常见过敏性疾病的生物靶向治疗及其导致的严重过敏反应研究进展

doi:10.19983/j.issn.2096-8493.20230018

摘要/Abstract

摘要：

随着对发病机制的了解,生物靶向药物作为一种精准医疗的手段被逐步应用于多种常见的过敏性疾病,并取得了良好的治疗效果。但是相较于其他国家,中国获批的药物种类更少,患者的治疗选择也更局限,扩展药物种类及适应证是发展方向。与任何新兴药物一样,安全性仍然是生物靶向药物的关键性问题,其中,严重过敏反应作为一种速发的、可危及生命的严重不良反应已经被发现发生于多种生物靶向药物的治疗过程中,但是人们对它的了解和重视程度并不够。作者回顾了8种在国际范围内用于治疗常见过敏反应的生物靶向药物:奥马珠单抗(抗IgE)、美泊利单抗(抗IL-5)、雷珠单抗(抗IL-5)、本拉珠单抗(抗IL-5)、度普利尤单抗(抗IL-4、IL-13)、曲罗芦单抗(抗IL-13)、奈莫利珠单抗(抗IL-31R)和替塞单抗(抗TSLP),并总结归纳了几种药物的严重过敏反应发生率,以期促进医护人员对此关注,在药物使用后进行合理必要的监管,并能够在严重过敏反应发生时及时识别并予以处理。

关键词: 过敏反应, 药物过敏, 生物靶向治疗

Abstract:

With the understanding of pathogenesis, biologics are gradually being applied as a mean of precision medicine for a variety of common allergic diseases, and good therapeutic results have been achieved. However, compared to foreign countries, China has fewer approved drugs and patients’ treatment options are more limited, so expanding the range of drugs and indications is the way forward. As with any emerging drug, safety remains a key issue for biologics, where anaphylaxis, a rapid-onset, life-threatening and serious adverse reaction, have been found to occur in the treatment of a variety of biologics, but it is not well understood or taken seriously enough. The authors therefore review eight biologics used internationally to treat common allergic reactions: omalizumab (anti-IgE), mepolizumab (anti-IL-5), reslizumab (anti-IL-5), benralizumab (anti-IL-5), dupilumab (anti-IL-4, IL-13), tralokinumab (anti-IL-13), nemolizumab (anti-IL-31R) and tesepelumab (anti-TSLP), and summarises the incidence of anaphylaxis to these biologics in order to promote awareness among healthcare professionals, to provide reasonable and necessary supervision after drug administration, and to be able to identify and manage anaphylaxis when they occur.

Key words: Anaphylaxis, Drug hypersensitivity, Biotargeted therapy

中图分类号:

R781.6+7

茹一, 李丽莎, 关凯. 常见过敏性疾病的生物靶向治疗及其导致的严重过敏反应研究进展[J]. 结核与肺部疾病杂志, 2023, 4(2): 169-177. doi: 10.19983/j.issn.2096-8493.20230018

Ru Yi, Li Lisha, Guan Kai. Research advance of biological target therapy and its cause of anaphylaxis for common allergic diseases[J]. Journal of Tuberculosis and Lung Disease, 2023, 4(2): 169-177. doi: 10.19983/j.issn.2096-8493.20230018

