Immunobiological therapy in the treatment of severe asthma
DOI:
https://doi.org/10.33448/rsd-v13i5.45933Keywords:
Asthma; Anti-asthmatic agents; Biological treatment.Abstract
Introdução: A asma é uma doença inflamatória, crônica e heterogênea que acomete principalmente as vias aéreas inferiores, as quais apresentam sintomas respiratórios inespecíficos. Em sua maioria dos casos a asma possui bom manejo terapêutico, porém é crescente o número de diagnósticos de asma grave, os quais requerem o uso de imunobiológicos. O presente estudo objetiva uma análise detalhada sob o ponto de vista terapêutico e farmacológico dos principais imunobiológicos. Metodologia: A revisão narrativa da literatura foi realizada a partir da base de dados PUBMED utilizando as palavras chaves de “Severe Asthma”, “Treatment” e “Biological Therapy”, com o filtro de tempo nos últimos 10 anos que acarretaram em 56 artigos, os demais foram descartados por não possuir título ou resumo relacionado diretamente às palavras chaves ou possuírem restrições de acesso online. Resultados e Discussão: Em decorrência do maior conhecimento acerca da fisiopatologia da Asma, visto que apresenta diferentes vias de ativação inflamatória, destacadamente, as vias de ativação dos linfócitos B IgE, a resposta Th2,da ação de IL-5 que recruta neutrófilos e demais células inflamatórias, dentre outras interleucinas. Nesse contexto, o uso de imunobiológicos, por exemplo, Omalizumabe, Mepolizumabe, Reslizumabe, Dupilumabe e Tezepelumabe, em casos refratários à terapia convencional se destacam como uma alternativa assertiva e fisiológica diante do contexto patológico desenvolvido na asma grave. Conclusão: A asma não controlada e a Asma Grave são condições de refratariedade ao tratamento convencional da asma, dentro do espectro de potenciais complicações que podem surgir caso não iniciada terapêuticas avançadas.
References
A Matucci, Micheletto, C., & Vultaggio, A. (2023). Severe Asthma and Biologics: Managing Complex Patients. Journal of Investigational Allergology and Clinical Immunology, 33(3), 168–178. https://doi.org/10.18176/jiaci.0856
A Prabakaran. (2020). Treating asthma in the age of biologics. JAAPA, 33(6), 48–50. https://doi.org/10.1097/01.jaa.0000657220.41861.2d
Agache, I., Beltran, J., Akdis, C., Akdis, M., Canelo‐Aybar, C., Canonica, G. W., Casale, T., Chivato, T., Corren, J., Del Giacco, S., Eiwegger, T., Firinu, D., Gern, J. E., Hamelmann, E., Hanania, N., Mäkelä, M., Martín, I. H., Nair, P., O’Mahony, L., & Papadopoulos, N. G. (2020). Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. Allergy, https://doi.org/10.1111/all.14221
Agondi, R. C. (2010). Biomarcadores podem orientar a escolha de imunobiológicos no tratamento da asma. Arquivos de Asma, Alergia E Imunologia, 4(4), 379–381. https://doi.org/10.5935/2526-5393.20200060
Assaf, S. M., & Hanania, N. A. (2019b). Biological treatments for severe asthma. Current Opinion in Allergy and Clinical Immunology, 19(4), 379–386. https://doi.org/ 10.1097/aci.0000000000000549
asthma care. Allergology International. https://doi.org/10.1016/j.alit.2019.01.004
Bagnasco, D., Ferrando, M., Varricchi, G., Puggioni, F., Passalacqua, G., & Canonica, G. W. (2017). Anti-Interleukin 5 (IL-5) and IL-5Ra Biological Drugs: Efficacy, Safety, and Future Perspectives in Severe Eosinophilic Asthma. Frontiers in Medicine, 4. https://doi.org/10.3389/fmed.2017.00135
Bakakos, A., Loukides, S., Usmani, O. S., & Bakakos, P. (2020). Biologics in severe asthma: the overlap endotype - opportunities and challenges. Expert Opinion on Biological Therapy, 20(12), 1427–1434. https://doi.org/ 10.1080/14712598.2020.1809651
