Bloqueo de inmunoglobulina E en el asma grave

Autores/as

DOI:

https://doi.org/10.29262/ram.v67i7.777

Palabras clave:

Asma grave, Bloqueo de inmunoglobulina E, Interferón, Omalizumab

Resumen

El asma es una enfermedad inflamatoria crónica y heterogénea que afecta las vías respiratorias inferiores tanto de niños como de adultos. Los pacientes en quienes se han abordado factores modificables y continúan con episodios graves de asma aún después de la aplicación de dosis altas de corticosteroides se les diagnostica con asma grave; esta se asocia con mayor mortalidad y hospitalizaciones, así como con menor calidad de vida y mayores costos de atención médica. Se han identificado mecanismos inmunoinflamatorios tipo 2 altos, bajos y mixtos, en los cuales la inmunoglobulina E es un biomarcador prominente para el asma de inicio temprano y el asma de inicio tardío no alérgico. El bloqueo de la inmunoglobulina E disminuye indirectamente la expresión de su receptor de alta afinidad, disminuyendo la producción de citocinas tipo 2 e inhibiendo la inflamación eosinofílica, así como la modulación de la inflamación tipo 2. Por otro lado, la evidencia preclínica y clínica respalda la existencia de una estrecha contrarregulación de las vías del receptor de inmunoglobulina E de alta afinidad y del interferón, y un posible mecanismo de prevención de exacerbaciones inducidas por virus. La siguiente revisión resume la larga experiencia clínica del resultado de bloquear la inmunoglobulina E en el asma grave.   

Citas

Dharmage SC, Perret JL, Custovic A. Epidemiology of asthma in children and adults. Front Pediatr. 2019;7:246. DOI: 10.3389/fped.2019.00246

Masoli M, Fabian D, Holt S, Beasley R, Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 2004;59(5):469-478. DOI: 10.1111/j.1398-9995.2004.00526.x

To T, Stanojevic S, Moores G, et al. Global asthma prevalence in adults: findings from the cross-sectional world health survey. BMC Public Health. 2012;12:204. DOI: 10.1186/1471-2458-12-204

Lötvall J, Akdis CA, Bacharier LB, Bjermer L, Casale TB, Custovic A, et al. Asthma endotypes: a new approach to classification of disease entities within the asthma syndrome. J Allergy Clin Immunol. 2011;127(2):355-360. DOI: 10.1016/j.jaci.2010.11.037

Thien F, Beggs PJ, Csutoros D, Darvall J, Hew M, Davies JM, et al. The Melbourne epidemic thunderstorm asthma event 2016: an investigation of environmental triggers, effect on health services, and patient risk factors. Lancet Planet Health. 2018;2(6):e255-e263. DOI: 10.1016/S2542-5196(18)30120-7

Achakulwisut P, Brauer M, Hystad P, Anenberg SC. Global, national, and urban burdens of paediatric asthma incidence attributable to ambient NO2 pollution: estimates from global datasets. Lancet Planet Health. 2019;3(4):e166-e178. DOI: 10.1016/S2542-5196(19)30046-4

Kim CK, Callaway Z, Gern JE. Viral infections and associated factors that promote acute exacerbations of asthma. Allergy Asthma Immunol Res. 2018;10:12-17. DOI: 10.4168/aair.2018.10.1.12

Custovic A, Belgrave D, Lin L, Bakhsoliani E, Telcian AG, Solari R, et al. Cytokine responses to rhinovirus and development of asthma, allergic sensitization, and respiratory infections during childhood. Am J Respir Crit Care Med. 2018;197(10):1265-1274. DOI: 10.1164/rccm.201708-1762OC

Helby J, Nordestgaard BG, Benfield T, Bojesen SE. Asthma, other atopic conditions and risk of infections in 105 519 general population never and ever smokers. J Intern Med. 2017;282(3):254-267. DOI: 10.1111/joim.12635

Custovic A, Ainsworth J, Arshad H, et al. The Study Team for Early Life Asthma Research (STELAR) consortium ‘Asthma e-lab’: team science bringing data, methods and investigators together. Thorax. 2015;70(8):799-801. DOI: 10.1136/thoraxjnl-2015-206781

Ebmeier S, Thayabaran D, Braithwaite I, Bénamara C, Weatherall M, Beasley R. Trends in international asthma mortality: analysis of data from the WHO Mortality Database from 46 countries (1993-2012). Lancet. 2017;390(10098):935-945. DOI: 10.1016/S0140-6736(17)31448-4

Global Strategy for Asthma Management and Prevention, 2019. EE. UU.: Global Initiative for Asthma; 2019.

Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43(2):343-373. DOI: 10.1183/09031936.00202013. Errata en: Eur Respir J. 2014;43(4):1216. Correción del autor en: Eur Respir J. 2018;52(1):1352020.

Rajan S, Gogtay NJ, Konwar M, Thatte UM. The global initiative for asthma guidelines (2019): change in the recommendation for the management of mild asthma based on the SYGMA-2 trial - A critical appraisal. Lung India. 2020;37(2):169-173. DOI: 10.4103/lungindia.lungindia_308_19

Reddel HK, Taylor DR, Bateman ED, Boulet LP, Boushey HA, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180(1):59-99. DOI: 10.1164/rccm.200801-060ST

Hekking PP, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135(4):896-902. DOI: 10.1016/j.jaci.2014.08.042

Zervas E, Samitas K, Papaioannou AI, Bakakos P, Loukides S, Gaga M. An algorithmic approach for the treatment of severe uncontrolled asthma. ERJ Open Res. 2018;4(1):125-2017. DOI: 10.1183/23120541.00125-2017

