医学交流课件：治疗策略对哮喘控制的影响

1、治疗策略对哮喘控制的影响 仅供医疗专业人士进行医学科学交流，不可用于推广目的 大纲 哮喘控制不佳的原因 哮喘是一个炎症和症状波动的疾病 维持缓解治疗 哮喘全面控制哮喘全面控制: : 当前当前控制和未来控制和未来风险风险 GINA 指南指出哮喘控制包括当前控制和未来风险两个方面 1 GINA, Global Initiative for Asthma. 1. GINA. Global strategy for asthma management and prevention, 2012. Available at: /uploads/users/fi

2、les/GINA_Report_2012.pdf; 2. Bateman E et al. J Allergy Clin Immunol 2010; 125: 6008. 2 AIREAIRE研究：真研究：真实实世界哮喘患者世界哮喘患者ICSICS使用不足和使用不足和过过度使用度使用 AIRE研究显示： 使用ICS+SABA或ICS/LABA+ SABA治疗的哮喘患者入组研究前一 个月内缓解药（SABA）使用频次超过抗炎药物（ICS，ICS/LABA的3倍 AIRE, Asthma Insights and Reality in Europe; ICS, inhaled corticoster

3、oid; LABA, long-acting 2-agonist; SABA, short-acting 2-agonist. Rabe KF et al. Eur Respir J 2000; 16: 8027. Patients using medication Patients using medication (%)(%) 过过度度SABASABA吸入及吸入及ICSICS使用不足使用不足导导致哮喘相关死亡率升高致哮喘相关死亡率升高 在控制药物使用不足的情况下过分依赖缓解药（SABA）与哮喘相关死亡率相关 ICS, inhaled corticosteroid; SABA, short-

4、acting 2-agonist. 1. Suissa S et al. New Engl J Med 2000; 343: 3326; 2. Suissa S et al. Am J Respir Crit Care Med 1994; 149: 60410. Number of ICS canisters per yearNumber of ICS canisters per year Rate ratio for death Rate ratio for death from asthmafrom asthma Canisters of SABA per monthCanisters o

5、f SABA per month Asthma deaths/10,000 Asthma deaths/10,000 patient-yearspatient-years 0 50 100 150 200 250 1234567 1 year risk of discontinuation: Age 4 4倍倍 SABASABA剂剂量量调调整整 症状症状恶恶化不同化不同阶阶段段(N = (N = 34153415) ) 症状最症状最严严重重时时 10-10-倍倍风险风险增增 加加 1010倍倍风险风险增加增加 在固定在固定剂剂量量ICS/LABAICS/LABA治治疗疗中，高中，高频频次的次的

6、SABASABA使用天数与急性使用天数与急性发发作相关作相关 0 0 5 5 1010 1515 2020 2525 3030 3535 4040 2 inh./day2 inh./day 4 inh./day4 inh./day 6 inh./day6 inh./day 8 inh./day8 inh./day % patients with asthma exacerbation in % patients with asthma exacerbation in the 3-week period after a high SABAthe 3-week period after a hig

7、h SABA dayday SAL/FLU 250/50 g bid (n = 1119)SAL/FLU 250/50 g bid (n = 1119) BUD/FORM 320/9 bid (n = 1099)BUD/FORM 320/9 bid (n = 1099) 增加？时间也许是调整治疗重要考量 在哮喘症状恶化时进行治疗与预防急性发作 研究显示临时将ICS剂量翻倍并不能带来降低急性发作的临床疗效 1,2 将ICS剂量提高至4倍，维持7-14天也许会有临床疗效，但缺乏循证 证据1 无论医生给患者医嘱是什么，患者在症状加重时通常会自行调节维持治 疗剂量3 平均来讲维持治疗的调整很有限并其调

8、整时间太晚 但SABA使用频次的早期及大幅度调整是风险增加的标志 ICS, inhaled corticosteroid; SABA, short-acting 2-agonist. 1. Quon BS et al. Cochrane Database Syst Rev 2010; 10: CD007524; 2. GINA. Global strategy for asthma management and prevention, 2012. Available at: /uploads/users/files/GINA_Report_2012

9、.pdf; 3. Partridge MR et al. BMC Pulm Med 2006; 6: 13. 早期干预 症状恶化早期伴随缓解药使用增加ICS吸入可以预防急性发作1,2 BUD/FORM, budesonide/formoterol; ICS, inhaled corticosteroid; LABA, long-acting 2-agonist; SABA, short-acting 2-agonist; SMART, budesonide/formoterol maintenance and reliever therapy Ankerst J et al. J Asthma