Bakakos, A., Rovina, N., & Bakakos, P. (2021). Treatment Challenges in Severe Eosinophilic Asthma: Differential Response to Anti-IL-5 and Anti-IL-5R Therapy. International Journal of Molecular Sciences, 22(8), 3969. https://doi.org/10.3390/ijms22083969
Bakakos, A., Schleich, F., & Bakakos, P. (2022). Biological Therapy of Severe Asthma and Nasal Polyps. Journal of Personalized Medicine, 12(6), 976. https://doi.org/10.3390/jpm12060976
Bel, E. H., Wenzel, S. E., Thompson, P. J., Prazma, C. M., Keene, O. N., Yancey, S. W., Ortega, H. G., & Pavord, I. D. (2014). Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma. New England Journal of Medicine, 371(13), 1189–1197. https://doi.org/10.1056/nejmoa1403291
Brom, L., Mendonça, T. N., Oliveira, F. R., Sarti, W., Melo, J. M. L., & Arruda, L. K. de P. (2015). New biologicals for asthma: anti interleukin-5 therapy. Brazilian Journal of Allergy and Immunology (BJAI), 3(5). https://doi.org/10.5935/2318-5015.20150024
Buhl, R., Bel, E., Bourdin, A., Dávila, I., Douglass, J. A., FitzGerald, J. M., Jackson, D. J., Lugogo, N. L., Matucci, A., Pavord, I. D., Wechsler, M. E., & Kraft, M. (2022). Effective Management of Severe Asthma with Biologic Medications in Adult Patients: A Literature Review and International Expert Opinion. The Journal of Allergy and Clinical Immunology: In Practice, 10(2), 422–432. https://doi.org/10.1016/ j.jaip.2021.10.059
Busse, W. W. (2018). Biological treatments for severe asthma. Current Opinion in Allergy and Clinical Immunology, 18(6), 509–518. https://doi.org/10.1097/aci.0000000000000487
Busse, W. W. (2019). Biological treatments for severe asthma: A major advance in Caminati, M., Bagnasco, D., Rosenwasser, L. J., Vianello, A., & Senna, G. (2020). Biologics for the Treatments of Allergic Conditions. Immunology and Allergy Clinics of North America, 40(4), 549–564. https://doi.org/10.1016/j.iac.2020.07.003
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. (2018). Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. New England Journal of Medicine, 378(26), 2486–2496.
https://doi.org/10.1056/nejmoa1804092
Castillo, J. R., Peters, S. P., & Busse, W. W. (2017). Asthma Exacerbations: Pathogenesis, Prevention, and Treatment. The Journal of Allergy and Clinical Immunology: In Practice, 5(4), 918–927. https://doi.org/10.1016/j.jaip.2017.05.001
Charles, D., Shanley, J., Temple, S., Rattu, A., Khaleva, E., & Roberts, G. (2022). Real-world efficacy of treatment with benralizumab, dupilumab, mepolizumab and reslizumab for severe asthma: A systematic review and meta-analysis. Clinical & Experimental Allergy. https://doi.org/10.1111/cea.14112
Clinical characteristics and treatment outcomes of severe asthma patients with a history of multiple biologic drugs use. (2021). Asian Pacific Journal of Allergy and Immunology. https://doi.org/10.12932/ap-170221-1070
Coleman, C., Khaleva, E., Rattu, A., Frankemölle, B., Nielsen, H., Roberts, G., & Williams, C. (2022). Narrative Review to capture patients’ perceptions and opinions about non-response and response to biological therapy for severe asthma. European Respiratory Journal. https://doi.org/10.1183/13993003.00837-2022
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. New England Journal of Medicine, 377(10), 936–946. https://doi.org/10.1056/nejmoa1704064
D??Amato, G., Bucchioni, E., Oldani, V., & Canonica, W. (2006). Treating Moderate-to-Severe Allergic Asthma with a Recombinant Humanized Anti-IgE Monoclonal Antibody (Omalizumab). Treatments in Respiratory Medicine, 5(6), 393–398. https://doi.org/10.2165/00151829-200605060-00004
