Dupilumab
Dupilumab 是一种作用于 IL-4 受体α亚基的全人源性单克隆抗体。对于有嗜酸粒细胞升高并且联合使用 ICS 和 LABA 的中重度持续性哮喘患者,在停用 ICS 和 LABA 后,dupilumab 治疗与安慰剂相比能减少哮喘发作、改善肺功能,并降低 Th2 细胞相关的炎症标记物水平。[77]Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368:2455-2466.http://www.nejm.org/doi/full/10.1056/NEJMoa1304048#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/23688323?tool=bestpractice.com
Tralokinumab
Tralokinumab 是一种中和 IL-13 的免疫球蛋白 G4 人源性单克隆抗体。在一项尽管使用控制性药物仍未达到控制的成人中重度哮喘患者的Ⅱ期安慰剂对照临床试验中,tralokinumab 治疗与肺功能改善有关,但与根据问卷调查评估的哮喘控制无关。[78]Piper E, Brightling C, Niven R, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013;41:330-338.http://erj.ersjournals.com/content/41/2/330.longhttp://www.ncbi.nlm.nih.gov/pubmed/22743678?tool=bestpractice.com
美泊利单抗
IL-5 是 Th2 免疫反应的一部分,通过调节 IL-5 或许可以减轻哮喘的炎症和气道重塑。抗 IL-5(美泊利单抗)的Ⅲ期临床试验表明美泊利单抗能减少难治性嗜酸粒细胞性哮喘的急性发作与口服皮质类固醇的剂量。[79]Tourangeau LM, Kavanaugh A, Wasserman SI. The role of monoclonal antibodies in the treatment of severe asthma. Ther Adv Resp Dis. 2011;5:183-194.http://www.ncbi.nlm.nih.gov/pubmed/21393345?tool=bestpractice.com[80]Pavord ID, Korn S, Howarth P, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380:651-659.http://www.ncbi.nlm.nih.gov/pubmed/22901886?tool=bestpractice.com[81]Liu Y, Zhang S, Li DW, et al. Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials. PLoS One. 2013;8:e59872.http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0059872http://www.ncbi.nlm.nih.gov/pubmed/23544105?tool=bestpractice.com[82]Bel EH, Wenzel SE, Thompson PJ, et al; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014;371:1189-1197.http://www.nejm.org/doi/full/10.1056/NEJMoa1403291#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/25199060?tool=bestpractice.com[83]Ortega HG, Liu MC, Pavord ID, et al; MENSA Investigators. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014;371:1198-1207.http://www.nejm.org/doi/full/10.1056/NEJMoa1403290#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/25199059?tool=bestpractice.com [
]What are the benefits and harms of anti-IL-5 therapies for adults with asthma?https://cochranelibrary.com/cca/doi/10.1002/cca.1921/full显示答案
Reslizumab
Reslizumab 是一种人源化单克隆抗体,能与 IL-5 结合。 美国食品药品监督管理局 (FDA) 已批准其作为添加维持治疗,用于成人重度哮喘和嗜酸粒细胞表型患者。 [
]What are the benefits and harms of anti-IL-5 therapies for adults with asthma?https://cochranelibrary.com/cca/doi/10.1002/cca.1921/full显示答案
Lebrikizumab
已经发现 IL-13 存在于哮喘患者气道,并介导哮喘的多项特征,包括气道高反应性、炎症、黏膜上皮化生、气道成纤维细胞活化与增殖,这些都会导致有害的气道重塑。在一项尽管已经使用 ICS 与 LABA 治疗仍有症状的中度哮喘患者的临床试验中,抗 IL-13 抗体 lebrikizumab 治疗对所有患者的气道阻塞都有效。但是循环中 Th2 细胞标记蛋白-骨膜蛋白水平较高的患者比那些没有这种表型的患者的效果更好。[84]Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088-1098.http://www.nejm.org/doi/full/10.1056/NEJMoa1106469#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/21812663?tool=bestpractice.com
支气管热成型术
支气管热成型术是一种使用控制热能减少气道平滑肌的支气管镜手术。对于严重的哮喘患者,该手术通过减少哮喘重度急性发作、治疗后药物使用改善患者哮喘相关生活质量。然而,只有有限的专科治疗中心才能进行这项治疗。[85]Castro M, Rubin AS, Laviolette M, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med. 2010;181:116-124.http://www.atsjournals.org/doi/full/10.1164/rccm.200903-0354OC#.VBhPa_ldU9Ihttp://www.ncbi.nlm.nih.gov/pubmed/19815809?tool=bestpractice.com[86]National Institute for Health and Care Excellence. Bronchial thermoplasty for severe asthma. January 2012. http://www.nice.org.uk/ (last accessed 11 October 2016).http://www.nice.org.uk/guidance/IPG419[87]Wahidi MM, Kraft M. Bronchial thermoplasty for severe asthma. Am J Respir Crit Care Med. 2012;185:709-714.http://www.atsjournals.org/doi/full/10.1164/rccm.201105-0883CI#.UqrpbNl3MYshttp://www.ncbi.nlm.nih.gov/pubmed/22077066?tool=bestpractice.com[88]Torrego A, Solà I, Munoz AM, et al. Bronchial thermoplasty for moderate or severe persistent asthma in adults. Cochrane Database Syst Rev. 2014;(3):CD009910.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009910.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24585221?tool=bestpractice.com