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Advances in the treatment of allergic rhinitis 变应性鼻炎的治疗进展,Dr Warner Carr MD,Burden of allergic rhinitis AR对患者及社会造成的严重负担,Allergic rhinitis (AR) occurs in over 500 million people around the world1 （全球约有5亿变应性鼻炎患者） The effects of AR are underestimated （AR的影响被低估） Symptomatic burden2（症状困扰） Reduces patient quality of life3（降低患者生活质量） Impairs school and work performance4,5（导致患者工作和学习成绩下降） AR is a costly disease（经济负担） 4260/patient/year in Europe6 （欧洲，4260/患者/年） 3.4 billion US$ annually in the United States in direct medical costs alone.7（美国每年直接医疗费用一项约为34亿美元）,1. Bousquet et al, Allergy 2008;63:8-160. 2. Meltzer et al, JACI 2009; 124:S43-70. 3. Canonica et al, Allergy 2007;62:17-25. 4. Walket et al, JACI 2007;120:381-7. 5. Vandenplas et al Curr Opin Allergy Clin Immunol 2008;8:145-9. 6. Bousquet et al Allergy 2005;60:788-94. 7. Meltzer 106:S12-6.,Allergic Rhinitis: Affects Quality of Life 生活质量影响,1. AAAAI. The Allergy Report 2000. . 2. Spector SL. J Allergy Clin Immunol 1997;99:S773-80. 3. Ker 63:8-160. AR: allergic rhinitis,Common Comorbidities1,2（AR常见合并症）,Important to treat allergic rhinitis effectively from the start 早期有效治疗变应性鼻炎至关重要！,Allergic march: AR can progress to asthma.3 变应性进程：AR可进一步发展为哮喘。 AR and non-AR negatively impact on asthma control and patient quality of life .4,5 变应性鼻炎和非变应性鼻炎不利于控制 哮喘，同时降低患者生活质量 Patients treated for AR have a significantly lower risk of subsequent asthma-related events.6 AR治疗患者的后续哮喘相关性事件的危险 性显著降低,AR: allergic rhinitis,ARIA guidelines. Bousquet et al, Allergy 2008; 63: 8-160,Treatment of allergic rhinitis ARIA AR的治疗ARIA,ARIA update Recommendation 14,Should intranasal H1-antihistamines be used for treatment of allergic rhinitis? (鼻内组胺H1受体拮抗剂应该用来治疗AR吗？) We suggest intranasal H1-antihistamines in adults with seasonal allergic rhinitis and in children with seasonal allergic rhinitis. 建议患SAR的成人和儿童使用鼻内组胺H1受体拮抗剂。 In adults and children with persistent allergic rhinitis, we suggest that clinicians do not administer and patients do not use intranasal H1-antihistamines until more data on their relative efficacy and safety are available. 对于患PAR的成人和儿童，在获得更多的组胺H1受体拮抗剂相对有效性及安全性的数据之前，建议临床医师不要给予，患者也不要使用鼻内组胺H1受体拮抗剂。,ARIA guidelines update. Brozek et al, JACI 2010;126: 466-76,Joint Task Force Practice Parameters for Allergic Rhinitis Treatment特别工作小组关于AR的诊疗指南 Strength of these guidelines 指南的优点,Allergic rhinitis is one of the most common conditions seen by US health professionals（AR是美国临床医师最常见的疾病之一） Guidelines based on this wealth of clinical experience （指南基于大量临床经验） Evidence-based（循证医学证据） Based on an extensive review of the literature（基于大量文献综述） Evidence subjected to an intensive review process（证据经集中审查） Developed with support and guidance of the AAAAI and the ACAAI. （在AAAAI和ACAAI的支持和指导下）,Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,AAAAI: American Academy of Allergy, Asthma & Immunology 美国变态反应、哮喘和免疫学会 ACAAI: American College of Allergy, Asthma and Immunology美国变态反应、现场和免疫学院,Classification of recommendations and evidence Category of evidence 证据分类和推荐强度分级 Ia. Evidence from meta-analysis of randomized controlled trials Ib. Evidence from at least 1 randomized controlled trial IIa. Evidence from at least 1 controlled study without randomization IIb. Evidence from at least 1 other type of quasi-experimentalstudy III. Evidence from nonexperimental descriptive studies, such as comparative studies,Joint Task Force Practice Parameters for Allergic Rhinitis Treatment 特别工作小组关于AR的诊疗指南,Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,Intranasal antihistamines 鼻喷抗组胺药 65. Intranasal antihistamines may be considered for use as first line treatment for allergic and nonallergic rhinitis. A 鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物。A级证据 66. Intranasal antihistamines are efficacious and equal to or superior to oral second-generation antihistamines for treatment of seasonal allergic rhinitis. A 在SAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药。 