图/表 2

表1

8种生物靶向药物在不同国家/地区批准上市时间、适用患者年龄和药物适应证

生物靶向药物	美国				欧盟				日本				中国
生物靶向药物	上市年份	适用患者年龄 (岁)		适应证	上市年份	适用患者年龄 (岁)		适应证	上市年份	适用患者年龄 (岁)		适应证	上市年份	适用患者年龄 (岁)		适应证
奥马珠单抗	2003	≥6	中重度持续性过敏性哮喘		2005	≥6	重度持续性过敏性哮喘		2009	成人与儿童	过敏性哮喘		2018	≥6	中重度持续性过敏性哮喘
	2014	≥12	慢性自发性荨麻疹		2014	≥12	慢性自发性荨麻疹		2017	≥12	慢性自发性荨麻疹
	2020	≥18	鼻息肉		2020	≥18	重度慢性鼻窦炎伴鼻息肉(CRSwNP)		2019	≥12	季节性过敏性鼻炎
美泊利单抗	2015	≥6	重度嗜酸性粒细胞性哮喘		2015	≥6	重度嗜酸性粒细胞性哮喘		2016	≥6	支气管哮喘		2022	≥18	嗜酸性肉芽肿性多血管炎
	2021	≥18	重度慢性鼻窦炎伴鼻息肉(CRSwNP)		2021	≥18	重度慢性鼻窦炎伴鼻息肉(CRSwNP)
雷珠单抗	2016	≥18	重度嗜酸性粒细胞性哮喘		2016	≥18	重度嗜酸性粒细胞性哮喘		尚未批准用于过敏性疾病				尚未批准用于过敏性疾病
本拉珠单抗	2017	≥12	重度嗜酸性粒细胞性哮喘		2018	≥18	重度嗜酸性粒细胞性哮喘		2018	≥18	重度嗜酸性粒细胞性哮喘		尚未批准用于过敏性疾病
度普利尤单抗	2017	≥6	中重度特应性皮炎		2017	≥6	中重度特应性皮炎		2018	≥18	中重度特应性皮炎		2020	≥6	中重度特应性皮炎
	2019	≥6	中重度嗜酸性粒细胞性哮喘		2019	≥6	中重度嗜酸性粒细胞性哮喘		2019	≥12	中重度嗜酸性粒细胞性哮喘
	2019	≥18	重度慢性鼻窦炎伴鼻息肉(CRSwNP)		2019	≥18	重度慢性鼻窦炎伴鼻息肉(CRSwNP)		2020	≥18	重度慢性鼻窦炎伴鼻息肉(CRSwNP)
替塞单抗	2021	≥12	重度哮喘		2021	≥12	重度哮喘		2021	≥12	重度哮喘		尚未批准用于过敏性疾病
曲罗芦单抗	2012	≥18	中重度特应性皮炎		2021	≥12	中重度特应性皮炎		尚未批准用于过敏性疾病				尚未批准用于过敏性疾病
奈莫利珠单抗	尚未批准用于过敏性疾病				尚未批准用于过敏性疾病				2022	≥13	特应性皮炎伴瘙痒		尚未批准用于过敏性疾病