Chung KF, Adcock IM. Precision medicine for the discovery of treatable mechanisms in severe asthma. Allergy. 2019;74(9):1649-1659. DOI: 10.1111/all.13771

Narendra D, Blixt J, Hanania NA. Immunological biomarkers in severe asthma. Semin Immunol. 2019;46:101332. DOI: 10.1016/j.smim.2019.101332

Lambrecht BN, Hammad H. The immunology of asthma. Nat Immunol. 2015;16(1):45-56. DOI: 10.1038/ni.3049

Gauthier M, Ray A, Wenzel SE. Evolving concepts of asthma. Am J Respir Crit Care Med. 2015;192(6):660-668. DOI: 10.1164/rccm.201504-0763PP

Tan R, Liew MF, Lim HF, Leung BP, Fred-Wong WS. Promises and challenges of biologics for severe asthma. Biochem Pharmacol. 2020;179:114012. DOI: 10.1016/j.bcp.2020.114012

Fitzpatrick AM, Moore WC. Severe asthma phenotypes - how should they guide evaluation and treatment? J Allergy Clin Immunol Pract. 2017;5(4):901-908. DOI: 10.1016/j.jaip.2017.05.015

Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019;56(2):219-233. DOI: 10.1007/s12016-018-8712-1

Holguin F, Cardet JC, Chung KF, et al. Management of severe asthma: a European Respiratory Society/American Thoracic Society guideline. Eur Respir J. 2020;55(1):1900588. DOI: 10.1183/13993003.00588-2019

Bousquet J, Brusselle G, Buhl R, Busse WW, Cruz AA, Domingo C, et al. Care pathways for the selection of a biologic in severe asthma. Eur Respir J. 2017;50(6):1701782. DOI: 10.1183/13993003.01782-2017

Matucci A, Vultaggio A, Maggi E, Kasujee I. Is IgE or eosinophils the key player in allergic asthma pathogenesis? Are we asking the right question? Respir Res. 2018;19(1):113. DOI: 10.1186/s12931-018-0813-0

Oishi K, Matsunaga K. Three-step algorithm for biological therapy targeted IgE and IL-5 in severe asthma. Immun Inflamm Dis. 2018;6(3):374-376. DOI: 10.1002/iid3.233

Tran TN, Zeiger RS, Peters SP, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116(1):37-42. DOI: 10.1016/j.anai.2015.10.027

Domingo C. Overlapping effects of new monoclonal antibodies for severe asthma. Drugs. 2017;77(16):1769-1787. DOI: 10.1007/s40265-017-0810-5

Yanagibashi T, Satoh M, Nagai Y, Koike M, Takatsu K. Allergic diseases: from bench to clinic - contribution of the discovery of interleukin-5. Cytokine. 2017;98:59-70. DOI: 10.1016/j.cyto.2016.11.011

Thomson NC, Chaudhuri R. Omalizumab: clinical use for the management of asthma. Clin Med Insights Circ Respir Pulm Med. 2012;6:27-40. DOI: 10.4137/CCRPM.S7793

Boushey HA. Experiences with monoclonal antibody therapy for allergic asthma. J Allergy Clin Immunol. 2001;108(2 Suppl):S77-S83. DOI: 10.1067/mai.2001.116434

Plosker GL, Keam SJ. Omalizumab: a review of its use in the treatment of allergic asthma. BioDrugs. 2008;22(3):189-204. DOI: 10.2165/00063030-200822030-00005

Rodrigo GJ, Neffen H, Castro-Rodriguez JA. Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review. Chest. 2011;139(1):28-35. DOI: 10.1378/chest.10-1194

Humbert M, Beasley R, Ayres J, Slavin R, Hébert J, Ramos S, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 2005;60(3):309-316. DOI: 10.1111/j.1398-9995.2004.00772.x

Solèr M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;1(2):254-261. DOI: 10.1183/09031936.01.00092101. Errata en: Eur Respir J. 2001;18(4):739-740.

Niven R, Chung KF, Panahloo Z, Blogg M, Ayre G. Effectiveness of omalizumab in patients with inadequately controlled severe persistent allergic asthma: an open-label study. Respir Med. 2008;102(10):1371-1378. DOI: 10.1016/j.rmed.2008.06.002

Bousquet J, Siergiejko Z, Swiebocka E, Humbert M, Rabe KF, Smith N, et al. Persistency of response to omalizumab therapy in severe allergic (IgE-mediated) asthma. Allergy. 2011;66(5):671-678. DOI: 10.1111/j.1398-9995.2010.02522.x

Kulus M, Hébert J, Garcia E, Fowler-Taylor A, Fernández-Vidaurre C, Blogg M. Omalizumab in children with inadequately controlled severe allergic (IgE-mediated) asthma. Curr Med Res Opin. 2010;26(6):1285-1293. DOI: 10.1185/03007991003771338

Humbert M, Berger W, Rapatz G, Turk F. Add-on omalizumab improves day-to-day symptoms in inadequately controlled severe persistent allergic asthma. Allergy. 2008;63(5):592-596. DOI: 10.1111/j.1398-9995.2008.01654.x

Bousquet J, Rabe K, Humbert M, Chung KF, Berger W, Fox H, et al. Predicting and evaluating response to omalizumab in patients with severe allergic asthma. Respir Med. 2007;101(7):1483-1492. DOI: 10.1016/j.rmed.2007.01.011

Humbert M, Taillé C, Mala L, Le Gros V, Just J, Molimard M, et al. Omalizumab effectiveness in patients with severe allergic asthma according to blood eosinophil count: the STELLAIR study. Eur Respir J. 2018;51(5):1702523. DOI: 10.1183/13993003.02523-2017

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. 20113;154(9):573-582. DOI: 10.7326/0003-4819-154-9-201105030-00002. Errata en: Ann Intern Med. 2019;171(7):528.

