生物制剂治疗支气管哮喘的研究进展

doi:10.6040/j.issn.1673-3770.1.2018.040

摘要/Abstract

摘要：

支气管哮喘是呼吸系统常见的气道慢性炎症性疾病，吸入皮质激素是其主要治疗策略。随着哮喘发病机制的深入研究，发现气道炎症类型不同，吸入激素治疗的反应不同。针对气道炎症反应过程中的炎性介质，已经开发了多种生物制剂。临床随机对照研究中，严重嗜酸粒细胞性哮喘患者从中获益，部分临床疗效存在争议。儿童用药的疗效和安全性及药物对疾病产生的长期影响还需进一步研究证实。

关键词: 哮喘, 气道炎症, 生物制剂治疗

Abstract:

Bronchial asthma is a common chronic airway inflammatory disease of the respiratory system. Inhaled corticosteroids are the primary treatment strategy. Studies have shown that the clinical response to inhaled corticosteroids varies due to different types of airway inflammation. A variety of biological agents aimed at inflammatory mediators in airway inflammation have been developed. Randomized controlled trials of these agents have shown that patients with severe eosinophilic asthma benefit from therapy, but controversy remains regarding some aspects of their clinical effects. Their efficacy and safety in children, as well as their long-term effects on disease course and progression need further study and confirmation.

Key words: Asthma, Airway inflammation, Biologic therapy

中图分类号:

R562.2

沙莉,刘传合. 生物制剂治疗支气管哮喘的研究进展[J]. 山东大学耳鼻喉眼学报, 2019, 33(1): 53-58.

Li SHA,Chuanhe LIU. Research progress in the treatment of bronchial asthma with biological agents[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(1): 53-58.