A级证据,Joint Task Force Practice Parameters for Allergic Rhinitis Treatment AR诊疗指南 Role of intranasal antihistamines 鼻喷抗组胺药的地位,Joint Task Force Practice Parameters for Allergic Rhinitis Treatment AR诊疗指南 Role of intranasal antihistamines 鼻喷抗组胺药的地位,Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,67. Because systemic absorption occurs, currently available intranasal antihistamines have been associated with sedation and can inhibit skin test reactions. A 因存在全身吸收，目前市场上的鼻喷抗组胺药可能存在镇静作用， 抑制皮肤反应。 A级证据 68. Intranasal antihistamines have been associated with a clinically significant effect on nasal congestion. A 鼻喷抗组胺药对鼻塞有显著临床效果。A级证据 69. Intranasal antihistamines are generally less effective than intranasal corticosteroids for treatment of allergic rhinitis. A 鼻喷抗组胺药疗效略逊于鼻喷激素。A级证据,Advantages of topical application 局部给药的优势,Drug is delivered directly to the site of inflammation where it is needed most. 药物直达病变部位 Rapid onset of action 起效快 Compared with systemic treatments, higher concentrations can be applied topically 与全身治疗相比，局部药物浓度更高 Enhanced therapeutic effects 疗效更强 Risk of interaction with concomitant medication is reduced 降低药物相互作用的风险 Potential for systemic adverse events is minimized 使全身给药潜在的不良反应最小化,Mode of action 作用机制,Intranasal antihistamines may be considered for use as first-line treatment for allergic and non-allergic rhinitis1 鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物,Azelastine has a triple mode of actionMORE than an antihistamine 爱赛平有独特三重作用机制，不仅仅是一种抗组胺药,1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,Antihistaminic 抗组胺作用 Anti-inflammatory 抗炎作用 Mast cell stabilizing 稳定肥大细胞,Intranasal antihistamines may be considered for use as first-line treatment for allergic and non-allergic rhinitis1 鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物 Efficacy of Azelastine in all forms of allergic rhinitis2 爱赛平对各种AR的疗效,Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84. Lieberman P et al. Curr Med Res Opin 2005;21:611-18,TNSS: Total Nasal Symptom Score; SAR: Seasonal Allergic Rhinitis,1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,爱赛平改善SAR症状：起效快,Intranasal antihistamines may be considered for use as first-line treatment for allergic and non-allergic rhinitis1 鼻喷抗组胺药作为变应性和非变应性鼻炎的一线治疗药物,Meta-analyses have shown nasal antihistamines to yield lower number need to treat values than oral antihistamines.2,3 Meta-分析显示鼻喷抗组胺药的NNT值（需要治疗的患 者数）比口服抗组胺药的更低 Effective in patients who do not respond to oral-antihistamines, 对口服抗组胺药治疗无效的患者有效,1. Wallace et al, JACI;2008;122:S1-S84. 2. Lee 4:429-46,66. Intranasal antihistamines are efficacious and equal to or superior to oral second-generation antihistamines for treatment of seasonal allergic rhinitis. A 在SAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代 口服抗组胺药。,Favours azelastine2,Favours oral antihistamines,1. Wallace et al, JACI 2008;122:S1-S84. 2. Lee SAR: seasonal allergic rhinitis,Intranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在SAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药,Azelastine: 2 sprays/nostril bd,1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84. TNSS: Total Nasal Symptom Score,Intranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在SAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药,RQLQ: rhinitis quality of life questionnaire; SAR: Seasonal Allergic Rhinitis,Azelastine: 2 sprays/nostril bd,1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,Intranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在SAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药,Azelastine Nasal Spray in patients with unsatisfactory response to oral antihistamines2 爱赛平对于口抗组胺药效果不理想患者,Oral Antihistamines 口服抗阻胺药 NON RESPONDER 无反应者,20% of patients do not respond to oral antihistamines These patients do respond