Kavati A, Zhdanava M, Ortiz B, Lecocq J, Schiffman B, Pilon D, et al. Retrospective study on the association of biomarkers with real-world outcomes of omalizumab-treated patients with allergic asthma. Clin Ther. 2019;41(10):1956-1971. DOI: 10.1016/j.clinthera.2019.07.021

Siergiejko Z, Świebocka E, Smith N, Peckitt C, Leo H, Peachey G, et al. Oral corticosteroid sparing with omalizumab in severe allergic (IgE-mediated) asthma patients. Curr Med Res Opin. 2011;27(11):2223-2228. DOI: 10.1185/03007995.2011.620950

Molimard M, Buhl R, Niven R, Le Gros V, Thielen A, Thirlwell J, et al. Omalizumab reduces oral corticosteroid use in patients with severe allergic asthma: real-life data. Respir Med. 2010;104(9):1381-1385. DOI: 10.1016/j.rmed.2010.06.001

Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364(11):1005-1015. DOI: 10.1056/NEJMoa1009705

Teach SJ, Gill MA, Togias A, et al. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol. 2015;136(6):1476-1485. DOI: 10.1016/j.jaci.2015.09.008

Vignola AM, Humbert M, Bousquet J, Boulet LP, Hedgecock S, Blogg M, et al. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR. Allergy. 2004;59(7):709-717. DOI: 10.1111/j.1398-9995.2004.00550.x

Holgate ST, Chuchalin AG, Hébert J, Lötvall, Persson GB, et al. Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy. 2004;34(4):632-638. DOI: 10.1111/j.1365-2222.2004.1916.x

Milgrom H, Berger W, Nayak A, Gupta N, Pollard S, McAlary M, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001;108(2):E36. DOI: 10.1542/peds.108.2.e36

Hanania NA, Wenzel S, Rosén K, Hsieh HJ, Mosesova S, Choy DF, et al. Exploring the effects of omalizumab in allergic asthma: an analysis of biomarkers in the EXTRA study. Am J Respir Crit Care Med. 2013;187(8):804-811. DOI: 10.1164/rccm.201208-1414OC

Annez 1. Summary of product characteristics [En línea]. Países Bajos: European Medicines Agency; 2020.

Casale TB, Luskin AT, Busse W, Zeiger RS, Trzaskoma B, Yang M, et al. Omalizumab effectiveness by biomarker status in patients with asthma: evidence from PROSPERO, a prospective real-world study. J Allergy Clin Immunol Pract. 2019;7(1):156-164.e1. DOI: 10.1016/j.jaip.2018.04.043

Canonica GW, Rottoli P, Bucca C, Zappa MC, Michetti G, Macciocchi B, et al. Improvement of patient-reported outcomes in severe allergic asthma by omalizumab treatment: the real life observational PROXIMA study. World Allergy Organ J. 2018;11(1):33. DOI: 10.1186/s40413-018-0214-3

Bhutani M, Yang WH, Hébert J, de Takacsy F, Stril JL. The real world effect of omalizumab add on therapy for patients with moderate to severe allergic asthma: the ASTERIX Observational study. PLoS One. 2017;12(8):e0183869. DOI: 10.1371/journal.pone.0183869

Barnes N, Menzies-Gow A, Mansur AH, Specner D, Percival F, Radwan A, et al. Effectiveness of omalizumab in severe allergic asthma: a retrospective UK real-world study. J Asthma. 2013;50(5):529-536. DOI: 10.3109/02770903.2013.790419

Braunstahl GJ, Chen CW, 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):1141-1151. DOI: 10.1016/j.rmed.2013.04.017

Zazzali JL, Raimundo KP, Trzaskoma B, Rosén KE, Schatz M. Changes in asthma control, work productivity, and impairment with omalizumab: 5-year EXCELS study results. Allergy Asthma Proc. 2015;36(4):283-292. DOI: 10.2500/aap.2015.36.3849

MacDonald KM, Kavati A, Ortiz B, Alhossan A, Lee CS, Abraham I. Short- and long-term real-world effectiveness of omalizumab in severe allergic asthma: systematic review of 42 studies published 2008-2018. Expert Rev Clin Immunol. 2019;15(5):553-569. DOI: 10.1080/1744666X.2019.1574571

Deschildre A, Marguet C, Langlois C, Pin I, Rittié JL, Derelle J, et al. Real-life long-term omalizumab therapy in children with severe allergic asthma. Eur Respir J. 2015;46(3):856-859. DOI: 10.1183/09031936.00008115

Licari A, Castagnoli R, Denicolò C, Rossini L, Seminara M, Sacchi L, et al. Omalizumab in children with severe allergic asthma: the Italian real-life experience. Curr Respir Med Rev. 2017;13(1):36-42. DOI: 10.2174/1573398X13666170426094536

Sztafińska A, Jerzyńska J, Stelmach W, Woicka-Kolejwa K, Stelmach I. Quality of life in asthmatic children and their caregivers after two-year treatment with omalizumab, a real-life study. Postepy Dermatol Alergol. 2017;34(5):439-447. DOI: 10.5114/ada.2017.71109

Busse WW, Humbert M, Haselkorn T, Ortiz B, Trzsaskoma BL, Stephenson P, et al. Effect of omalizumab on lung function and eosinophil levels in adolescents with moderate-to-severe allergic asthma. Ann Allergy Asthma Immunol. 2020;124(2):190-196. DOI: 10.1016/j.anai.2019.11.016