参考文献 33

1	Paul WE , Zhu JF . How are T(H)2-type immune responses initiated and amplified?[J]. Nat Rev Immunol, 2010, 10 (4): 225- 235. doi: 10.1038/nri2735
2	Harper RW , Zeki AA . Immunobiology of the critical asthma syndrome[J]. Clin Rev Allergy Immunol, 2015, 48 (1): 54- 65. doi: 10.1007/s12016-013-8407-6
3	Dunn RM , Wechsler ME . Anti-interleukin therapy in asthma[J]. Clin Pharmacol Ther, 2015, 97 (1): 55- 65. doi: 10.1002/cpt.11
4	Kearley J , Erjefalt JS , Andersson C , et al. IL-9 governs allergen-induced mast cell numbers in the lung and chronic remodeling of the airways[J]. Am J Respir Crit Care Med, 2011, 183 (7): 865- 875. doi: 10.1164/rccm.200909-1462OC
5	Moro K , Yamada T , Tanabe M , et al. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells[J]. Nature, 2010, 463 (7280): 540- 544. doi: 10.1038/nature08636
6	Christianson CA , Goplen NP , Zafar I , et al. Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33[J]. J Allergy Clin Immunol, 2015, 136 (1): 59- 68.e14. doi: 10.1016/j.jaci.2014.11.037
7	Normansell R , Walker S , Milan SJ , et al. Omalizumab for asthma in adults and children[J]. Cochrane Database Syst Rev, 2014, (1): CD003559. doi: 10.1002/14651858.CD003559.pub4
8	Storms W , Bowdish MS , Farrar JR . Omalizumab and asthma control in patients with moderate-to-severe allergic asthma: a 6-year pragmatic data review[J]. Allergy Asthma Proc, 2012, 33 (2): 172- 177. doi: 10.2500/aap.2012.33.3527
9	Long AD , Rahmaoui A , Rothman KJ , et al. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab[J]. J Allergy Clin Immunol, 2014, 134 (3): 560- 567.e4. doi: 10.1016/j.jaci.2014.02.007
10	Gauvreau GM , Arm JP , Boulet LP , et al. Efficacy and safety of multiple doses of QGE031 (ligelizumab) versus omalizumab and placebo in inhibiting allergen-induced early asthmatic responses[J]. J Allergy Clin Immunol, 2016, 138 (4): 1051- 1059. doi: 10.1016/j.jaci.2016.02.027
11	Bel EH , Wenzel SE , Thompsen PJ , et al. Oral glucocorticoidsparing effect of mepolizumab in eosinophilic asthma[J]. N Ensl Jmed, 2014, 371 (13): 1189- 1197. doi: 10.1056/NEJMoa1403291
12	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[J]. The Lancet Respiratory Medicine, 2015, 3 (5): 355- 366. doi: 10.1016/S2213-2600(15)00042-9
13	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[J]. The Lancet, 2016, 388 (10056): 2128- 2141. doi: 10.1016/S0140-6736(16)31322-8
14	Antoniu SA , Cojocaru I . Pitrakinra for asthma[J]. Expert Opin Biol Ther, 2010, 10 (11): 1609- 1615. doi: 10.1517/14712598.2010.524203
15	Wenzel S , Wilbraham D , Fuller R , et al. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies[J]. Lancet, 2007, 370 (9596): 1422- 1431. doi: 10.1016/S0140-6736(07)61600-6
16	Slager RE , Otulana BA , Hawkins GA , et al. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor α antagonist[J]. J Allergy Clin Immunol, 2012, 130 (2): 516- 522.e4. doi: 10.1016/j.jaci.2012.03.030
17	Vatrella A , Fabozzi I , Calabrese C , et al. Dupilumab: a novel treatment for asthma[J]. J Asthma Allergy, 2014, 7: 123- 130. doi: 10.2147/JAA.S52387
18	Castro M , Corren J , Pavord ID , et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma[J]. N Engl J Med, 2018, 378 (26): 2486- 2496. doi: 10.1056/NEJMoa1804092
19	Zayed Y , Kheiri B , Banifadel M , et al. Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials[J]. J Asthma, 2018, 1- 10. doi: 10.1080/02770903.2018.1520865
20	Corren J , Lemanske RF , Hanania NA , et al. Lebrikizumab treatment in adults with asthma[J]. N Engl J Med, 2011, 365 (12): 1088- 1098. doi: 10.1056/NEJMoa1106469
21	Piper E , Brightling C , Niven R , et al. A phase Ⅱ placebo-controlled study of tralokinumab in moderate-to-severe asthma[J]. Eur Respir J, 2013, 41 (2): 330- 338. doi: 10.1183/09031936.00223411
22	Brightling CE , Chanez P , Leigh R , et al. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial[J]. Lancet Respir Med, 2015, 3 (9): 692- 701. doi: 10.1016/S2213-2600(15)00197-6
23	Corren J , Parnes JR , Wang LW , et al. Tezepelumab in adults with uncontrolled asthma[J]. N Engl J Med, 2017, 377 (10): 936- 946. doi: 10.1056/NEJMoa1704064
24	Kirsten A , Watz H , Pedersen F , et al. The anti-IL-17A antibody secukinumab does not attenuate ozone-induced airway neutrophilia in healthy volunteers[J]. Eur Respir J, 2013, 41 (1): 239- 241. doi: 10.1183/09031936.00123612
25	Busse WW , Holgate S , Kerwin E , et al. Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma[J]. Am J Respir Crit Care Med, 2013, 188 (11): 1294- 1302. doi: 10.1164/rccm.201212-2318OC
26	O′Byrne PM , Metev H , Puu M , et al. Efficacy and safety of a CXCR2 antagonist, AZD5069, in patients with uncontrolled persistent asthma: a randomised, double-blind, placebo-controlled trial[J]. Lancet Respir Med, 2016, 4 (10): 797- 806. doi: 10.1016/S2213-2600(16)30227-2
27	Watz H , Uddin M , Pedersen F , et al. Effects of the CXCR2 antagonist AZD5069 on lung neutrophil recruitment in asthma[J]. Pulm Pharmacol Ther, 2017, 45: 121- 123. doi: 10.1016/j.pupt.2017.05.012
28	Berry MA , Hargadon B , Shelley M , et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma[J]. N Engl J Med, 2006, 354 (7): 697- 708. doi: 10.1056/NEJMoa050580
29	Howarth PH , Babu KS , Arshad HS , et al. Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma[J]. Thorax, 2005, 60 (12): 1012- 1018. doi: 10.1136/thx.2005.045260
30	Erin EM , Leaker BR , Nicholson GC , et al. The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma[J]. Am J Respir Crit Care Med, 2006, 174 (7): 753- 762. doi: 10.1164/rccm.200601-072OC
31	Taille C . Monoclonal anti-TNF-α antibodies for severe steroid-dependent asthma: a case series[J]. TORMJ, 2013, 7 (1): 21- 25. doi: 10.2174/1874306401307010021
32	Rouhani FN , Meitin CA , Kaler M , et al. Effect of tumor necrosis factor antagonism on allergen-mediated asthmatic airway inflammation[J]. Respir Med, 2005, 99 (9): 1175- 1182. doi: 10.1016/j.rmed.2005.02.031
33	Morjaria JB , Chauhan AJ , Babu KS , et al. The role of a soluble TNFalpha receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial[J]. Thorax, 2008, 63 (7): 584- 591. doi: 10.1136/thx.2007.086314

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