10、 2005; 42: 71524; 2. GINA. Global strategy for asthma management and prevention, 2012. Available at: /uploads/users/files/GINA_Report_2012.pdf 不同治不同治疗疗策略治策略治疗疗哮喘症状哮喘症状恶恶化的潜在不同化的潜在不同结结果果1 1 BUD/FORM BUD/FORM SMARTSMART 早期干早期干预预“ “机会窗机会窗” ” Changes in symptoms/reliever use may r

11、equire prompt treatment of exacerbations and early intervention with an as-needed reliever/controller* *Post-hoc analysis of 425 severe exacerbations diagnosed in the Formoterol and Corticosteroids Establishing Therapy study. PEF, peak expiratory flow. Tattersfield AE, et al. Am J Respir Crit Care M

12、ed 1999; 160: 5949. Optimal time to prevent Optimal time to prevent exacerbationsexacerbations COMPASSCOMPASS研究研究: SMART: SMART在机会窗中作用在机会窗中作用 Time to a high-reliever day (6 inhalations/day) is prolonged by BUD/FORM SMART Number of exacerbation days in the 3 weeks after a high-reliever day is reduced

13、 by BUD/FORM SMART BUD/FORM, budesonide/formoterol; SAL/FLU, salmeterol/fluticasone; SABA, short-acting 2-agonist; SMART, budesonide/formoterol maintenance and reliever therapy. Buhl R et al. Respir Res 2012; 13: 59. COMPASS: 更低的总总体体剂量 *Compared with higher-dose maintenance ICS/LABA plus SABA, in a

14、6-month, randomised, double-blind, double-dummy study (N = 3335); statistical analysis not performed. bid, twice daily; BDP, beclomethasone dipropionate; BUD/FORM, budesonide/formoterol; ICS, inhaled corticosteroid; LABA, long-acting 2- agonist; SABA, short-acting 2-agonist; SAL/FLU, salmeterol/flut

15、icasone; SMART, budesonide/formoterol maintenance and reliever therapy. 1. Kuna P, et al. Int J Clin Pract. 2007; 61(5): 72536. Mean daily ICS dose and adjusted equivalent BDP doseMean daily ICS dose and adjusted equivalent BDP dose* *1 1 SAL/FLU 250/50 g bid SAL/FLU 250/50 g bid plus plus SABASABA

16、BUD/FORM 320/9 g bid BUD/FORM 320/9 g bid plus SABAplus SABA BUD/FORM SMART BUD/FORM SMART 160/4.5 160/4.5 g bid + as g bid + as neededneeded 病毒感染是哮喘病毒感染是哮喘恶恶化和化和发发作的重要因素作的重要因素 患者自我报告的感冒次数与哮喘急性发作的关系 A retrospective analysis of five RCTs demonstrated an almost 10-fold increase in exacerbations during

17、 self-reported cold-periods on fixed-dose regimen plus SABA BUD/FORM, budesonide/formoterol; ICS, inhaled corticosteroid; LABA, long-acting 2-agonist; RCT, randomised controlled trial; SABA, short-acting 2-agonist; SMART, budesonide/formoterol maintenance and reliever therapy. Reddel HK, et al. Eur

18、Respir J 2011; 38: 58493 (figures adapted from original paper). Seasonality of cold periods on Seasonality of cold periods on fixed-dose fixed-dose maintenance ICS or ICS/LABA + SABA and on maintenance ICS or ICS/LABA + SABA and on BUD/FORM SMARTBUD/FORM SMART TreatmentTreatment Fixed-dose Fixed-dos

19、e maintenance ICS maintenance ICS or ICS/LABA + SABAor ICS/LABA + SABA Rate of colds per patient per yearRate of colds per patient per year Yearly exacerbation rateYearly exacerbation rate The time to first severe exacerbation from the onset of first reported cold was extended with BUD/FORM SMART SM

20、ILE 研究回顾分析: 季节性感冒与严重急性发作 Retrospective analysis of the SMILE study; *viral causation could not be confirmed; based on self-reported colds (pharyngitis and nasopharyngitis). BUD/FORM, budesonide/formoterol; HR, hazard ratio; SABA, short-acting 2-agonist; SMART, budesonide/formoterol maintenance and r

21、eliever therapy. Reddel HK, et al. Eur Respir J 2011; 38: 58493 (figures adapted from original paper). BUD/FORM SMART BUD/FORM + SABA 14% 4% SMART vs.ICS/LABA SMART vs.ICS/LABA SABA SABA 预预防冬季急性防冬季急性发发作作 Fewer winter exacerbations occurred in patients receiving BUD/FORM SMART vs. fixed-dose ICS/LABA