Sabogal-Piñeros YS, Bal SM, Dijkhuis A, Majoor CF, Dierdorp BS, Dekker T, et al. Eosinophils capture viruses, a capacity that is defective in asthma. Allergy. 2019;74(10):1898-1909. DOI: 10.1111/all.13802

Hilvering B, Pavord ID. What goes up must come down: biomarkers and novel biologicals in severe asthma. Clin Exp Allergy. 2015;45(7):1162-1169. DOI: 10.1111/cea.12500

Prussin C, Griffith DT, Boesel KM, Lin H, Foster B, Casale TB. Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol. 2003;112(6):1147-1154. DOI: 10.1016/j.jaci.2003.10.003

López-Abente J, Benito-Villalvilla C, Jaumont X, Pfister P, Tassinari P, Palomares O. Late breaking abstract - IgE-FceR1 cross-linking impairs the capacity of plasmacytoid dendritic cells to induce in vitro functional regulatory T cells which can be restored by omalizumab. Eur Respir J. 2019;54:OA3803. DOI: 10.1183/13993003.congress-2019.OA3803

Roth M, Zhao F, Zhong J, Lardinois D, Tamm M. Serum IgE induced airway smooth muscle cell remodeling is independent of allergens and is prevented by omalizumab. PLoS One. 2015;10(9):e0136549. DOI: 10.1371/journal.pone.0136549

Hoshino M, Ohtawa J. Effects of adding omalizumab, an anti-immunoglobulin E antibody, on airway wall thickening in asthma. Respiration. 2012;83(6):520-528. DOI: 10.1159/000334701

Riccio AM, Dal-Negro RW, Micheletto C, de Ferrari L, Folli C, Chiappori A, et al. Omalizumab modulates bronchial reticular basement membrane thickness and eosinophil infiltration in severe persistent allergic asthma patients. Int J Immunopathol Pharmacol. 2012;25(2):475-484. DOI: 10.1177/039463201202500217

Humbert M, Bousquet J, Bachert C, Palomares O, Pfister P, Kottakis I, et al. IgE-mediated multimorbidities in allergic asthma and the potential for omalizumab therapy. J Allergy Clin Immunol Pract. 2019;7(5):1418-1429. DOI: 10.1016/j.jaip.2019.02.030

Brito Rde C, da Silva GA, Motta ME, Brito MC. The association of rhinoconjunctivitis and asthma symptoms in adolescents. Rev Port Pneumol. 2009;15(4):613-628. DOI: 10.1016/S0873-2159(15)30160-4

Hong S, Son DK, Lim WR, Kim SH, Kim H, Kwon H, et al. The prevalence of atopic dermatitis, asthma, and allergic rhinitis and the comorbidity of allergic diseases in children. Environ Health Toxicol. 2012;27:e2012006. DOI: 10.5620/eht.2012.27.e2012006

Larsen K. The clinical relationship of nasal polyps to asthma. Allergy Asthma Proc. 1996;17(5):243-249. DOI: 10.2500/108854196778662255

Philpott CM, Erskine S, Hopkins C, Kumar N, Anari S, Kara N, Ray J, et al. Prevalence of asthma, aspirin sensitivity and allergy in chronic rhinosinusitis: data from the UK National Chronic Rhinosinusitis Epidemiology Study. Respir Res. 2018;19(1):129. DOI: 10.1186/s12931-018-0823-y

Hill DA, Grundmeier RW, Ram G, Spergel JM. The epidemiologic characteristics of healthcare provider-diagnosed eczema, asthma, allergic rhinitis, and food allergy in children: a retrospective cohort study. BMC Pediatr. 2016;16:133. DOI: 10.1186/s12887-016-0673-z

Gupta RS, Warren CM, Smith BM, Jiang J, Blumenstock JA, Davis MM, et al. Prevalence and severity of food allergies among US adults. JAMA Netw Open. 2019;2(1):e185630. DOI: 10.1001/jamanetworkopen.2018.5630

Heck S, Al-Shobash S, Rapp D, Omlor A, Bekhit A, Flaig M, et al. High probability of comorbidities in bronchial asthma in Germany. NPJ Prim Care Respir Med. 2017;27(1):28. DOI: 10.1038/s41533-017-0026-x

Tay TR, Radhakrishna N, Hore-Lacy F, Smith C, Hoy R, Hew M, et al. Comorbidities in difficult asthma are independent risk factors for frequent exacerbations, poor control and diminished quality of life. Respirology. 2016;21(8):1384-1390. DOI: 10.1111/resp.12838

Jantunen J, Haahtela T, Salimäki J, et al. Multimorbidity in asthma, allergic conditions and COPD increase disease severity, drug use and costs: the Finnish pharmacy survey. Int Arch Allergy Immunol. 2019;179(4):273-280. DOI: 10.1159/000498861

Boulet LP, Boulay MÈ. Asthma-related comorbidities. Expert Rev Respir Med. 2011;5(3):377-393. DOI: 10.1586/ers.11.34

Colodenco D, Palomares O, Celis C, Kaplan A, Domingo C. Moving toward consensus on diagnosis and management of severe asthma in adults. Curr Med Res Opin. 2018;34(3):387-399. DOI: 10.1080/03007995.2017.1380617

Ledford DK, Lockey RF. Asthma and comorbidities. Curr Opin Allergy Clin Immunol. 2013;13(1):78-86. DOI: 10.1097/ACI.0b013e32835c16b6

Adelroth E, Rak S, Haahtela T, Rosenhall L, Zetterstorm O, Byrne A, et al. Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2000;106(2):253-259. DOI: 10.1067/mai.2000.108310

Casale TB, Condemi J, LaForce C, Nayak A, Rowe M, Watrous M, et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA. 2001;286(23):2956-2967. DOI: 10.1001/jama.286.23.2956

Chervinsky P, Casale T, Townley R, Tripathy I, Hedgecock S, Shen H, et al. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol. 2003;91(2):160-167. DOI: 10.1016/S1081-1206(10)62171-0

Masieri S, Cavaliere C, Begvarfaj E, Rosati D, Minni A. Effects of omalizumab therapy on allergic rhinitis: a pilot study. Eur Rev Med Pharmacol Sci. 2016;20(24):5249-5255.