表1

表2

参考文献 71

[1]	Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of anaphylaxis: Summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol, 2006, 117(2): 391-397. doi:10.1016/j.jaci.2005.12.1303. doi: 10.1016/j.jaci.2005.12.1303 URL
[2]	Sutton BJ, Gould HJ. The human IgE network. Nature, 1993, 366(6454): 421-428. doi:10.1038/366421a0. doi: 10.1038/366421a0
[3]	Heusser C, Jardieu P. Therapeutic potential of anti-IgE antibodies. Curr Opin Immunol, 1997, 9(6): 805-813. doi:10.1016/S0952-7915(97)80182-3. doi: 10.1016/S0952-7915(97)80182-3 pmid: 9492982
[4]	Davies AM, Allan EG, Keeble AH, et al. Allosteric mechanism of action of the therapeutic anti-IgE antibody omalizumab. J Biol Chem, 2017, 292(24): 9975-9987. doi:10.1074/jbc.M117.776476. doi: 10.1074/jbc.M117.776476 pmid: 28438838
[5]	Presta LG, Lahr SJ, Shields RL, et al. Humanization of an antibody directed against IgE. J Immunol, 1993, 151(5): 2623-2632. pmid: 8360482
[6]	Redhu NS, Gounni AS. The high affinity IgE receptor (FcεRI) expression and function in airway smooth muscle. Pulm Pharmacol Ther, 2013, 26(1): 86-94. doi:10.1016/j.pupt.2012.04.004. doi: 10.1016/j.pupt.2012.04.004 pmid: 22580035
[7]	Humbert M, Busse W, Hanania NA, et al. Omalizumab in Asthma: An Update on Recent Developments. J Allergy Clin Immunol Pract, 2014, 2(5): 525-536.e1. doi:10.1016/j.jaip.2014.03.010. doi: 10.1016/j.jaip.2014.03.010 pmid: 25213045
[8]	Corren J, Shapiro G, Reimann J, et al. Allergen skin tests and free IgE levels during reduction and cessation of omalizumab therapy. J Allergy Clin Immunol, 2008, 121(2): 506-511. doi:10.1016/j.jaci.2007.11.026. doi: 10.1016/j.jaci.2007.11.026 pmid: 18269927
[9]	Cox L, Platts-Mills TA, Finegold I, et al. American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. J Allergy Clin Immunol, 2007, 120(6): 1373-1377. doi:10.1016/j.jaci.2007.09.032. doi: 10.1016/j.jaci.2007.09.032 URL
[10]	Genentech, Inc.Xolair (omalizumab) [product insert]. South San Francisco, 2007.
[11]	Tharp MD, Bernstein JA, Kavati A, 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. doi:10.1001/jamadermatol.2018.3447. doi: 10.1001/jamadermatol.2018.3447 URL
[12]	Gevaert P, Omachi TA, Corren J, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J Allergy Clin Immunol, 2020, 146(3): 595-605. doi:10.1016/j.jaci.2020.05.032. doi: S0091-6749(20)30752-1 pmid: 32524991
[13]	Li L, Wang Z, Cui L, et al. Anaphylactic risk related to omalizumab, benralizumab, reslizumab, mepolizumab, and dupilumab. Clin Transl Allergy, 2021, 11(4):e12038. doi:10.1002/clt2.12038. doi: 10.1002/clt2.12038
[14]	Corren J, Casale TB, Lanier B, et al. Safety and tolerability of omalizumab. Clin Exp Allergy, 2009, 39(6): 788-797. doi:10.1111/j.1365-2222.2009.03214.x. doi: 10.1111/j.1365-2222.2009.03214.x pmid: 19302249
[15]	Lieberman P, Rahmaoui A, Wong DA. The Safety and Interpretability of Skin Tests with Omalizumab. Ann Allergy Asthma Immunol, 2010, 105(6): 493-495. doi:10.1016/j.anai.2010.10.008. doi: 10.1016/j.anai.2010.10.008 URL
[16]	Owens G, Petrov A. Successful Desensitization of Three Patients with Hypersensitivity Reactions to Omalizumab. Curr Drug Saf, 2011, 6(5):339-342. doi:10.2174/157488611798918692. doi: 10.2174/157488611798918692 pmid: 22424542