22、 plus SABA at a similar or higher maintenance dose BUD/FORM, budesonide/formoterol; ICS, inhaled corticosteroid; LABA, long-acting 2-agonist; SABA, short-acting 2-agonist; SMART, budesonide/formoterol maintenance and reliever therapy. Reddel H et al. Eur Respir J 2011; 38: 58493. 0.7 BUD/FORM BUD/FO

23、RM SMART SMART vsvs same fixed-dose ICS/LABA same fixed-dose ICS/LABA plus plus SABASABA BUD/FORM BUD/FORM SMART SMART vsvs higher fixed-dose higher fixed-dose ICS/LABA ICS/LABA plus SABAplus SABA Annualised exacerbation rate BUD/FORM BUD/FORM SMARTSMART Similar or higher fixed-dose Similar or highe

24、r fixed-dose ICS/LABA plus SABA ICS/LABA plus SABA 0 0.1 0.5 0.6 0.4 0.2 0.3 p 0.001 p 0.001 FACET研究：让你更好了解哮喘控制与急性发作的关系 The landmark FACET study had a factorial design and it remains one of very few studies that added a LABA (formoterol) to different ICS doses to assess how this strategy impacted ex

25、acerbations risk and daily asthma control bid, twice daily; BUD, budesonide; FACET, Formoterol And Corticosteroids Establishing Therapy; FORM, formoterol; ICS, inhaled corticosteroid; LABA, long-acting 2-agonist. Pauwels RA et al. N Engl J Med 1997; 337: 140511. Run-in BUD 100 BUD 100 g g plus place

26、bo bidplus placebo bid (n = 213)(n = 213) BUD 100 g BUD 100 g + FORM 12 + FORM 12 g g bid bid ( (n = 210)n = 210) Visit 1Visit 1 2 3 4 5 2 3 4 5 6 6 7 8 7 8 9 9 Month: Month: 1 1 0 0 0.50.51 2 3 6 1 2 3 6 9 12 9 12 Budesonide Budesonide 800 800 g bidg bid Enrolled: N = 1114 Randomised: n = 852 Rando

27、misationRandomisation 哮喘当前控制与急性发作预防完全相关吗？ In FACET, a 4-fold higher dose of ICS led to a greater reduction in future risk (exacerbations) than addition of formoterol to low-dose ICS, BUT the opposite was true for clinical control (episode-free days) BUD, budesonide; FACET, Formoterol And Corticoster

28、oids Establishing Therapy; FORM, formoterol; ICS, inhaled corticosteroid; PEF, peak expiratory flow. Pauwels RA et al. N Engl J Med 1997; 337: 140511. 0 50 75 25 42 46 51 55 Mean episode-free days (No symptoms or rescue use and normal PEF values) % FORM vs FORM vs placebo placebo p = 0.001p = 0.001

29、Lower- Lower- vs vs higher-dose BUDhigher-dose BUD p = 0.16p = 0.16 BUD 200 g BUD 800 g + FORM 24 g BUD 800 g BUD 200 g + FORM 24 g BUD 200 g BUD 800 g + FORM 24 g 0 60 90 30 91 BUD 800 g BUD 200 g + FORM 24 g 46 67 34 Severe exacerbations No. per 100 patients/year FORM vs FORM vs placebo placebo p

30、= 0.01p = 0.01 Lower- Lower- vs vs higher-dose BUDhigher-dose BUD p 0.001 p 0.001 关于哮喘全面控制（OAC）- FACET / GOAL 研究的启示 The GINA guidelines state that control of asthma involves both current control and longer-term components, referred to as future risk1 FACET, Formoterol And Corticosteroids Establishin

31、g Therapy; GINA, Global initiative for asthma; GOAL, Gaining Optimal Asthma controL; ICS, inhaled corticosteroid; LABA, long-acting 2-agonist. 1. GINA, Global strategy for asthma management and prevention, 2012. Available at: /uploads/users/files/GINA_Report_2012.pdf; 2. Batem

32、an ED et al. J Allergy Clin Immunol 2010; 125: 6008. 2 In patients not controlled on ICSIn patients not controlled on ICS 2 SMART RCT临床研究汇总 (N = 14,385) bid, twice daily; BUD/FORM, budesonide/formoterol; od, once daily; SABA, short-acting 2-agonist; SAL/FLU, salmeterol /fluticasone; SMART, budesonid