to intranasal azelastine,1. Wallace et al, JACI 2008;122:S1-S84 2. Berger et al, Ann Allergy Asthma Immunol 2003;91(2):205-11 SAR: Seasonal allergic rhinitis,Intranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在SAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药,TNSS: Total Nasal Symptom Score,Azelastine: 2 sprays/nostril bd,1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,Intranasal antihistamines are superior to oral second-generation antihistamines for treatment of SAR1 在SAR治疗中，鼻喷抗组胺药的疗效等同甚至优于第二代口服抗组胺药,Joint Task Force Practice Parameters for Allergic Rhinitis Treatment AR诊疗指南 Role of intranasal antihistamines 鼻喷抗组胺药的地位,Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,67. Because systemic absorption occurs, currently available intranasal antihistamines have been associated with sedation and can inhibit skin test reactions. A 因存在全身吸收，目前市场上的鼻喷抗组胺药可能存在镇静作用， 抑制皮肤反应。 A级证据 68. Intranasal antihistamines have been associated with a clinically significant effect on nasal congestion. A 鼻喷抗组胺药对鼻塞有显著临床效果。A级证据 69. Intranasal antihistamines are generally less effective than intranasal corticosteroids for treatment of allergic rhinitis. A 鼻喷抗组胺药疗效略逊于鼻喷激素。A级证据,Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81,N=306,1. Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,Intranasal antihistamines have been associated with a clinically significant effect on nasal congestion1 鼻喷抗组胺药对鼻塞有显著临床效果,Very difficult to avoid certain allergens 一些过敏原很难避免 Many patients do not respond sufficiently to treatment. 许多患者对治疗效果不满意 Disease severity is frequently under-estimated, and consequently inadequately treated.1 疾病的严重程度被低估，导致治疗不充分 Most patients suffer from moderate-to-severe disease.2 大多数患者为中重度变应性鼻炎 Patients frequently experience severe symptoms while on therapy, and are dissatisfied and non-compliant with currently available therapy.3,4患者在治疗情况下症状仍很严重，对现有治疗不满意、依从性不高 As many as 74.4% of patients use multiple therapies to achieve symptom control.5 74.4%进行联合治疗的患者症状得到控制,1. Maurer 57:546-54.,Challenges for allergic rhinitis therapy （AR治疗的挑战） Combination therapy is the way forward（联合治疗是未来发展方向）,1. Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81:478-518. 2. Settipane RA. Allergy and Asthma Proc 2001; 22:185-189. 3. Mosges 62(9):969-75.,N=975,A high proportion of patients have mixed rhinitis1,2 很大比例患者是混合性鼻炎 Seasonal allergies 季节性过敏 Sensitivity to non-allergic triggers (environmental irritants) 对非过敏性激发物过敏（环境刺激物） Many allergic rhinitis patients are sensitized to multiple-triggers.许多AR患者对多种激发物过敏 Changes in lifestyle has led to: 生活方式改变导致 Perennial exposure to indoor allergens 常年暴露于室内变应原 Changes in sensitization patterns 致敏模式改变 Polysensitization to a variety of novel cross-reacting food and pet allergens.3 对一些新型相互作用的食物和宠物过敏原多重过敏,Challenges for allergic rhinitis therapy （AR治疗的挑战） Combination therapy is the way forward（联合治疗是未来发展方向）,Joint Task Force Practice Parameters for Allergic Rhinitis Treatment Step up/Step down approach 逐渐增加治疗药物/减少治疗药物的策略,Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84.,Joint Task Force Practice Parameters for Allergic Rhinitis Treatment AR诊疗指南,Wallace DV et al. J Allergy Clin Immunol. 2008;122(2 Suppl):S1-S84. SAR: seasonal allergic rhinitis; PAR: perennial allergic rhinitis; PRN: as needed,Effective management of allergic rhinitis may require combinations of medications. 有效治疗AR需要联合使用多种药物 Several studies have examined the benefit of combining a nasal steroid with an oral antihistamine or leukotriene antagonist in rhinitis1-7许多研究考察鼻喷激素联合口服抗组胺药物或 口服白三烯拮抗剂的疗效 Beclomethasone + astemizole Budesonide + terfenadine Flunisolide + terfenadine Fluticasone + loratadine /terfenadine/levocetirizine/cetirizine Fluticasone + montelukast None concluded that the combination was better than the nasal steroid alone 没有一项研究证明联合使用能优于单独使用鼻喷激素,Juniper EF, et al. J Allergy Clin Immunol. 