[17]	Steele RH, Limaye S, Cleland B, et al. Hypersensitivity reactions to the polysorbate contained in recombinant erythropoietin and darbepoietin (Case Report). Nephrology, 2005, 10(3): 317-320. doi:10.1111/j.1440-1797.2005.00389.x. doi: 10.1111/j.1440-1797.2005.00389.x pmid: 15958049
[18]	Price KS, Hamilton RG. Anaphylactoid reactions in two patients after omalizumab administration after successful long-term therapy. Allergy Asthma Proc, 2007, 28(3): 313-319. doi:10.2500/aap.2007.28.3003. doi: 10.2500/aap.2007.28.3003 pmid: 17619560
[19]	Busse WW, Ring J, Huss-Marp J, et al. A review of treatment with mepolizumab, an anti-IL-5 mAb, in hypereosinophilic syndromes and asthma. J Allergy Clin Immunol, 2010, 125(4): 803-813. doi:10.1016/j.jaci.2009.11.048. doi: 10.1016/j.jaci.2009.11.048 pmid: 20371394
[20]	Tan LD, Bratt JM, Godor D, et al. Benralizumab: a unique IL-5 inhibitor for severe asthma. J Asthma Allergy, 2016, 9: 71-81. doi:10.2147/JAA.S78049. doi: 10.2147/JAA.S78049 pmid: 27110133
[21]	Bel EH, I Bernstein D, Bjermer L, et al. Usability of mepolizumab single-use prefilled syringe for patient self-administration. J Asthma, 2020, 57(7): 755-764. doi:10.1080/02770903.2019.1604745. doi: 10.1080/02770903.2019.1604745 pmid: 31017022
[22]	Harvey ES, Langton D, Katelaris C, et al. Mepolizumab effectiveness and identification of super-responders in severe asthma. Eur Respir J, 2020, 55(5): 1902420. doi:10.1183/13993003.02420-2019. doi: 10.1183/13993003.02420-2019 URL
[23]	Khatri S, Moore W, Gibson PG, et al. Assessment of the long-term safety of mepolizumab and durability of clinical response in patients with severe eosinophilic asthma. J Allergy Clin Immunol, 2019, 143(5): 1742-1751.e7. doi:10.1016/j.jaci.2018.09.033. doi: S0091-6749(18)31479-9 pmid: 30359681
[24]	Han JK, Bachert C, Fokkens W, et al.Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med, 2021, 9(10): 1141-1153. doi:10.1016/S2213-2600(21)00097-7. doi: 10.1016/S2213-2600(21)00097-7 pmid: 33872587
[25]	Jingo K, Harada N, Nishioki T, et al. Anaphylaxis to three humanized antibodies for severe asthma: a case study. Allergy Asthma Clin Immunol, 2020, 16(1): 46. doi:10.1186/s13223-020-00446-w. doi: 10.1186/s13223-020-00446-w
[26]	Lugogo N, Domingo C, Chanez P, et al. Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase Ⅲb Study. Clin Ther, 2016, 38(9): 2058-2070.e1. doi:10.1016/j.clinthera.2016.07.010. doi: 10.1016/j.clinthera.2016.07.010 pmid: 27553751
[27]	Hillas G, Fouka E, Papaioannou AI. Antibodies targeting the interleukin-5 signaling pathway used as add-on therapy for patients with severe eosinophilic asthma: a review of the mechanism of action, efficacy, and safety of the subcutaneously administered agents, mepolizumab and benralizumab. Expert Rev Respir Med, 2020, 14(4): 353-365. doi:10.1080/17476348.2020.1718495. doi: 10.1080/17476348.2020.1718495 URL
[28]	Castro M, Zangrilli J, Wechsler ME, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med, 2015, 3(5): 355-366. doi:10.1016/S2213-2600(15)00042-9. doi: 10.1016/S2213-2600(15)00042-9 pmid: 25736990
[29]	Bjermer L, Lemiere C, Maspero J, et al. Reslizumab for Inade-quately Controlled Asthma With Elevated Blood Eosinophil Levels. Chest, 2016, 150(4): 789-798. doi:10.1016/j.chest.2016.03.032. doi: S0012-3692(16)47551-3 pmid: 27056586
