变应原免疫治疗进展

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,变应原免疫治疗进展,变应性疾病,-,如影相随,Gupta R, et al. BMJ. 2003 Nov 15x;327(7424):1142-3,Ninan TK, et al.,BMJ. 1992 Apr 4;304(6831):873-5,历史变迁,Larch M, et al. Nat Rev Immunol. 2006;6(10):761-71,Von Pirquet,是,Specific Immunotherapy (SIT),还是,Allergen Immunotherapy (AIT)?,Caldern MA, et al. Allergy. 2013;68(7):825-8,AIT,的机制是什么？,Akdis CA, et al. World Allergy Organ J. 2015;8(17): 1-12.,Mechanisms of allergen-specific immunotherapy and immune tolerance to allergens.,Very early basophil tolerance :,Early decrease in mast cell and basophil activity for systemic anaphylaxis,Type I skin test reactivity,Early increase in specific IgE followed by a late decrease in specific IgE,Increase in specific IgG4 and in some studies IgA and IgG1,Decreased numbers of tissue mast cells and eosinophils and release of their mediators in nasal mucosal biopsies of allergic rhinitis patients,Decreased skin late-phase response in parallel to decreased lymphocyte and eosinophil infiltration,Induction of Treg and Breg cells suppression of Th2-Th1 cells,AIT,可能的推手,-,Treg,和,Breg,Akdis CA, et al. World Allergy Organ J. 2015;8(17): 1-12.,Mechanisms of allergen-specific immunotherapy and,immune,tolerance to allergens.,Pharmacotherapy,Allergen avoidance,Allergen immunotherapy,Patient education,变应性疾病综合治疗方案,Bousquet J, et al. J Allergy Clin Immunol. 1998;102(4 Pt 1):558-62,Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper.,内容,建议,推荐强度,环境因素,那些明确因环境变应原致病的患者应避免接触已知变应原或进行环境控制（不养宠物、使用过滤系统、防螨罩或杀螨剂）,可选,Seidman MD, et al. Otolaryngol Head Neck Surg. 2015;152(1 Suppl):S1-43,GINA,和,NAEPP,关于环境控制的建议,GINA 2014,N Engl Med 2009; 360:1862-9,AIT,对蜂毒过敏反应、过敏性鼻炎,/,结膜炎，过敏性哮喘有效,免疫治疗是唯一可以影响变应性疾病自然病程的治疗方法，它还可阻止变应性鼻炎发展为哮喘,成功的免疫治疗取决于标准化的、可持续生产的高质量变应原疫苗,Bousquet J, et al. J Allergy Clin Immunol. 1998;102(4 Pt 1):558-62,10,2006,2011,2012,欧美,AIT,现状,Burks AW, et al. J Allergy Clin Immunol. 2013;131(5):1288-96,变应原配方,疗效：由于研究设计的多样性，使得比较困难,总结：只给患者接种引起症状的变应原,Nelson HS et al. J Allergy Clin Immunol. 2009; 123: 763-769,脱敏途径,-SCIT,或,SLIT,欧洲：,SLIT,占,AIT,的,45%,，区域差别大（北欧限新,EMA,注册变应原，德国,25%,，南欧,80%,）,美国：,2014,年,4,月,FDA,批准,3,种舌下片剂,传统治疗：,SCIT,对,AIT,疗效的共识,-,过敏性疾病修饰剂,Committee for Medicinal Products for Human Use (CHMP) and Efficacy Working Party (EWP),预防变应性鼻炎并发哮喘,预防对新变应原过敏,停用后保持长期临床效果,真实世界,AIT,对预防鼻炎进展为哮喘的肯定作用,-6,年回顾性研究,Schmitt J, et al. J Allergy Clin Immunol. 