提示: 手机请竖屏浏览!

布地奈德-福莫特罗按需用药治疗轻度哮喘的对照试验
Controlled Trial of Budesonide–Formoterol as Needed for Mild Asthma


Richard Beasley ... 呼吸系统疾病 • 2019.05.23
相关阅读
• 轻度哮喘可否仅采用吸入型类固醇联合支气管扩张药按需用药 • 布地奈德-福莫特罗按需用药可否治疗间歇性轻度哮喘 • 莫米松或噻托溴胺治疗痰嗜酸性粒细胞低水平的轻度哮喘 • 我们应如何治疗轻度哮喘患者 • 布地奈德-福莫特罗按需用药与布地奈德维持用药治疗轻度哮喘的比较

摘要


背景

在双盲、安慰剂对照试验中,与短效β2受体激动剂(SABA)按需用药相比,布地奈德-福莫特罗按需用药降低了哮喘重度发作风险;风险与布地奈德维持治疗+SABA按需用药相似。如果我们可以从旨在更好地反映临床实践的临床试验中获得数据,将会非常有益。

 

方法

我们在轻度哮喘成人患者中开展了一项为期52周的随机、开放标签、平行组、对照试验。患者被随机分配到三个治疗组之一:沙丁胺醇(根据哮喘症状按需从加压定量吸入器吸入2揿,每揿100 μg)(沙丁胺醇组);布地奈德(每日2次,每次通过都保吸入器吸入1吸,每吸200 μg)+沙丁胺醇按需用药(布地奈德维持治疗组);或者布地奈德-福莫特罗(按需通过都保吸入器吸入1吸,每吸200 μg布地奈德和6 μg福莫特罗)(布地奈德-福莫特罗组)。研究中利用吸入器的电子监测装置测定用药情况。主要结局是哮喘的年发作率。

 

结果

分析包括被随机分组的675例患者中的668例。布地奈德-福莫特罗组的哮喘年发作率比沙丁胺醇组低(绝对率,0.195 vs. 0.400;相对率,0.49;95%置信区间[CI],0.33~0.72;P<0.001),与布地奈德维持治疗组无显著差异(绝对率,布地奈德-福莫特罗组0.195 vs.布地奈德维持治疗组0.175;相对率,1.12;95% CI,0.70~1.79;P=0.65)。布地奈德-福莫特罗组的重度发作次数比沙丁胺醇组(9 vs. 23;相对危险度,0.40;95% CI,0.18~0.86)和布地奈德维持治疗组(9 vs. 21;相对危险度,0.44;95% CI,0.20~0.96)少。在布地奈德-福莫特罗组和布地奈德维持治疗组中,患者吸入布地奈德的平均(±SD)剂量分别为每日107 μg±109 μg和每日222 μg±113 μg。本试验报道的不良事件发生率和类型与之前试验报道的一致,与临床应用中报道的也一致。

 

结论

在对轻度哮喘成人患者进行的开放标签试验中,在预防哮喘发作方面,布地奈德-福莫特罗按需用药优于沙丁胺醇按需用药(由阿斯利康和新西兰健康研究理事会[Health Research Council of New Zealand]资助;Novel START在Australian New Zealand Clinical Trials注册号为ACTRN12609000593235)。





作者信息

Richard Beasley, D.Sc., Mark Holliday, B.Sc., Helen K. Reddel, Ph.D., Irene Braithwaite, Ph.D., Stefan Ebmeier, B.M., B.Ch., Robert J. Hancox, M.D., Tim Harrison, M.D., Claire Houghton, B.M., B.S., Karen Oldfield, M.B., Ch.B., Alberto Papi, M.D., Ian D. Pavord, F.Med.Sci., Mathew Williams, Dip.Ex.Sci., and Mark Weatherall, F.R.A.C.P. for the Novel START Study Team*
From the Medical Research Institute of New Zealand (R.B., M.H., I.B., S.E., C.H., K.O., M. Williams), the Capital and Coast District Health Board (R.B.), and the University of Otago Wellington (M. Weatherall), Wellington, the Department of Respiratory Medicine, Waikato Hospital, Hamilton (R.J.H.), and the Department of Preventive and Social Medicine, University of Otago, Dunedin (R.J.H.) — all in New Zealand; Woolcock Institute of Medical Research, University of Sydney, Sydney (H.K.R.); the Nottingham NIHR Biomedical Research Centre, University of Nottingham, Nottingham (T.H.), and the Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford (I.D.P.) — both in the United Kingdom; and the Respiratory Medicine Unit, Department of Medical Sciences, Università di Ferrara, Ferrara, Italy (A.P.). Address reprint requests to Dr. Beasley at the Medical Research Institute of New Zealand, Private Bag 7902, Newtown, Wellington 6242, New Zealand, or at richard.beasley@mrinz.ac.nz. *A complete list of investigators in the Novel START trial is provided in the Supplementary Appendix, available at NEJM.org.