Delgado, J., Dávila, I., & Domínguez-Ortega, J. (2021). Clinical Recommendations for the Management of Biological Treatments in Severe Asthma Patients: A Consensus Statement. Journal of Investigational Allergology and Clinical Immunology, 31(1), 36–43. https://doi.org/10.18176/jiaci.0638
Desai, M., Oppenheimer, J., & Lang, D. M. (2019). Immunomodulators and Biologics. *Clinics in Chest Medicine, 40(1), 179–192. https://doi.org/10.1016/j.ccm.2018.10.011
Dorscheid, D. R., Lee, J. K., Ramesh, W., Greenwald, M. J., & Jaime Del Carpio. (2022). Guidance for Administering Biologics for Severe Asthma and Allergic Conditions. Canadian Respiratory Journal, 2022, 1–9. https://doi.org/10.1155/2022/9355606
Dragonieri, S., & Carpagnano, G. E. (2021). Biological therapy for severe asthma. Asthma Research and Practice, 7(1). https://doi.org/10.1186/s40733-021-00078-w
Eger, K. A., & Bel, E. H. (2019). The emergence of new biologics for severe asthma. Current Opinion in Pharmacology, 46, 108–115. https://doi.org/10.1016/ j.coph.2019.05.005
Emma, R., Morjaria, J. B., Fuochi, V., Polosa, R., & Caruso, M. (2018). Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience. Therapeutic Advances in Respiratory Disease, 12, 175346661880849. https://doi.org/10.1177/1753466618808490
Fainardi, V., Pisi, G., & Chetta, A. (2016). Mepolizumab in the treatment of severe eosinophilic asthma. Immunotherapy, 8(1), 27–34. https://doi.org/10.2217/imt.15.102
García-Ramírez, U. N., Navarrete-Rodríguez, E. M., Chávez-García, A. A., & Trejo-Uribe, V. (2022). Guía práctica de seguimiento y manejo del paciente con asma grave tratado con biológicos [Practical guide for the follow-up and management of patients with severe asthma treated with biologics]. Revista medica del Instituto Mexicano del Seguro Social, 60(2), 201–210.
Giovannini, M., Mori, F., Barni, S., de Martino, M., & Novembre, E. (2019). Omalizumab and mepolizumab in the landscape of biological therapy for severe asthma in children: how to choose? Italian Journal of Pediatrics, 45(1). https://doi.org/10.1186/s13052-019-0737-4
Godar, M., Blanchetot, C., de Haard, H., Lambrecht, B. N., & Brusselle, G. (2017). Personalized medicine with biologics for severe type 2 asthma: current status and future prospects. MAbs, 10(1), 34–45. https://doi.org/ 10.1080/19420862.2017.1392425
Hering, T. (2019). Biologika — ein wichtiger Therapiefortschritt. MMW - Fortschritte Der Medizin, 161(5), 59–60. https://doi.org/10.1007/s15006-019-0276-32
Hilvering, B., & Pavord, I. D. (2015). What goes up must come down: biomarkers and novel biologicals in severe asthma. Clinical & Experimental Allergy, 45(7), 1162–1169. https://doi.org/10.1111/cea.12500
Krings, J. G., McGregor, M. C., Bacharier, L. B., & Castro, M. (2019). Biologics for Severe Asthma: Treatment-Specific Effects Are Important in Choosing a Specific Agent. The Journal of Allergy and Clinical Immunology: In Practice, 7(5), 1379–1392. https://doi.org/10.1016/j.jaip.2019.03.008
Kroes, J. A., Zielhuis, S. W., van Roon, E. N., & ten Brinke, A. (2020). Prediction of response to biological treatment with monoclonal antibodies in severe asthma. Biochemical Pharmacology, 179, 113978. https://doi.org/10.1016/j.bcp.2020.113978
Laurent Guilleminault, & Didier, A. (2019). L’asthme sévère à l’ère des biothérapies. La Presse Médicale, 48(3), 310–321. https://doi.org/10.1016/j.lpm.2019.03.001
Lim, H. F., & Nair, P. (2015). Efficacy and safety of reslizumab in patients with moderate to severe eosinophilic asthma. Expert Review of Respiratory Medicine, 9(2), 135–142. https://doi.org/10.1586/17476348.2015.1000867
