醫(yī)學(xué)交流課件：治療策略對哮喘控制的影響

1、治療策略對哮喘控制的影響 僅供醫(yī)療專業(yè)人士進行醫(yī)學(xué)科學(xué)交流，不可用于推廣目的 大綱 哮喘控制不佳的原因 哮喘是一個炎癥和癥狀波動的疾病 維持緩解治療 哮喘全面控制哮喘全面控制: : 當(dāng)前當(dāng)前控制和未來控制和未來風(fēng)險風(fēng)險 GINA 指南指出哮喘控制包括當(dāng)前控制和未來風(fēng)險兩個方面 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：真實實世界哮喘患者世界哮喘患者ICSICS使用不足和使用不足和過過度使用度使用 AIRE研究顯示： 使用ICS+SABA或ICS/LABA+ SABA治療的哮喘患者入組研究前一 個月內(nèi)緩解藥（SABA）使用頻次超過抗炎藥物（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 (%)(%) 過過度度SABASABA吸入及吸入及ICSICS使用不足使用不足導(dǎo)導(dǎo)致哮喘相關(guān)死亡率升高致哮喘相關(guān)死亡率升高 在控制藥物使用不足的情況下過分依賴緩解藥（SABA）與哮喘相關(guān)死亡率相關(guān) 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劑劑量量調(diào)調(diào)整整 癥狀癥狀惡惡化不同化不同階階段段(N = (N = 34153415) ) 癥狀最癥狀最嚴(yán)嚴(yán)重重時時 10-10-倍倍風(fēng)險風(fēng)險增增 加加 1010倍倍風(fēng)險風(fēng)險增加增加 在固定在固定劑劑量量ICS/LABAICS/LABA治治療療中，高中，高頻頻次的次的

6、SABASABA使用天數(shù)與急性使用天數(shù)與急性發(fā)發(fā)作相關(guān)作相關(guān) 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？時間也許是調(diào)整治療重要考量 在哮喘癥狀惡化時進行治療與預(yù)防急性發(fā)作 研究顯示臨時將ICS劑量翻倍并不能帶來降低急性發(fā)作的臨床療效 1,2 將ICS劑量提高至4倍，維持7-14天也許會有臨床療效，但缺乏循證 證據(jù)1 無論醫(yī)生給患者醫(yī)囑是什么，患者在癥狀加重時通常會自行調(diào)節(jié)維持治 療劑量3 平均來講維持治療的調(diào)整很有限并其調(diào)

8、整時間太晚 但SABA使用頻次的早期及大幅度調(diào)整是風(fēng)險增加的標(biāo)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. 早期干預(yù) 癥狀惡化早期伴隨緩解藥使用增加ICS吸入可以預(yù)防急性發(fā)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 不同治不同治療療策略治策略治療療哮喘癥狀哮喘癥狀惡惡化的潛在不同化的潛在不同結(jié)結(jié)果果1 1 BUD/FORM BUD/FORM SMARTSMART 早期干早期干預(yù)預(yù)“ “機會窗機會窗” ” 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在機會窗中作用在機會窗中作用 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: 更低的總總體體劑量 *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惡惡化和化和發(fā)發(fā)作的重要因素作的重要因素 患者自我報告的感冒次數(shù)與哮喘急性發(fā)作的關(guān)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 研究回顧分析: 季節(jié)性感冒與嚴(yán)重急性發(fā)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 預(yù)預(yù)防冬季急性防冬季急性發(fā)發(fā)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：讓你更好了解哮喘控制與急性發(fā)作的關(guān)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 哮喘當(dāng)前控制與急性發(fā)作預(yù)防完全相關(guān)嗎？ 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 關(guān)于哮喘全面控制（OAC）- FACET / GOAL 研究的啟示 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臨床研究匯總 (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臨床研究匯總 (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? 哮喘循證醫(yī)學(xué)證據(jù)的日益積累 推動哮喘指南更新和治療理念進步 2004年 STEP GO

45、AL 2006年 SMILE STEA M 治 療 理 念 2002年 基于專家意見 基于循證醫(yī)學(xué)證據(jù) 輕度哮喘也需 控制藥物治療， 首選ICS 2006年 基于嚴(yán)重程度 基于哮喘控制 ICS/LABA 單一吸入裝置 治療 2010年 哮喘臨床控制 + 降低未來風(fēng)險 2014年1 ICS/LABA為3級及以上治療首選控制 藥物（12歲以上兒童及成人）； SMART療法較固定劑量ICS/LABA或 更高劑量ICS，在過去1年AE1次的患 者中更優(yōu) ICS+LABA 聯(lián)合治療優(yōu)于 高劑量ICS ICS/LABA 維持+緩解治療 （SMART療法） 2014年 哮喘癥狀控制 + 降低未來風(fēng)險 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回顧分析 2013年 SMARTASIA 循 證 依 據(jù) 1993年 GINA正式成立 1995年 首部GINA誕生 2002年 GINA科學(xué)委員會成立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/福莫特羅SMART研究匯總 研究名稱對照組日常臨床 控制 減少急性發(fā)作 STEAM3 S