Kopp MV, Hamelmann E, Zielen S, Kamin W, Bergmann KC, Sieder C, et al. Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma. Clin Exp Allergy. 2009;39(2):271-279. DOI: 10.1111/j.1365-2222.2008.03121.x

Sanchez J, Ramirez R, Diez S, Sus S, Echenique A, Olivares M, et al. Omalizumab beyond asthma. Allergol Immunopathol (Madr). 2012;40(5):306-315. DOI: 10.1016/j.aller.2011.09.011

de Klerk TA, Sharma V, Arkwright PD, Biswas S. Severe vernal keratoconjunctivitis successfully treated with subcutaneous omalizumab. J AAPOS. 2013;17(3):305-306. DOI: 10.1016/j.jaapos.2012.12.153

Doan S, Amat F, Gabison E, Saf S, Cochereau I, Just J. Omalizumab in severe refractory vernal keratoconjunctivitis in children: case series and review of the literature. Ophthalmol Ther. 2017;6(1):195-206. DOI: 10.1007/s40123-016-0074-2

Gevaert P, Calus L, van Zele T, Blomme K, de Ruyck N, Bachert C, et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J Allergy Clin Immunol. 2013;131(1):110-116.e1. DOI: 10.1016/j.jaci.2012.07.047

Vennera MC, Picado C, Mullol J, Alobid I, Bernal-Sprekelsen M. Efficacy of omalizumab in the treatment of nasal polyps. Thorax. 2011;66(9):824-825. DOI: 10.1136/thx.2010.152835

Penn R, Mikula S. The role of anti-IgE immunoglobulin therapy in nasal polyposis: a pilot study. Am J Rhinol. 2007;21(4):428-432. DOI: 10.2500/ajr.2007.21.3060

Iyengar SR, Hoyte EG, Loza A, Bonaccorso S, Chiang D, Umetsu DT, et al. Immunologic effects of omalizumab in children with severe refractory atopic dermatitis: a randomized, placebo-controlled clinical trial. Int Arch Allergy Immunol. 2013;162(1):89-93. DOI: 10.1159/000350486

Sheinkopf LE, Rafi AW, Do LT, Katz RM, Klaustermeyer WB. Efficacy of omalizumab in the treatment of atopic dermatitis: a pilot study. Allergy Asthma Proc. 2008;29(5):530-537. DOI: 10.2500/aap.2008.29.3160

Li JX, Fan LC, Li MH, Cao WJ, Xu JF. Beneficial effects of omalizumab therapy in allergic bronchopulmonary aspergillosis: a synthesis review of published literature. Respir Med. 2017;122:33-42. DOI: 10.1016/j.rmed.2016.11.019

Andorf S, Purington N, Block WM, Long AJ, Tupa D, Brittain E, et al. Anti-IgE treatment with oral immunotherapy in multifood allergic participants: a double-blind, randomised, controlled trial. Lancet Gastroenterol Hepatol. 2018;3(2):85-94. DOI: 10.1016/S2468-1253(17)30392-8

Wood RA, Kim JS, Lindblad R, Nadeau K, Henning AK, Dawson P, et al. A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow’s milk allergy. J Allergy Clin Immunol. 2016;137(4):1103-1110.e11. DOI: 10.1016/j.jaci.2015.10.005

Schneider LC, Rachid R, LeBovidge J, Blood E, Mittal M, Umetsu DT. A pilot study of omalizumab to facilitate rapid oral desensitization in high-risk peanut-allergic patients. J Allergy Clin Immunol. 2013;132(6):1368-1374. DOI: 10.1016/j.jaci.2013.09.046

Namazy JA, Blais L, Andrews EB, Scheuerle AE, Cabana MD, Thorp JM, et al. Pregnancy outcomes in the omalizumab pregnancy registry and a disease-matched comparator cohort. J Allergy Clin Immunol. 2020;145(2):528-536.e1. DOI: 10.1016/j.jaci.2019.05.019

Corren J, Casale TB, Lanier B, Buhl R, Holgate S, Jimenez P. Safety and tolerability of omalizumab. Clin Exp Allergy. 2009;39(6):788-797. DOI: 10.1111/j.1365-2222.2009.03214.x

Busse W, Buhl R, Fernandez-Vidaurre C, Blogg M, Zhu J, Eisner MD, et al. Omalizumab and the risk of malignancy: results from a pooled analysis. J Allergy Clin Immunol. 2012;129(4):983-989.e6. DOI: 10.1016/j.jaci.2012.01.033

Long A, Rahmaoui A, Rothman KJ, Guinan E, Eisner M, Bradley MS, et al. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. J Allergy Clin Immunol. 2014;134(3):560-567.e4. DOI: 10.1016/j.jaci.2014.02.007

Stevens WW, Schleimer RP, Kern RC. Chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol Pract. 2016;4(4):565-572. DOI: 10.1016/j.jaip.2016.04.012

Chung JH, Lee YJ, Kang TW, Kim KR, Jang DP, Kim IY, et al. Altered quality of life and psychological health (SCL-90-R) in patients with chronic rhinosinusitis with nasal polyps. Ann Otol Rhinol Laryngol. 2015;124(8):663-670. DOI: 10.1177/0003489415576181

Fokkens W, Lund V, Mullol J; European position paper on rhinosinusitis and nasal polyps 2007. Rhinol Suppl. 2007;20:1-136.