Matera, M. G., Rogliani, P., Calzetta, L., & Cazzola, M. (2017). Pharmacokinetic/pharmacodynamic profile of reslizumab in asthma. Expert Opinion on Drug Metabolism & Toxicology, 14(2), 239–245. https://doi.org/10.1080/17425255.2018.1421170
McGregor, M. C., Krings, J. G., Nair, P., & Castro, M. (2019). Role of Biologics in Asthma. American Journal of Respiratory and Critical Care Medicine, 199(4), 433–445. https://doi.org/10.1164/rccm.201810-1944ci
Menzella, F., Ballarin, A., Maria Cristina Sartor, Ariel Fabian Floriani, Corsi, L., Dartora, C., Tonin, S., & Romagnoli, M. (2022). Comparison between clinical trials and real-world evidence studies on biologics for severe asthma. Journal of International Medical Research, 50(11), 030006052211336-030006052211336. https://doi.org/10.1177/03000605221133689
Menzella, F., Latorre, M., Ruggiero, P., Bagnasco, D., & Heffler, E. (2019). Reduction of oral corticosteroids in patients with severe eosinophilic asthma treated with Benralizumab: could it represent a marker of treatment efficacy? Expert Opinion on Biological Therapy, 19(7), 601–606. https://doi.org/10.1080/14712598.2019.1613367
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. New England Journal of Medicine, 384(19), 1800–1809. https://doi.org/10.1056/nejmoa2034975
Mirra, V., Montella, S., & Santamaria, F. (2018). Pediatric severe asthma: a case series report and perspectives on anti-IgE treatment. BMC Pediatrics, 18. https://doi.org/10.1186/s12887-018-1019-9
Miyokawa, R., Kivler, C., Louie, S., Godor, D., Tan, L., & Kenyon, N. (2020). Self-Administered Mepolizumab in the Management of Severe Asthma: Usability and Patient Acceptance. Patient Preference and Adherence, Volume 14, 1669–1682. https://doi.org/10.2147/ppa.s227465
Nagase, H., Suzukawa, M., Oishi, K., & Matsunaga, K. (2023). Biologics for severe asthma: The real-world evidence, effectiveness of switching, and prediction factors for the efficacy. Allergology International, 72(1), 11–23. https://doi.org/10.1016/j.alit.2022.11.008
Nair, P., Pizzichini, M. M. M., Kjarsgaard, M., Inman, M. D., Efthimiadis, A., Pizzichini, E., Hargreave, F. E., & O’Byrne, P. M. (2009). Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. New England Journal of Medicine, 360(10), 985–993. https://doi.org/10.1056/nejmoa0805435
New perspectives of biological therapy for severe asthma in adults and adolescents. (2022). Swiss Medical Weekly, 152(21-22). https://doi.org/10.4414/smw.2022.w30176
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. Journal of Allergy and Clinical Immunology, 151(3), 747–755. https://doi.org/10.1016/j.jaci.2022.11.021
Ntontsi, P., Samitas, K., Zervas, E., & Gaga, M. (2020). Severe asthma: what is new in the new millennium. Current Opinion in Allergy & Clinical Immunology, 20(2), 202–207. https://doi.org/10.1097/aci.0000000000000623
Paoletti, G., Pepys, J., Casini, M., Di Bona, D., Heffler, E., Goh, C. Y. Y., Price, D. B., & Canonica, G. W. (2022). Biologics in severe asthma: the role of real-world evidence from registries. European Respiratory Review: An Official Journal of the European Respiratory Society, 31(164), 210278. https://doi.org/10.1183/16000617.0278-2021
Papathanassiou, E., Loukides, S., & Bakakos, P. (2016). Severe asthma: anti-IgE or anti-IL-5? European Clinical Respiratory Journal, 3(1), 31813. https://doi.org/10.3402/ecrj.v3.31813
Papi, A., Brightling, C., Pedersen, S. E., & Reddel, H. K. (2018). Asthma. The Lancet, 391(10122), 783–800. https://doi.org/10.1016/s0140-6736(17)33311-1
Peer Ameen Shah, & Brightling, C. E. (2023). Biologics for severe asthma—Which, when and why? Respirology, 28(8), 709–721. https://doi.org/10.1111/resp.14520