1989;83:627-633. Ratner PH, et al. J Fam Pract. 1998;47:118-125. Simpson RJ. Ann Allergy. 1994;73:497-502. Backhouse CI, et al. J Int Med Res. 1986;14:35-41.,5. Juniper EF, et al. CMAJ. 1997;156:1123-1131. 6. Barnes ML, et al. Clin Exp Allergy. 2006;36:676-684. 7. Di Lorenzo G, et al. Clin Exp Allergy. 2004;34:259-267.,Combination Trials: Lack of Additive Benefit 激素联合口服抗组胺药未见增加疗效,Combination therapy: the way forward 联合治疗：未来发展方向,Objective: To determine, if greater efficacy could be achieved with Azelastine nasal spray plus Fluticasone nasal spray versus both treatments alone in the treatment of allergic rhinitis,试验目的: 确定联合使用氮卓斯汀鼻喷剂氟替卡松鼻喷剂与各自单独使用治疗变应性鼻炎疗效的比较,Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81,Combination therapy with azelastine NS and fluticasone propionate NS in the treatment of patients with SAR 爱赛平和苯丙酸氟替卡松鼻喷剂联合治疗SAR患者,Study Design 试验设计 Randomized, double-blind, parallel-group 随机、双盲、平行组 conducted during the 2005/2006 allergy season 在2005/2006年过敏性季节期间，5个中心进行 Primary efficacy variable 主要疗效参数 Change from baseline to day 14 in the total nasal symptom score (TNSS) 治疗14天后，TNSS较基线的改善 TNSS = sneezing, itchy nose, rhinorrhea and congestion TNSS= 喷嚏、鼻痒、流涕、鼻塞,Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81 NS: nasal spray; SAR: seasonal allergic rhinitis,Randomization and Treatment Groups随机化和分组情况 Azelastine 2 sprays/nostril bd Fluticasone 2 sprays/nostril qd,Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81 TNSS: Total Nasal Symptom Score; bd: twice daily; qd: once daily,Combination therapy the way forward联合治疗：未来发展方向 Azelastine plus Fluticasone: Percentage Improvement in TNSS 爱赛平联合氟替卡松：TNSS改善百分比,Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81; TNSS: Total Nasal Symptom Score,Azelastine and Fluticasone nasal sprays in combination deliver the greatest benefit 爱赛平联合氟替卡松治疗AR提高40%疗效,Combination therapy the way forward 联合治疗：未来发展方向 Azelastine plus Fluticasone: Rapid onset of action and sustained symptom improvement 爱赛平联合氟替卡松：起效快、症状改善作用持续,40% more improvement than fluticasone alone 与氟替卡松比较，联合治疗TNSS平均改善提高40%,Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81 TNSS: Total Nasal Symptom Score,Combination therapy the way forward联合治疗：未来发展方向 Azelastine plus Fluticasone: Percentage Improvement in Nasal Itch & congestion 爱赛平联合氟替卡松：Nasal Itch & Nasal congestion 改善百分比,Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81 Data presented as Least Square Mean for 14 Study Days,56% more relief from nasal itching and 48% more relief from nasal congestion vs fluticasone 与氟替卡松相比，联合治疗鼻痒改善增加56%，鼻塞改善增加48%,Combination therapy the way forward 联合治疗：未来发展方向 Azelastine plus Fluticasone: Percentage Improvement in Runny Nose & Sneezing 爱赛平联合氟替卡松：Runny Nose & Sneezing 改善百分比,Runny nose 流涕,Sneezing 喷嚏,58% improvement relative to fluticasone,46 % improvement relative to fluticasone,* p=0.05 vs azelastine,* p=0.04 vs fluticasone,*,*,Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81 Data presented as Least Square Mean for 14 Study Days,58% more relief from runny nose and 46% more relief from nasal sneezing vs fluticasone 与氟替卡松相比，联合治疗时流涕改善增加56%，喷嚏改善增加48%,No other AE was reported by more than one patient in any treatment group 在各治疗组中没有患者报道除上述以外的不良事件 No discontinuations dues to AEs 没有因不良事件而中止治疗,Combination therapy: the way forward 联合治疗：未来发展方向 Safety Information: Most common adverse events (AEs) 安全性信息：常见不良事件（AEs）,Ratner P, et al. Ann Allergy Asthma Immunol 2008;100:74-81,Combination therapy: the way forward 联合治疗：未来发展方向 Ratner et al Study Conclusions 研究结论,Azelastine in combination with fluticasone provided 爱赛平和氟替卡松联合治疗 40% more relief from overall nasal symptoms than fluticasone 与氟替卡松相比，鼻部症状总评分改善增加40% 56% more relief from nasal itching than fluticasone鼻痒改善增加56% 48% more relief from nasal congestion than fluticasone鼻塞改善增加48% 58% more relief from runny nose than fluticasone 流涕改善增加58% 46% more relief from sneezing than f