Johansson L, Akerlund A, Holmberg K, Melén I, Bende M. Prevalence of nasal polyps in adults: the Skövde population-based study. Ann Otol Rhinol Laryngol. 2003;112(7):625-629. DOI: 10.1177/000348940311200709

Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. European position paper on rhinosinusitis and nasal polyps 2012. Rhinol Suppl. 2012;50(23):3-298.

We J, Lee WH, Tan KL, Wee JH, Rhee CS, Lee CH, et al. Prevalence of nasal polyps and its risk factors: Korean National Health and Nutrition Examination Survey 2009-2011. Am J Rhinol Allergy. 2015;29(1):e24-e28. DOI: 10.2500/ajra.2015.29.4131

The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. European Network for Understanding Mechanisms of Severe Asthma. Eur Respir J. 2003;22(3):470-477. DOI: 10.1183/09031936.03.00261903

Moore WC, Bleecker ER, Curran-Everett D, et al. Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute’s Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119(2):405-413. DOI: 10.1016/j.jaci.2006.11.639

Haselkorn T, Borish L, Miller DP, Weiss ST, Wong DA. High prevalence of skin test positivity in severe or difficult-to-treat asthma. J Asthma. 2006;43(10):745-752. DOI: 10.1080/02770900601031540

Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73(7):1393-1414. DOI: 10.1111/all.13397

Maurer M, Weller K, Bindslev-Jensen C, Giménez-Arnau A, Bousquet PJ, Canonica GW, et al. Unmet clinical needs in chronic spontaneous urticaria. A GA²LEN task force report. Allergy. 2011;66(3):317-330. DOI: 10.1111/j.1398-9995.2010.02496.x

Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy. 2008;63(Suppl 86):8-160. DOI: 10.1111/j.1398-9995.2007.01620.x

Passali D, Cingi C, Staffa P, Passali F, Muluk NB, Bellussi ML. The International Study of the Allergic Rhinitis Survey: outcomes from 4 geographical regions. Asia Pac Allergy. 2018;8(1):e7. DOI: 10.5415/apallergy.2018.8.e7

Patel N, Herbert L, Green TD. The emotional, social, and financial burden of food allergies on children and their families. Allergy Asthma Proc. 2017;38(2):88-91. DOI: 10.2500/aap.2017.38.4028

Chafen JJ, Newberry SJ, Riedl MA, Bravata DM, Maglione M, Suttorp MJ, et al. Diagnosing and managing common food allergies: a systematic review. JAMA. 2010;303(18):1848-1856. DOI: 10.1001/jama.2010.582

Loh W, Tang MLK. The epidemiology of food allergy in the global context. Int J Environ Res Public Health. 2018;15(9):2043. DOI: 10.3390/ijerph15092043

Balp MM, Vietri J, Tian H, Isherwood G. The impact of chronic urticaria from the patient’s perspective: a survey in five European countries. Patient. 2015;8(6):551-558. DOI: 10.1007/s40271-015-0145-9

Mendelson MH, Bernstein JA, Gabriel S, Balp MM, Tian H, Vietri J, et al. Patient-reported impact of chronic urticaria compared with psoriasis in the United States. J Dermatolog Treat. 2017;28(3):229-236. DOI: 10.1080/09546634.2016.1227421

Vietri J, Turner SJ, Tian H, Isherwood G, Balp MM, Gabriel S. Effect of chronic urticaria on US patients: analysis of the National Health and Wellness Survey. Ann Allergy Asthma Immunol. 2015;115(4):306-311. DOI: 10.1016/j.anai.2015.06.030

Johnston DT, Sher L, Fineman SM, Zawadski R, Rosén K, Siri DD, et al. Prevalence of comorbities with peanut allergy: results from a phase 3, randomized, double-blind, placebo-controlled trial (PALISADE). J Allergy Clin Immunol. 2019;143(2):AB270. DOI: 10.1016/j.jaci.2018.12.824

Zhang N, Gevaert P, van Zele T, et al. An update on the impact of Staphylococcus aureus enterotoxins in chronic sinusitis with nasal polyposis. Rhinology. 2005;43(3):162-168.

Bracken SJ, Abraham S, MacLeod AS. Autoimmune theories of chronic spontaneous urticaria. Front Immunol. 2019;10:627. DOI: 10.3389/fimmu.2019.00627

Vashisht P, Casale T. Omalizumab for treatment of allergic rhinitis. Expert Opin Biol Ther. 2013;13(6):933-945. DOI: 10.1517/14712598.2013.795943

Anvari S, Miller J, Yeh CY, Davis CM. IgE-mediated food allergy. Clin Rev Allergy Immunol. 2019;57(2):244-260. DOI: 10.1007/s12016-018-8710-3

Prescribing information [En línea]. EE. UU.: Food and Drug Administration; 2020. Disponible en: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/103976s5224lbl.pdf

Burte E, Bousquet J, Siroux V, et al. The sensitization pattern differs according to rhinitis and asthma multimorbidity in adults: the EGEA study. Clin Exp Allergy. 2017;47(4):520-529. DOI: 10.1111/cea.12897

Kaplan AP, Giménez-Arnau AM, Saini SS. Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. Allergy. 2017;72(4):519-533. DOI: 10.1111/all.13083

A clinical trial of omalizumab in participants with chronic rhinosinusitis with nasal polyps (POLYP 1) [En línea]. EE. UU.: National Institutes of Health; 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT03280550

A clinical trial of omalizumab in participants with chronic rhinosinusituswith nasal polyps (POLYP 2) [En línea]. EE. UU.: National Institutes of Health; 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT03280537 [accessed January 2020]

Xolair® (omalizumab) significantly reduced nasal polyps and congestion symptoms in adults with chronic rhinosinusitis with nasal polyps in two phase III studies [En línea]. EE. UU.: Novartis; 2019.