33、e/formoterol maintenance and reliever therapy. 1. Rabe KF et al. Chest 2006; 129: 24556; 2. Scicchitano R et al. Curr Med Res Opin 2004; 20: 140318; 3. OByrne PM et al. Am J Respir Crit Care Med 2005; 171: 12936; 4. Rabe KF et al. Lancet 2006; 368: 74453; 5. Kuna P et al. Int J Clin Pract 2007; 61:

34、72536; 6. Bousquet J et al. Respir Med 2007; 101: 243746. STEPSTEP2 2 n = 1890 n = 1890 12 months duration12 months duration BUD/FORM SMART 2 x 160/4.5 g od + as needed BUD 2 x 160 g bid + SABA STAYSTAY3 3 n = 2760n = 2760 12 months duration12 months duration BUD/FORM SMART 80/4.5 g bid + as needed

35、BUD 320 g bid + SABA BUD/FORM 80/4.5 g bid + SABA COMPASSCOMPASS5 5 n = 3335n = 3335 6 months duration6 months duration BUD/FORM SMART 160/4.5 g bid + as needed BUD/FORM 320/9 g bid + SABA SAL/FLU 50/250 g bid + SABA SMILESMILE4 4 n = 3394n = 3394 12 months duration12 months duration BUD/FORM SMART

36、160/4.5 g bid + as needed BUD/FORM 160/4.5 g bid + SABA AHEADAHEAD6 6 n = 2309n = 2309 6 months duration6 months duration BUD/FORM SMART 2 x 160/4.5 g bid + as needed SAL/FLU 50/500 g bid + SABA STEAMSTEAM1 1 n = 697n = 697 6 months duration6 months duration BUD/FORM SMART 2 x 80/4.5 g od + as neede

37、d BUD 2 x 160 g od + SABA Once-daily Once-daily SMART studiesSMART studies SMART RCT临床研究汇总 (N = 14,385) BUD, budesonide; FACET, Formoterol And Corticosteroids Establishing Therapy; FORM, formoterol; GOAL, Gaining Optimal Asthma controL; mod., moderate; SABA, short-acting 2-agonist; SAL/FLU, salmeter

38、ol/fluticasone; SMART, budesonide/formoterol maintenance and reliever therapy. 1. Rabe KF et al. Chest 2006; 129: 24556; 2. Scicchitano R et al. Curr Med Res Opin 2004; 20: 140318; 3. OByrne PM et al. Am J Respir Crit Care Med 2005; 171: 12936; 4. Rabe KF et al. Lancet 2006; 368: 74453; 5. Kuna P et

39、 al. Int J Clin Pract 2007; 61: 72536; 6. Bousquet J et al. Respir Med 2007; 101: 243746. STEPSTEP2 2 n = 1890 n = 1890 12 months duration12 months duration SMART 2 x 160/4.5 g od + as needed BUD 2 x 160 g bid + SABA STAYSTAY3 3 n = 2760n = 2760 12 months duration12 months duration SMART 80/4.5 g bi

40、d + as needed BUD 320 g bid + SABA BUD/FORM 80/4.5 g bid + SABA COMPASSCOMPASS5 5 n = 3335n = 3335 6 months duration6 months duration SMART 160/4.5 g bid + as needed BUD/FORM 320/9 g bid + SABA FLU/SAL 250/50 g bid + SABA SMILESMILE4 4 n = 3394n = 3394 12 months duration12 months duration SMART 160/

41、4.5 g bid + as needed BUD/FORM 160/4.5 g bid + SABA AHEADAHEAD6 6 n = 2309n = 2309 6 months duration6 months duration SMART 2 x 160/4.5 g bid + as needed FLU/SAL 500/50 g bid + SABA STEAMSTEAM1 1 n = 697n = 697 6 months duration6 months duration SMART 2 x 80/4.5 g od + as needed BUD 2 x 160 g bid +

42、SABA Once-daily Once-daily SMART studiesSMART studies Is Is once-daily once-daily SMART SMART effective in mild/mod. effective in mild/mod. asthma?asthma? Is Is once-daily once-daily SMART SMART effective in mod./severe effective in mod./severe asthma?asthma? Will SMART facilitate low-Will SMART fac

43、ilitate low- dose maintenance without dose maintenance without increased future risk increased future risk (beyond FACET)?(beyond FACET)? Do both Do both FORM and BUD as FORM and BUD as needed contribute to better needed contribute to better control with SMART?control with SMART? Will SMART beat the