 

参考文献

1. Dusser D, Montani D, Chanez P, et al. Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations. Allergy 2007;62:591-604.

2. Reddel HK, Busse WW, Pedersen S, et al. Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency: a post-hoc efficacy analysis of the START study. Lancet 2017;389:157-166.

3. Cochrane MG, Bala MV, Downs KE, Mauskopf J, Ben-Joseph RH. Inhaled corticosteroids for asthma therapy: patient compliance, devices, and inhalation technique. Chest 2000;117:542-550.

4. Beasley R, Weatherall M, Shirtcliffe P, Hancox R, Reddel HK. Combination corticosteroid/β-agonist inhaler as reliever therapy: a solution for intermittent and mild asthma? J Allergy Clin Immunol 2014;133:39-41.

5. O’Byrne PM, Jenkins C, Bateman ED. The paradoxes of asthma management: time for a new approach? Eur Respir J 2017;50(3):1701103.

6. Beasley R, Bird G, Harper J, Weatherall M. The further paradoxes of asthma management: time for a new approach across the spectrum of asthma severity. Eur Respir J 2018;52(5):1800694.

7. O’Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N Engl J Med 2018;378:1865-1876.

8. Bateman ED, Reddel HK, O’Byrne PM, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N Engl J Med 2018;378:1877-1887.

9. Global Initiative for Asthma (GINA) home page. 2018 (http://www.ginasthma.org/).

10. British Thoracic Society, Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. SIGN 153. September 2016 (https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma/).

11. Beasley R, Pavord I, Papi A, et al. Description of a randomised controlled trial of inhaled corticosteroid/fast-onset LABA reliever therapy in mild asthma. Eur Respir J 2016;47:981-984.

12. Pilcher J, Holliday M, Ebmeier S, et al. Validation of a metered dose inhaler electronic monitoring device: implications for asthma clinical trial use. BMJ Open Respir Res 2016;3(1):e000128-e000128.

13. Pilcher J, Shirtcliffe P, Patel M, et al. Three-month validation of a turbuhaler electronic monitoring device: implications for asthma clinical trial use. BMJ Open Respir Res 2015;2(1):e000097-e000097.

14. Patel M, Pilcher J, Pritchard A, et al. Efficacy and safety of maintenance and reliever combination budesonide-formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial. Lancet Respir Med 2013;1:32-42.

15. Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med 2009;180:59-99.

16. Juniper EF, Svensson K, Mörk A-C, Ståhl E. Measurement properties and interpretation of three shortened versions of the Asthma Control Questionnaire. Respir Med 2005;99:553-558.

17. Sobieraj DM, Weeda ER, Nguyen E, et al. Association of inhaled corticosteroids and long-acting beta-agonists as controller and quick relief therapy with exacerbations and symptom control in persistent asthma: a systematic review and meta-analysis. JAMA 2018;319:1485-1496.

18. Edmonds ML, Milan SJ, Camargo CA Jr, Pollack CV, Rowe BH. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst Rev 2012;12:CD002308-CD002308.

19. Rodrigo GJ. Rapid effects of inhaled corticosteroids in acute asthma: an evidence-based evaluation. Chest 2006;130:1301-1311.

20. McKeever T, Mortimer K, Wilson A, et al. Quadrupling the inhaled glucocorticoid dose to abort asthma exacerbations. N Engl J Med 2018;378:902-910.

21. Papi A, Canonica GW, Maestrelli P, et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N Engl J Med 2007;356:2040-2052.

22. Beasley R, Hancox RJ, Harwood M, et al. Asthma and respiratory foundation NZ adult asthma guidelines: a quick reference guide. N Z Med J 2016;129:83-102.

23. Balanag VM, Yunus F, Yang PC, Jorup C. Efficacy and safety of budesonide/formoterol compared with salbutamol in the treatment of acute asthma. Pulm Pharmacol Ther 2006;19:139-147.

24. Rubinfeld AR, Scicchitano R, Hunt A, Thompson PJ, Van Nooten A, Selroos O. Formoterol Turbuhaler as reliever medication in patients with acute asthma. Eur Respir J 2006;27:735-741.

服务条款 | 隐私政策 | 联系我们