Zhao ZT, Ji CM, Yu WJ, Meng L, Hawro T, Wei JF, et al. Omalizumab for the treatment of chronic spontaneous urticaria: A meta-analysis of randomized clinical trials. J Allergy Clin Immunol. 2016;137(6):1742-1750.e4. DOI: 10.1016/j.jaci.2015.12.1342

Tharp MD, Bernstein JA, Kavati A, Ortiz B, MacDonald K, Abraham I, et al. Benefits and harms of omalizumab treatment in adolescent and adult patients with chronic idiopathic (spontaneous) urticaria: a meta-analysis of “real-world” evidence. JAMA Dermatol. 2019;155(1):29-38. DOI: 10.1001/jamadermatol.2018.3447

Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG, et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2006;117(1):134-140. DOI: 10.1016/j.jaci.2005.09.036

Kuehr J, Brauburger J, Zielen S, Schauer U, Kamin W, Leupold W, et al. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol. 2002;109(2):274-280. DOI: 10.1067/mai.2002.121949

Okubo K, Ogino S, Nagakura T, Ishikawa T. Omalizumab is effective and safe in the treatment of Japanese cedar pollen-induced seasonal allergic rhinitis. Allergol Int. 2006;55(4):379-386. DOI: 10.2332/allergolint.55.379

Ogino S, Nagakura T, Okubo K, Sato N, Takahashi M, Ishikawa T. Re-treatment with omalizumab at one year interval for Japanese cedar pollen-induced seasonal allergic rhinitis is effective and well tolerated. Int Arch Allergy Immunol. 2009;149(3):239-245. DOI: 10.1159/000199719

Nagakura T, Ogino S, Okubo K, Sato N, Takahashi M, Ishikawa T. Omalizumab is more effective than suplatast tosilate in the treatment of Japanese cedar pollen-induced seasonal allergic rhinitis. Clin Exp Allergy. 2008;38(2):329-337. DOI: 10.1111/j.1365-2222.2007.02894.x

Yu C, Wang K, Cui X, et al. Clinical efficacy and safety of omalizumab in the treatment of allergic rhinitis: a systematic review and meta-analysis of randomized clinical trials. Am J Rhinol Allergy. 2020;34(2):196-208. DOI: 10.1177/1945892419884774

Study of efficacy and safety of omalizumab in severe Japanese cedar pollinosis adult and adolescent patients [En línea]. EE. UU.: National Institutes of Health; 2020. Disponible en: https://clinicaltrials.gov/ct2/show/NCT03369704

Takahashi M, Soejima K, Taniuchi S, Hatano Y, Yamanouchi S, Ishikawa H, et al. Oral immunotherapy combined with omalizumab for high-risk cow’s milk allergy: a randomized controlled trial. Sci Rep. 2017;7(1):17453. DOI: 10.1038/s41598-017-16730-6. Errata en: Sci Rep. 2018;21(1):12812.

MacGinnitie AJ, Rachid R, Gragg H, et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. J Allergy Clin Immunol. 2017;139(3):873-881.e8. DOI: 10.1016/j.jaci.2016.08.010

Sampson HA, Leung DY, Burks AW, Lack G, Bahna SL, Jones SM, et al. A phase II, randomized, doubleblind, parallelgroup, placebocontrolled oral food challenge trial of Xolair (omalizumab) in peanut allergy. J Allergy Clin Immunol. 2011;127(5):1309-1310.e1. DOI: 10.1016/j.jaci.2011.01.051

Vickery BP. Can omalizumab monotherapy benefit real-world food allergy patients? Lessons from an observational study. J Allergy Clin Immunol Pract. 2019;7(6):1910-1911. DOI: 10.1016/j.jaip.2019.05.007

Información para prescribir Xolair® (omalizumab) [En línea]. EE. UU.: Genentech USA, Inc./Novartis Pharmaceuticals Corporation. Disponible en: https://www.xolairhcp.com

Lieberman PL, Umetsu DT, Carrigan GJ, Rahmaoui A. Anaphylactic reactions associated with omalizumab administration: analysis of a case-control study. J Allergy Clin Immunol. 2016;138(3):913-915.e2. DOI: 10.1016/j.jaci.2016.03.030

Kim HL, Leigh R, Becker A. Omalizumab: practical considerations regarding the risk of anaphylaxis. Allergy Asthma Clin Immunol. 2010;6(1):32. DOI: 10.1186/1710-1492-6-32

Kallieri M, Papaioannou AI, Papathanasiou E, Ntontsi P, Papiris S, Loukides S. Predictors of response to therapy with omalizumab in patients with severe allergic asthma - a real life study. Postgrad Med. 2017;129(6):598-604. DOI: 10.1080/00325481.2017.1321945)

Probst M, Gogolka A, Krüll M, Noga O. In search of clinically relevant parameters to monitor successful omalizumab therapy in allergic asthma. Allergol Select. 2019;2(1):49-55. DOI: 10.5414/ALX01377E

Solidoro P, Patrucco F, de Blasio F, Brussino L, Dassetto D, Pivetta E, et al. Predictors of reversible airway obstruction with omalizumab in severe asthma: a real-life study. Ther Adv Respir Dis. 2019;13:1753466619841274. DOI: 10.1177/1753466619841274

Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108(2):184-190. DOI: 10.1067/mai.2001.117880

Buhl R, Hanf G, Solèr M, Bensch G, Wolfe J, Everhard F, et al. The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma. Eur Respir J. 2002;20(5):1088-1094. DOI: 10.1183/09031936.02.00016502

Corren J, Casale T, Deniz Y, Ashby M. Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol. 2003;111:87-90.