44、 overall Will SMART beat the overall asthma control seen on asthma control seen on high-dose FACET therapy?high-dose FACET therapy? Will SMART beat the control Will SMART beat the control seen with max. SAL/FLU as seen with max. SAL/FLU as in GOAL?in GOAL? 哮喘循证医学证据的日益积累 推动哮喘指南更新和治疗理念进步 2004年 STEP GO

45、AL 2006年 SMILE STEA M 治 疗 理 念 2002年 基于专家意见 基于循证医学证据 轻度哮喘也需 控制药物治疗， 首选ICS 2006年 基于严重程度 基于哮喘控制 ICS/LABA 单一吸入装置 治疗 2010年 哮喘临床控制 + 降低未来风险 2014年1 ICS/LABA为3级及以上治疗首选控制 药物（12岁以上儿童及成人）； SMART疗法较固定剂量ICS/LABA或 更高剂量ICS，在过去1年AE1次的患 者中更优 ICS+LABA 联合治疗优于 高剂量ICS ICS/LABA 维持+缓解治疗 （SMART疗法） 2014年 哮喘症状控制 + 降低未来风险 199

46、7年 FACET 2001年 OPTIMAL 2003年 START 2005年 STAY COSMOS 2007年 COMPASS AHEAD 2011年 Bateman 事后分析 2010年 EUROSMART Bateman回顾分析 2013年 SMARTASIA 循 证 依 据 1993年 GINA正式成立 1995年 首部GINA诞生 2002年 GINA科学委员会成立2006年 GINA更新 2010年 GINA更新 2014年 GINA更新 指 南 更 新 2015年 GINA更新 布地奈德/福莫特罗SMART研究汇总 研究名称对照组日常临床 控制 减少急性发作 STEAM3 S

47、TEP2 vs 2xICS+SABA 更优更优 STAY1vs 4xICS+SABA 更优更优 COSMOS5 SMILE4 vs ICS/LABA+SABA 更优 或相当 更优 COMPASS6, AHEAD7vs 2xICS/LABA+SABA 相当更优 1. OByrne PM, et al. Am J Respir Crit Care Med 2005；2.Scicchitano R, et al. Curr Med Res Opin 2004；3. Rabe KF, et al. Chest 2006；4. Rabe KF, et al. Lancet 2006；5. Vogelme

48、ier C, et al. Eur Respir J 2005 ；6. Kuna P, et al. Int J Clin Pract 2007；7. Bousquet J, et al. Respiratory Medicine 2007； GINA 2006： 正式认可SMART疗法在哮喘治疗中的地位 STEAM1 STAY2 STEP3 COSMOS4 GINA 2006 l使用含有福莫特罗和布地奈德的联 合吸入制剂，既可用于急救也可用 于维持治疗。 l布地奈德-福莫特罗两种成分同时 按需给药，可增加对患者发生重度 急性发作的预防保护作用，并可在 相对低剂量情况下改善哮喘控制。 1. R

49、abe KF, et al. Chest 2006;129:246-256 2. OByrne PM, et al. Am J Respir Crit Care Med Vol 171. pp 129136, 2005 3. Scicchitano R, et al. CURRENT MEDICAL RESEARCH AND OPINION VOL. 20, NO. 9, 2004, 14031418 4. Vogelmeier C, et al. Eur Respir J 2005; 26: 819828 5. GINA report 2006. SMILE（2006）：SMART疗法在减少

50、急性加重、 改善肺功能方面优于布地奈德/福莫特罗维持加 按需使用福莫特罗或特布他林 布地奈德/福莫特罗维持缓解治疗降低瞬时风险 27% vs 布地奈德/福莫特罗+ 福莫特罗 45% vs 布地奈德/福莫特罗+ SABA 特布他林 福莫特罗 布地奈德/福莫特罗 布地奈德/福莫 特罗维持治疗+ 按需使用: 与布地奈德/福莫特罗维持治疗加按需使用福莫特罗或特布他林治疗比较，维持 加按需使用布地奈德/福莫特罗能减少严重发作的危险性，且能显著增加FEV1 Rabe KF, et al. Lancet 2006; 368: 74453 COMPASS研究（2007）：SMART疗法与更高剂 量的固定维持疗