[30]	Castro M, Mathur S, Hargreave F, et al. Reslizumab for Poorly Controlled, Eosinophilic Asthma: A Randomized, Placebo-controlled Study. Am J Respir Crit Care Med, 2011, 184(10): 1125-1132. doi:10.1164/rccm.201103-0396OC. doi: 10.1164/rccm.201103-0396OC URL
[31]	Farne HA, Wilson A, Powell C, et al. Anti-IL5 therapies for asthma. Cochrane Database Syst Rev, 2017, 9(9):CD010834. doi:10.1002/14651858.CD010834.pub3. doi: 10.1002/14651858.CD010834.pub3
[32]	Virchow JC, Katial R, Brusselle GG, et al. Safety of Reslizumab in Uncontrolled Asthma with Eosinophilia: A Pooled Analysis from 6 Trials. J Allergy Clin Immunol Pract, 2020, 8(2): 540-548.e1. doi:10.1016/j.jaip.2019.07.038. doi: S2213-2198(19)30701-9 pmid: 31404668
[33]	Simpson E, Udkoff J, Borok J, et al. Atopic dermatitis: emerging therapies. Semin Cutan Med Surg, 2017, 36(3): 124-130. doi:10.12788/j.sder.2017.0137. doi: 10.12788/j.sder.2017.0137 pmid: 28895959
[34]	Cazzola M, Matera MG, Levi-Schaffer F, et al. Safety of humanized monoclonal antibodies against IL-5 in asthma: focus on reslizumab. Expert Opin Drug Saf, 2018, 17(4): 429-435. doi:10.1080/14740338.2018.1446940. doi: 10.1080/14740338.2018.1446940 pmid: 29486600
[35]	Pepper AN, Renz H, Casale TB, et al. Biologic Therapy and Novel Molecular Targets of Severe Asthma. J Allergy Clin Immunol Pract, 2017, 5(4): 909-916. doi:10.1016/j.jaip.2017.04.038. doi: S2213-2198(17)30354-9 pmid: 28689841
[36]	FitzGerald JM, Bleecker ER, Nair P, et al.Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial.Lancet, 2016, 388(10056): 2128-2141. doi:10.1016/S0140-6736(16)31322-8. doi: S0140-6736(16)31322-8 pmid: 27609406
[37]	Bleecker ER, FitzGerald JM, Chanez P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet, 2016, 388(10056): 2115-2127. doi:10.1016/S0140-6736(16)31324-1. doi: S0140-6736(16)31324-1 pmid: 27609408
[38]	Öztürk Aktaş Ö, Şekerel BE, Kalyoncu AF. Glucocorticoid Sparing of Benralizumab in Asthma. N Engl J Med, 2017, 377(12): 1204-1205. doi:10.1056/NEJMc1709523. doi: 10.1056/NEJMc1709523 URL
[39]	Nowak RM, Parker JM, Silverman RA, et al. A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma. Am J Emerg Med, 2015, 33(1): 14-20. doi:10.1016/j.ajem.2014.09.036. doi: 10.1016/j.ajem.2014.09.036 pmid: 25445859
[40]	Busse WW, Bleecker ER, FitzGerald JM, 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. doi: 10.1016/S2213-2600(18)30406-5 pmid: 30416083
[41]	Krings JG, McGregor MC, Bacharier LB, et al. Biologics for Severe Asthma: Treatment-Specific Effects Are Important in Choosing a Specific Agent. J Allergy Clin Immunol Pract, 2019, 7(5): 1379-1392. doi:10.1016/j.jaip.2019.03.008. doi: S2213-2198(19)30271-5 pmid: 31076056
[42]	Corren J, Busse W, Meltzer EO, et al. A Randomized, Controlled, Phase 2 Study of AMG 317, an IL-4Rα Antagonist, in Patients with Asthma. Am J Respir Crit Care Med, 2010, 181(8): 788-796. doi:10.1164/rccm.200909-1448OC. doi: 10.1164/rccm.200909-1448OC URL
[43]	Hanania NA, Korenblat P, Chapman KR, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA Ⅰ and LAVOLTA Ⅱ): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med, 2016, 4(10): 781-796. doi:10.1016/S2213-2600(16)30265-X. doi: 10.1016/S2213-2600(16)30265-X pmid: 27616196