Pelaia, C., Calabrese, C., Terracciano, R., de Blasio, F., Vatrella, A., & Pelaia, G. (2018). Omalizumab, the first available antibody for biological treatment of severe asthma: more than a decade of real-life effectiveness. Therapeutic Advances in Respiratory Disease, 12, 175346661881019. https://doi.org/10.1177/1753466618810192
Pelaia, C., Calabrese, C., Vatrella, A., Busceti, M. T., Garofalo, E., Lombardo, N., Terracciano, R., & Pelaia, G. (2018). Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma. BioMed Research International, 2018, 1–9. https://doi.org/10.1155/2018/4839230
Pelaia, C., Crimi, C., Vatrella, A., Tinello, C., Terracciano, R., & Pelaia, G. (2020). Molecular Targets for Biological Therapies of Severe Asthma. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.603312
Pelaia, C., Pelaia, G., Crimi, C., Maglio, A., Armentaro, G., Calabrese, C., Sciacqua, A., Gallelli, L., & Vatrella, A. (2022). Biological Therapy of Severe Asthma with Dupilumab, a Dual Receptor Antagonist of Interleukins 4 and 13. Vaccines, 10(6), 974. https://doi.org/10.3390/vaccines10060974
Pelaia, C., Vatrella, A., Bruni, A., Terracciano, R., & Pelaia, G. (2018). Benralizumab in the treatment of severe asthma: design, development and potential place in therapy. Drug Design, Development and Therapy, Volume 12(https://doi.org/10.2147/dddt.s155307), 619–628. https://doi.org/10.2147/dddt.s155307
Pelaia, G., Canonica, W., Matucci, A., Paolini, R., Triggiani, M., & Paggiaro, P. (2017). Targeted therapy in severe asthma today: focus on immunoglobulin E. Drug Design, Development and Therapy, Volume 11, 1979–1987. https://doi.org/10.2147/dddt.s130743
Porsbjerg, C. M., Sverrild, A., Lloyd, C. M., Menzies-Gow, A. N., & Bel, E. H. (2020). Anti-alarmins in asthma: targeting the airway epithelium with next-generation biologics. European Respiratory Journal, 56(5), 2000260. https://doi.org/ 10.1183/13993003.00260-2020
Quirce, S., Phillips-Angles, E., Domínguez-Ortega, J., & Barranco, P. (2017). Biologics in the treatment of severe asthma. Allergologia et Immunopathologia, 45, 45–49. https://doi.org/10.1016/j.aller.2017.09.012
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. (2018). Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. New England Journal of Medicine, 378(26), 2475–2485. https://doi.org/10.1056/nejmoa1804093
Ragnoli, B., Morjaria, J., Pignatti, P., Montuschi, P., Barbieri, M., Mondini, L., Ruggero, L., Trotta, L., & Malerba, M. (2022). Dupilumab and tezepelumab in severe refractory asthma: new opportunities. Therapeutic Advances in Chronic Disease, 13, 204062232210973. https://doi.org/10.1177/20406223221097327
Robinson, D. S., & Kariyawasam, H. H. (2015). Mepolizumab for eosinophilic severe asthma: recent studies. Expert Opinion on Biological Therapy, 15(6), 909–914. https://doi.org/10.1517/14712598.2015.1041911
Rogliani, P., Calzetta, L., Matera, M. G., Laitano, R., Ritondo, B. L., Hanania, N. A., & Cazzola, M. (2019). Severe Asthma and Biological Therapy: When, Which, and for Whom. Pulmonary Therapy, 6(1), 47–66. https://doi.org/10.1007/s41030-019-00109-1
Rother, E. T. (2007). Systematic literature review X narrative review. Acta Paulista de Enfermagem, 20(2), v–vi. https://doi.org/10.1590/s0103- 21002007000200001
Schoettler, N., & Strek, M. E. (2019). Recent Advances in Severe Asthma. Chest, 157(3). https://doi.org/10.1016/j.chest.2019.10.009
Sivan, P., Noam, N., Isaac, S., Murad, S., & Fox, B. (2022). Biologic treatments for severe asthma: 4 year experience of a single medical center. The Israel Medical Association journal : IMAJ, 25(12), 815–819.