47、TEP2 vs 2xICS+SABA 更優(yōu)更優(yōu) STAY1vs 4xICS+SABA 更優(yōu)更優(yōu) COSMOS5 SMILE4 vs ICS/LABA+SABA 更優(yōu) 或相當(dāng) 更優(yōu) COMPASS6, AHEAD7vs 2xICS/LABA+SABA 相當(dāng)更優(yōu) 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： 正式認可SMART療法在哮喘治療中的地位 STEAM1 STAY2 STEP3 COSMOS4 GINA 2006 l使用含有福莫特羅和布地奈德的聯(lián) 合吸入制劑，既可用于急救也可用 于維持治療。 l布地奈德-福莫特羅兩種成分同時 按需給藥，可增加對患者發(fā)生重度 急性發(fā)作的預(yù)防保護作用，并可在 相對低劑量情況下改善哮喘控制。 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療法在減少

50、急性加重、 改善肺功能方面優(yōu)于布地奈德/福莫特羅維持加 按需使用福莫特羅或特布他林 布地奈德/福莫特羅維持緩解治療降低瞬時風(fēng)險 27% vs 布地奈德/福莫特羅+ 福莫特羅 45% vs 布地奈德/福莫特羅+ SABA 特布他林 福莫特羅 布地奈德/福莫特羅 布地奈德/福莫 特羅維持治療+ 按需使用: 與布地奈德/福莫特羅維持治療加按需使用福莫特羅或特布他林治療比較，維持 加按需使用布地奈德/福莫特羅能減少嚴(yán)重發(fā)作的危險性，且能顯著增加FEV1 Rabe KF, et al. Lancet 2006; 368: 74453 COMPASS研究（2007）：SMART療法與更高劑 量的固定維持療

51、法相比，改善哮喘控制同樣有效 l與更高劑量固定維持療法相比，SMART療法在減少ICS總體劑量25% （BDP 等效劑量）的情況下，仍改善哮喘控制，且減少急性發(fā)作更有效。 l因此，SMART療法可以達到與固定劑量聯(lián)合治療同樣的哮喘控制水平，并進 一步減少急性發(fā)作和藥物負荷。 Kuna P, et al. Int J Clin Pract, May 2007, 61, 5, 725736 AHEAD研究（2007，2012）： 充分證實SMART療法對急性發(fā)作高風(fēng)險患者的療效 為期6個月的隨機、雙盲、平行分組、多中心研究，包括中國在內(nèi)的17個國家、184個中心共2309例哮喘 患者入組。入選患者

52、為既往1年有1次及以上急性發(fā)作史的患者。主要研究終點：到首次嚴(yán)重哮喘急性發(fā)作 時間；次要終點包括肺功能、癥狀控制及生活質(zhì)量的評估。 Bousquet J, et al. Respiratory Medicine (2007) 101, 24372446 Lin JT, et al. Chin Med J 2012;125(17):2994-3001 在減少ICS總體劑量的情況下，BUD/FM維持和緩解治療與高劑量SAL/FP+SABA相比，可顯著 減少重度急性發(fā)作率和急診/住院率，相比總體研究人群，BUD/FM在中國亞組人群中更有效。 25 9 31 13 0 20 40 重度急性發(fā)作急診或住

53、院 發(fā)生次數(shù)/100例患者/年 BUD/FM維持和緩解治療高劑量SAL/FP維持+SABA P=0.039 P=0.046 總體研究人群（n=2309） 中國亞組分析人群（n=222） 布地奈德/福莫特羅，n=111 沙美特羅/氟替卡松，n=111 55% 重度急性發(fā)作平均次數(shù)/患者 n=1154n=1155 急性發(fā)作風(fēng)險薈萃分析: 固定劑量ICS/LABA 及 SMART vs. 更高固定劑量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 安全性薈萃分析 - LABA或ICS使用相關(guān)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 安全性安全性薈薈萃分析萃分析 - -哮喘相關(guān)事件哮喘相關(guān)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,