Ayres JG, Higgins B, Chilvers ER, Ayre G, Blogg M, Fox H. Efficacy and tolerability of anti- immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergic asthma. Allergy. 2004 Jul;59(7):701-708.

Bousquet J, Cabrera P, Berkman N, Buhl R, Holgate S, Wenzel S, et al. The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy. 2005;60(3):302-308. DOI: 10.1111/j.1398-9995.2004.00770.x

Chipps B, Buhl R, Beeh KM, Fox H, Thomas K, Reisner C. Improvement in quality of life with omalizumab in patients with severe allergic asthma. Curr Med Res Opin. 2006;22(11):2201-2208. DOI: 10.1185/030079906X148643

Niebauer K, Dewilde S, Fox-Rushby J, Revicki DA. Impact of omalizumab on quality-of-life outcomes in patients with moderate-to-severe allergic asthma. Ann Allergy Asthma Immunol. 2006;96(2):316-326. DOI: 10.1016/S1081-1206(10)61242-2

Niven R, McBryan D. A UK survey of oral corticosteroid use in patients treated with omalizumab. Thorax. 2007;62(3):A98. Abstract P91

Wu F, Takaro TK. Childhood asthma and environmental interventions. Environ Health Perspect. 2007;115(6):971-975. DOI: 10.1289/ehp.8989

Lanier BQ, Nayak A. Prevalence and impact of nighttime symptoms in adults and children with asthma: a survey. Postgrad Med. 2008;120(4):58-66. DOI: 10.3810/pgm.2008.11.1939

Brusselle G, Michils A, Louis R, Dupont L, Van de Maele B, Delobbe A, et al. “Real-life” effectiveness of omalizumab in patients with severe persistent allergic asthma: The PERSIST study. Respir Med. 2009;103(11):1633-1642. DOI: 10.1016/j.rmed.2009.06.014

Miller CW, Krishnaswamy N, Johnston C, Krishnaswamy G. Severe asthma and the omalizumab option. Clin Mol Allergy. 2008;6:4. DOI: 10.1186/1476-7961-6-4

Cazzola M, Camiciottoli G, Bonavia M, Gulotta C, Ravazzi A, Alessandrini A, et al. Italian real-life experience of omalizumab. Respir Med. 2010;104(10):1410-1416. DOI: 10.1016/j.rmed.2010.04.013

Korn S, Schumann C, Kropf C, Stoiber K, Thielen A, Taube C, et al. Effectiveness of omalizumab in patients 50 years and older with severe persistent allergic asthma. Ann Allergy Asthma Immunol. 2010;105(4):313-319. DOI: 10.1016/j.anai.2010.07.007

Bousquet J, Siergiejko Z, Swiebocka E, Humbert M, Rabe KF, Smith N, Leo J, Peckitt C, Maykut R, Peachey G. Persistency of response to omalizumab therapy in severe allergic (IgE-mediated) asthma. Allergy. 2011;66(5):671-678. DOI: 10.1111/j.1398-9995.2010.02522.x

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(9):573-582. DOI: 10.7326/0003-4819-154-9-201105030-00002. Erratum in: Ann Intern Med. 2019;171(7):528.

Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med. 2011;364(11):1005-1015. DOI: 10.1056/NEJMoa1009705

Schumann C, Kropf C, Wibmer T, Rüdiger S, Stoiber KM, Thielen A, et al. Omalizumab in patients with severe asthma: the XCLUSIVE study. Clin Respir J. 2012;6(4):215-227. DOI: 10.1111/j.1752-699X.2011.00263.x

Wilson SR, Rand CS, Cabana MD, Foggs MB, Halterman JS, Olson L, et al. Asthma outcomes: quality of life. J Allergy Clin Immunol. 2012;129(3 Suppl):S88-S123. DOI: 10.1016/j.jaci.2011.12.988

Lafeuille MH, Gravel J, Zhang J, Gorsh B, Figliomeni M, Lefebvre P. Association between consistent omalizumab treatment and asthma control. J Allergy Clin Immunol Pract. 2013;1(1):51-57. DOI: 10.1016/j.jaip.2012.08.006

Deschildre A, Marguet C, Salleron J, Pin I, Rittié JL, Derelle J, et al. Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey. Eur Respir J. 2013;42(5):1224-1233. DOI: 10.1183/09031936.00149812

Namazy J, Cabana MD, Scheuerle AE, Thorp JM Jr, Chen H, Carrigan G, et al. The Xolair Pregnancy Registry (EXPECT): the safety of omalizumab use during pregnancy. J Allergy Clin Immunol. 2015 Feb;135(2):407-412. DOI: 10.1016/j.jaci.2014.08.025

Teach SJ, Gill MA, Togias A, Sorkness CA, Arbes SJ Jr, Calatroni A, et al. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol. 2015;136(6):1476-1485. DOI: 10.1016/j.jaci.2015.09.008. Epub 2015 Oct 27. PMID: 26518090; PMCID: PMC4679705.

Ledford D, Busse W, Trzaskoma B, Omachi TA, Rosén K, Chipps BE, et al. A randomized multicenter study Evaluating Xolair Persistence Of Response after long-Term therapy. J Allergy Clin Immunol. 2017;140(1):162-169.e2. DOI: 10.1016/j.jaci.2016.08.054

Archivos adicionales

Publicado

2020-12-13 — Actualizado el 2020-12-18

Versiones