Snyder, H. (2019). Literature Review as a Research methodology: an Overview and Guidelines. Journal of Business Research, 104(1), 333–339. https://doi.org/10.1016/j.jbusres.2019.07.039
Solé, D., Sano, F., Rosário, N. A., Antila, M. A., Aranda, C. S., Chong-Neto, H. J., Cocco, R. R., Condino-Neto, A., Costa, R. A., Ensina, L. F., Giavina-Bianchi, P., Goudouris, E. S., Mallozi, M. C., Morandi, J. L. B., Perazzio, S. F., Reali, A. C. R., Rios, J. L. M., Rosário, C. S., Segundo, G. R. S., & Serpa, F. S. (197 C.E.). Guia prático de atualização: medicamentos biológicos no tratamento da asma, doenças alérgicas e imunodeficiências. Arquivos de Asma, Alergia E Imunologia, 3(3), 207–258. https://doi.org/10.5935/2526-5393.20190035
Tan, R., Liew, M. F., Lim, H. F., Leung, B. P., & Wong, W. S. F. (2020). Promises and challenges of biologics for severe asthma. Biochemical Pharmacology, 179, 114012. https://doi.org/10.1016/j.bcp.2020.114012
Trivedi, A., Pavord, I. D., & Castro, M. (2016). Bronchial thermoplasty and biological therapy as targeted treatments for severe uncontrolled asthma. The Lancet Respiratory Medicine, 4(7), 585–592. https://doi.org/10.1016/s2213-2600(16)30018-2
Varricchi, G., Ferri, S., Pepys, J., Poto, R., Spadaro, G., Nappi, E., Paoletti, G., Virchow, J. C., Heffler, E., & Canonica, W. G. (2022). Biologics and airway remodeling in severe asthma. Allergy, 77(12). https://doi.org/10.1111/all.15473
Versão, H., & Pdf, E. (n.d.). Informações Médicas Asma Brônquica Tratamento da Asma BIOLÓGICOS NA ASMA -ANTI-IL-5, IL-5Rα, Anti-IL-4/IL-13. https://www.asmabronquica.com.br/PDF/biologicos.pdf
Venkatesan, P. (2023). 2023 GINA report for asthma. https://doi.org/10.1016/s2213-2600(23)00230-8
Wan, X. C., & Woodruff, P. G. (2016). Biomarkers in Severe Asthma. Immunology and Allergy Clinics of North America, 36(3), 547–557. https://doi.org/10.1016/ j.iac.2016.03.004
Wenzel, S., Castro, M., Corren, J., Maspero, J., Wang, L., Zhang, B., Pirozzi, G., Sutherland, E. R., Evans, R. R., Joish, V. N., Eckert, L., Graham, N. M. H., Stahl, N., Yancopoulos, G. D., Louis-Tisserand, M., & Teper, A. (2016). 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. The Lancet, 388(10039), 31–44. https://doi.org/10.1016/s0140-6736(16)30307-5
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 David Evangelista Barros de Oliveira; Carlos Gustavo Alves Leitão; Fernanda Oliveira Falcão; João Pedro de Paiva Torquato; José de Ribamar Barroso Jucá Neto; Marcela Alina Jereissati de Castro; Simone Castelo Branco Fortaleza
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
1) Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
2) Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
3) Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.