[44]	Panettieri RA Jr, Sjöbring U, Péterffy A, et al. Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir Med, 2018, 6(7): 511-525. doi:10.1016/S2213-2600(18)30184-X. doi: 10.1016/S2213-2600(18)30184-X pmid: 29792288
[45]	Russell RJ, Chachi L, FitzGerald JM, et al. Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. Lancet Respir Med, 2018, 6(7): 499-510. doi:10.1016/S2213-2600(18)30201-7. doi: 10.1016/S2213-2600(18)30201-7 pmid: 29793857
[46]	Pepper AN, Renz H, Casale TB, et al. Biologic Therapy and Novel Molecular Targets of Severe Asthma. J Allergy Clin Immunol Pract, 2017, 5(4): 909-916. doi:10.1016/j.jaip.2017.04.038. doi: S2213-2198(17)30354-9 pmid: 28689841
[47]	Danso MO, van Drongelen V, Mulder A, et al. TNF-α and Th2 Cytokines Induce Atopic Dermatitis-Like Features on Epidermal Differentiation Proteins and Stratum Corneum Lipids in Human Skin Equivalents. J Invest Dermatol, 2014, 134(7): 1941-1950. doi:10.1038/jid.2014.83. doi: S0022-202X(15)36873-1 pmid: 24518171
[48]	Howell MD, Kim BE, Gao P, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol, 2009, 124(3): R7-R12. doi:10.1016/j.jaci.2009.07.012. doi: 10.1016/j.jaci.2009.07.012 URL
[49]	Furue M, Yamamura K, Kido-Nakahara M, et al. Emerging role of interleukin‐31 and interleukin‐ 31 receptor in pruritus in atopic dermatitis. Allergy, 2018, 73(1): 29-36. doi:10.1111/all.13239. doi: 10.1111/all.13239 pmid: 28670717
[50]	Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet, 2016, 388(10039): 31-44. doi:10.1016/S0140-6736(16)30307-5. doi: 10.1016/S0140-6736(16)30307-5 pmid: 27130691
[51]	Castro M, Corren J, Pavord ID, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med, 2018, 378(26): 2486-2496. doi:10.1056/NEJMoa1804092. doi: 10.1056/NEJMoa1804092 URL
[52]	Busse WW, Maspero JF, Rabe KF, et al. Liberty Asthma QUEST: Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate Dupilumab Efficacy/Safety in Patients with Uncontrolled, Moderate-to-Severe Asthma. Adv Ther, 2018, 35(5): 737-748. doi:10.1007/s12325-018-0702-4. doi: 10.1007/s12325-018-0702-4 pmid: 29725983
[53]	Simpson E, Udkoff J, Borok J, et al. Atopic dermatitis: emerging therapies. Semin Cutan Med Surg, 2017, 36(3): 124-130. doi:10.12788/j.sder.2017.0137. doi: 10.12788/j.sder.2017.0137 pmid: 28895959
[54]	Bachert C, Desrosiers M, Mullol J, et al. A Randomized Phase 3 Study, Sinus-52, Evaluating the Efficacy and Safety of Dupilumab in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol, 2019, 143(2): AB433. doi:10.1016/j.jaci.2018.12.980. doi: 10.1016/j.jaci.2018.12.980
[55]	Han JK, Bachert C, Desrosiers M, et al. Efficacy and Safety of Dupilumab in Patients with Chronic Rhinosinusitis with Nasal Polyps: Results from the Randomized Phase 3 Sinus-24 Study. J Allergy Clin Immunol, 2019, 143(2): AB422. doi:10.1016/j.jaci.2018.12.948. doi: 10.1016/j.jaci.2018.12.948
[56]	Ragnoli B, Morjaria J, Pignatti P, et al. Dupilumab and teze-pelumab in severe refractory asthma: new opportunities. Ther Adv Chronic Dis, 2022, 13:20406223221097327. doi:10.1177/20406223221097327. doi: 10.1177/20406223221097327
[57]	Wechsler ME, Ford LB, Maspero JF, et al. Long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma (TRAVERSE): an open-label extension study. Lancet Respir Med, 2022, 10(1): 11-25. doi:10.1016/S2213-2600(21)00322-2. doi: 10.1016/S2213-2600(21)00322-2 URL
