.A3028

d´Ancona G, Bains S, Green L et al. P86 does adherence to ICS/LABA therapy change following initiation of benralizumab in the treatment of severe asthma and does this affect outcome? Thorax. 2019;74(Suppl 2):A1-A262. DOI: 10.1136/thorax-2019-BTSabstracts2019.229

Mavissakalian M, Brady S. The current state of biologic therapies for treatment of refractory asthma. Clin Rev Allergy Immunol. 2020;59(2):195-207. DOI: 10.1007/s12016-020-08776-8.

de Groot J, Ten Brinke A, Bel E. Management of the patient with eosinophilic asthma: a new era begins. ERJ Open Res. 2015;1(1):00024-2015. DOI: 10.1183/23120541.00024-2015

Información para Prescribir Ampliada – Fasenra. AstraZeneca Mexico 2018.

Rose DM, Hrncir DE. Primary eosinophilic lung diseases. Allergy Asthma Proc. 2013;34(1):19-25. DOI: 10.2500/aap.2013.34.3628

Ramirez GA, Yacoub MR, Ripa M, Mannina D, Cariddi A, Ciceri F, et al. Eosinophils from physiology to disease: a comprehensive review. Biomed Res Int. 2018;2018:9095275. DOI: 10.1155/2018/9095275

Long H, Zhang G, Wang L, Lu Q. Eosinophilic skin diseases: a comprehensive review. Clin Rev Allergy Immunol. 2016;50(2):189-213. DOI: 10.1007/s12016-015-8485-8

Ramakrishnan S, Camp JR, Vijayakumar B, et al. The use of benralizumab in the treatment of near-fatal asthma: a new approach. Am J Respir Crit Care Med. 2020;201(11):1441-1443. DOI: 10.1164/rccm.202001-0093LE

Ferguson GT, Cole J, Aurivillius M, Roussel P, Barker P, Martin BJ, et al. Single-use autoinjector functionality and reliability for at-home administration of benralizumab for patients with severe asthma: GRECO trial results. J Asthma Allergy. 2019;12:363-373. DOI: 10.2147/JAA.S224266

Ferguson G, Mansur A, Jacobs J, Hebert J, Clawson C, Tao W, et al. Assessment of an accessorized pre-filled syringe for home-administered benralizumab in severe asthma. J Asthma Allergy. 2018;11:63-72. DOI: 10.2147/JAA.S157762.

Martin UJ, Fuhr R, Forte P, Barker P, Axley MJ, Yan L, et al. Comparison of autoinjector with accessorized prefilled syringe for benralizumab pharmacokinetic exposure: AMES trial results. J Asthma. 2019;1-9. DOI: 10.1080/02770903.2019.1663428

Benralizumab for treating severe eosinophilic asthma. EE. UU.: National Institute for Health and Care Excellence; 2019.

GINA difficult-to-treat and severe asthma in adolescent and adult patients. Diagnosis and management. EE. UU.: Global Initiative for Asthma; 2019. Disponible en:

Custovic A, Johnston SL, Pavord I, Gaga M, Fabbri L, Bel EH, et al. EAACI position statement on asthma exacerbations and severe asthma. Allergy. 2013;68(12):1520-1531. DOI: 10.1111/all.12275

Mukherjee M, Bakakos P, Loukides S. New paradigm in asthma management: switching between biologics! Allergy. 2020;75(4):743-745. DOI: 10.1111/all.14038.

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