51、法相比，改善哮喘控制同样有效 l与更高剂量固定维持疗法相比，SMART疗法在减少ICS总体剂量25% （BDP 等效剂量）的情况下，仍改善哮喘控制，且减少急性发作更有效。 l因此，SMART疗法可以达到与固定剂量联合治疗同样的哮喘控制水平，并进 一步减少急性发作和药物负荷。 Kuna P, et al. Int J Clin Pract, May 2007, 61, 5, 725736 AHEAD研究（2007，2012）： 充分证实SMART疗法对急性发作高风险患者的疗效 为期6个月的随机、双盲、平行分组、多中心研究，包括中国在内的17个国家、184个中心共2309例哮喘 患者入组。入选患者

52、为既往1年有1次及以上急性发作史的患者。主要研究终点：到首次严重哮喘急性发作 时间；次要终点包括肺功能、症状控制及生活质量的评估。 Bousquet J, et al. Respiratory Medicine (2007) 101, 24372446 Lin JT, et al. Chin Med J 2012;125(17):2994-3001 在减少ICS总体剂量的情况下，BUD/FM维持和缓解治疗与高剂量SAL/FP+SABA相比，可显著 减少重度急性发作率和急诊/住院率，相比总体研究人群，BUD/FM在中国亚组人群中更有效。 25 9 31 13 0 20 40 重度急性发作急诊或住

53、院 发生次数/100例患者/年 BUD/FM维持和缓解治疗高剂量SAL/FP维持+SABA P=0.039 P=0.046 总体研究人群（n=2309） 中国亚组分析人群（n=222） 布地奈德/福莫特罗，n=111 沙美特罗/氟替卡松，n=111 55% 重度急性发作平均次数/患者 n=1154n=1155 急性发作风险荟萃分析: 固定剂量ICS/LABA 及 SMART vs. 更高固定剂量ICS BUD/FORM: budesonide/formoterol; ICS, inhaled corticosteroid; LABA, long-acting 2-agonist; SMART,

54、 budesonide/formoterol maintenance and reliever therapy. BUD/FORM, budesonide/formoterol; CI, confidence interval; ICS, inhaled corticosteroids; LABA, long-acting 2-agonist; SMART, budesonide/formoterol maintenance and reliever therapy. Edwards SJ et al. Int J Clin Pract 2010; 64: 61927. FAVOURS ICS

55、/LABA FAVOURS HIGHER-DOSE ICS Sin et al. JAMA 2004 ICS + LABA vs higher-dose ICS (N = 5680) 0.551.0 Risk of severe exacerbation (95% CI) 0.86 (0.76, 0.97) 14% reduction 0.1 BUD/FORM SMART studies versus higher dose ICS Gibson et al. JACI 2007 ICS + LABA vs higher-dose ICS (N = 4140) 0.88 (0.76, 1.01

56、) 12% reduction (not significant) Fixed ICS/LABA versus higher-dose ICS Rabe et al. Chest 2006 STEAM (BUD/FORM SMART vs 2 x ICS) N = 696 Scicchitano et al. CMRO 2004 STEP (BUD/FORM SMART vs 2 x ICS) N = 1890) OByrne et al. AJRCCM 2005 STAY (SMART vs 4 x ICS) N=1846 0.61 (0.50, 0.74) 39% reduction 0.

57、46 (0.29, 0.73) 54% reduction 0.55 (0.44, 0.67) 45% reduction BUD/FORM SMART meta-anaysis 0.59 (0.51, 0.68) 41% reduction Edwards et al. Int J Clin Pract 2010 BUD/FORM SMART vs 24 higher-dose ICS (N = 4433) Once daily Safety data from 6 double-blind RCTs in which BUD/FORM SMART was used for 6 months

58、 in patients with asthma were reviewed There were no notable differences between BUD/FORM SMART and alternative fixed dose- treatment in terms of the incidence of 2-agonist or ICS class-related AEs SMART 安全性荟萃分析 - LABA或ICS使用相关不良事件 *Pneumonia was included for completeness, due to the current debate o

59、n the relationship between ICS use and pneumonia risk in COPD; as there were multiple arms in some of the clinical trials, the number of patients in the comparator groups exceed those in the BUD/FORM SMART groups. AEs, adverse events; BUD/FORM, budesonide/formoterol; ICS, inhaled corticosteroid; SMA

60、RT, budesonide/formoterol maintenance and reliever therapy. Sears MR et al. Respir Med 2009; 103: 19608. SMART SMART 安全性安全性荟荟萃分析萃分析 - -哮喘相关事件哮喘相关事件 Asthma-related DAEs and SAEs were significantly reduced with BUD/FORM SMART vs comparator therapy DAEs: 0.45% vs 0.97% (ARR = 0.52%); pooled MH RR 0.43,