2015 Dec;136(6):1511-6,RA,患者进行,AIT,发生哮喘的危险显著低于非,AIT,SCIT,的预防作用显著,天然提取物制备的变应原作用显著,3,年和更久的治疗作用显著,对,AIT,现状的共识,-,适应症,适应症：同时罹患哮喘和鼻炎,变应性鼻炎,药物不能控制症状,严重药物不良反应,不愿长期用药,对,AIT,现状的共识,-,操作指南,适应症,禁忌症,治疗,后,观察,30mins,妊娠期,AIT,-,阻滞剂的使用,人员培训,医疗器械准备,医疗文件准备,对,AIT,现状的共识,-,低估,AIT,的治疗价值,尽管均认为,AIT,是唯一对哮喘和鼻炎起到修饰作用的治疗，目前仅,5%,患者接受,AIT,疗效证据不充分,支出,-,获益比不明确,从业医生水准和认知水平不一,普通人群对,AIT,常识少,患者害怕治疗方案或药品申请过程,入选病例的差异,(,level,D) -GINA 2015,Jutel M, et al. J Allergy Clin Immunol. 2015;136(3):556-68,未来关注,研究标准化,Canonica GW,et al. Allergy. 2007;62(3):317-24Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce,1911,年,SCIT,首次应用于临床，,1960,年发表首个双盲安慰剂对照（,DBPC,）疗效观察的临床研究，,SLIT,的,DBPC,在,1986,年。,方法学缺陷：样本小,退出率高,组间疾病严重程度不匹配,变应原效价无法比较,单独症状评价或用药评分,William Frankland (1912-) AIT 100,年纪念,变应原标准化,美国,FDA,生物检测研究中心,CBER(center for biologics evaluation and research),标准化和非标准化制剂,欧洲,欧洲药物局（,EMA,）统一审查认证,变应原工业化生产，新产品进行注册,Jutel M, et al. J Allergy Clin Immunol. 2015;136(3):556-68,Cox L, et al. J Allergy Clin Immunol. 2011;127(1 Suppl):S1-55,Wheatley LM, et al. N Engl J Med. 2015 Jan 29;372(5):456-63,单一变应原效果肯定,It is not know whether multi-allergen therapy results in better outcomes than single-allergen therapy. Althrough some older studies suggest a benefit of multi-allergen immunotherapy,most trails showing the efficacy of immunotherapy involve a signle allergen,.,-Clinical practice. Allergic rhinitis,-Allergen immunotherapy: a practice parameter third update,Summary Statement 72: There are few studies that investigated the efficacy of multiallergen subcutaneous immunotherapy.,These studies have produced conflicting results, with some demonstrating significant clinical improvement compared with placebo and others showing no benefit over optimal pharmacotherapy and environmental control measures.,Thus it is important to treat the patients only with relevant allergens. ( B ),变应原种类：强调使用主要变应原,AIT,的安全性,SCIT:,注射部位充血、肿胀、瘙痒（,85%,）,全身反应：,1,次注射,致命过敏反应：,1/100,万次注射,SLIT,：口咽瘙痒、肿胀（,75%,）,无致命过敏反应,Wheatley LM, et al.,Clinical practice. Allergic rhinitis.,N Engl J Med. 2015; 372(5): 456-63,减少,SCIT,风险,Epstein TG. J Allergy Clin Immunol Pract. 2014 ;2(2):161-7.,哮喘未控制、重症哮喘是导致严重不良反应的主要原因,措施,1,每次治疗前进行哮喘控制评估,2,遵循,标准操作规范,3,花粉季调整剂量,4,避免集群免疫治疗,分子诊断技术的应用,Molecular-based allergy (MA) diagnostics,鉴别多重过敏患者真正的致敏源,真正的变应原,vs,交联反应 （泛变应原）,减少食物过敏诊断的风险,稳定的变应原分子,vs,易变的变应原分子,可能提高,AIT,的疗效,Canonica GW, et al. World Allergy Organ J. 2013 Oct 3;6(1):17.,A WAO - ARIA - GALEN consensus document on molecular-based allergy diagnostics.,AIT,在个体化治疗中的作用,AIT,现状综合评价,-SWOT,Jutel M, et al. J Allergy Clin Immunol. 2015;136(3):556-68,Strengh Weakness Opportunity Threats,谢 谢！,谢谢大家！,