[58]	Tollenaere MAX, Litman T, Moebus L, et al. Skin Barrier and Inflammation Genes Associated with Atopic Dermatitis are Regulated by Interleukin-13 and Modulated by Tralokinumab In vitro. Acta Derm Venereol, 2021, 101(4): adv00447. doi:10.2340/00015555-3810. doi: 10.2340/00015555-3810 URL
[59]	Wollenberg A, Weidinger S, Worm M, et al. Tralokinumab in atopic dermatitis. J Dtsch Dermatol Ges, 2021, 19(10): 1435-1442. doi:10.1111/ddg.14545. doi: 10.1111/ddg.14545 pmid: 34390128
[60]	European Medicines Agency. Adtralza (tralokinumab): assessment report[R/OL]. 2020. https://www.ema.europa.eu/en/documents/assessment-report/adtralza-h-c-5255-0000-epar-assessment-report_en.pdf.
[61]	Carlsson M, Braddock M, Li Y, et al. Evaluation of Antibody Properties and Clinically Relevant Immunogenicity, Anaphylaxis, and Hypersensitivity Reactions in Two Phase Ⅲ Trials of Tralokinumab in Severe, Uncontrolled Asthma. Drug Saf, 2019, 42(6): 769-784. doi:10.1007/s40264-018-00788-w. doi: 10.1007/s40264-018-00788-w
[62]	Diveu C, Lak-Hal AH, Froger J, et al. Predominant expression of the long isoform of GP130-like (GPL) receptor is required for interleukin-31 signaling. Eur Cytokine Netw, 2004, 15(4): 291-302. pmid: 15627637
[63]	Kabashima K, Matsumura T, Komazaki H, et al. Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus. N Engl J Med, 2020, 383(2): 141-150. doi:10.1056/NEJMoa1917006. doi: 10.1056/NEJMoa1917006 URL
[64]	Menzies-Gow A, Corren J, Bourdin A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med, 2021, 384(19): 1800-1809. doi:10.1056/NEJMoa2034975. doi: 10.1056/NEJMoa2034975 URL
[65]	Pelaia C, Pelaia G, Crimi C, et al. Tezepelumab: A Potential New Biological Therapy for Severe Refractory Asthma. Int J Mol Sci, 2021, 22(9):4369. doi:10.3390/ijms22094369. doi: 10.3390/ijms22094369 URL
[66]	Hoy SM. Tezepelumab: First Approval. Drugs, 2022, 82(4): 461-468. doi:10.1007/s40265-022-01679-2. doi: 10.1007/s40265-022-01679-2 pmid: 35184265
[67]	Corren J, Parnes JR, Wang L, et al. Tezepelumab in Adults with Uncontrolled Asthma. N Engl J Med, 2017, 377(10):936-946. doi:10.1056/NEJMoa1704064. doi: 10.1056/NEJMoa1704064 URL
[68]	Ando K, Fukuda Y, Tanaka A, et al. Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis. Cells, 2022, 11(5): 819. doi:10.3390/cells11050819. doi: 10.3390/cells11050819 URL
[69]	Bian S, Zhang P, Li L, et al. Anaphylaxis Associated With Allergen Specific Immunotherapy, Omalizumab, and Dupilumab: A Real World Study Based on the US Food and Drug Administration Adverse Event Reporting System. Front Pharmacol, 2021, 12: 767999. doi:10.3389/fphar.2021.767999. doi: 10.3389/fphar.2021.767999 URL
[70]	Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; et al. The diagnosis and management of anaphylaxis: An updated practice parameter. J Allergy Clin Immunol, 2005, 115(3): S483-S523. doi:10.1016/j.jaci.2005.01.010. doi: 10.1016/j.jaci.2005.01.010 URL
[71]	Simons FE. Anaphylaxis, killer allergy: Long-term management in the community. J Allergy Clin Immunol, 2006, 117(2): 367-377. doi:10.1016/j.jaci.2005.12.002. doi: 10.1016/j.jaci.2005.12.002 URL

在医院发生严重过敏反应后的管理措施^[70]	在家中发生严重过敏反应后的管理措施^[71]
立即采取措施	患者自我管理
评估呼吸及循环系统	根据症状体征及时应对
大腿外侧肌肉注射0.3mg肾上腺素	肾上腺素自动注射器
启动紧急医疗服务	严重过敏反应紧急行动计划(下载自 www.AAAAI.org)
将患者置于卧位并尽量抬高下肢
保持气道通畅
给予氧气
建立静脉通路并输注生理盐水
必要时沙丁胺醇雾化吸入
必要时辅助其他药物,如H1抗组胺药或全身糖皮质激素