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Combination inhaled steroid and long-acting beta2-agonist versus tiotropium for chronic obstructive pulmonary disease

  1. Emma J Welsh1,*,
  2. Christopher J Cates1,
  3. Phillippa Poole2

Editorial Group: Cochrane Airways Group

Published Online: 31 MAY 2013

Assessed as up-to-date: 30 NOV 2012

DOI: 10.1002/14651858.CD007891.pub3


How to Cite

Welsh EJ, Cates CJ, Poole P. Combination inhaled steroid and long-acting beta2-agonist versus tiotropium for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD007891. DOI: 10.1002/14651858.CD007891.pub3.

Author Information

  1. 1

    St George's University of London, Population Health Sciences and Education, London, UK

  2. 2

    University of Auckland, Department of Medicine, Auckland, New Zealand

*Emma J Welsh, Population Health Sciences and Education, St George's University of London, Cranmer Terrace, London, SW17 0RE, UK. ewelsh@sgul.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 31 MAY 2013

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Fang 2008 {published data only}
  • Fang LZ, Liang X, Zhang JQ, Liu L, Fu WP, Zhao ZH, et al. Combination of inhaled salmeterol/fluticasone and tiotropium in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Chung-Hua Chieh Ho Ho Hu Hsi Tsa Chih [Chinese Journal of Tuberculosis & Respiratory Diseases] 2008;31(11):811-4. [: 1001-0939]
INSPIRE {published data only}
  • Calverley P, Stockley R, Seemungal T, Hagan G, Wedzicha J. Adverse events and mortality in the INSPIRE study (investigating new standards for prophylaxis in reduction of exacerbations) [Abstract]. European Respiratory Journal 2007;30(Suppl 51):125s [P847].
  • Calverley PM, Stockley RA, Seemungal TA, Hagan G, Willits LR, Riley JH, et al. Reported pneumonia in patients with COPD: Findings from the INSPIRE study. Chest 2011;139(3):505-12.
  • GSK (SCO40036). Multicentre, randomised, double-blind, double dummy, parallel group, 104-week study to compare the effect of the salmeterol/fluticasone propionate combination product (SERETIDE*) 50/500mcg delivered twice daily via the DISKUS*/ACCUHALER* inhaler with tiotropium bromide 18 mcg delivered once daily via the Handihaler inhalation device on the rate of health care utilisation exacerbations in subjects with severe chronic obstructive pulmonary disease (COPD). www.gsk-clinicalstudyregister.com/files/pdf/21085.pdf (accessed 16 June 2009).
  • Seemungal T, Stockley R, Calverley P, Hagan G, Wedzicha J. Effect of fluticasone/salmeterol propionate versus tiotropium bromide on exacerbations: the INSPIRE study (investigating new standards for prophylaxis in reduction of exacerbations) [Abstract]. European Respiratory Journal 2007;30(Suppl 51):688s [E4055].
  • Seemungal T, Stockley R, Calverley P, Hagan G, Wedzicha JA. Investigating new standards for prophylaxis in reduction of exacerbations - The INSPIRE study methodology. COPD: Journal of Chronic Obstructive Pulmonary Disease 2007;4(3):177-83.
  • Stockley R, Calverley P, Seemungal T, Hagan G, Wedzicha J. Effect of fluticasone/salmeterol propionate versus tiotropium bromide on withdrawal rate, health status, lung function and mortality INSPIRE (investigating new standards for prophylaxis in reduction of exacerbations study) [Abstract]. European Respiratory Journal 2007;30(Suppl 51):34s [388].
  • Wedzicha J, Stockley R, Seemungal T, Hagan G, Calverley P. The INSPIRE study: effect of fluticasone/salmeterol propionate versus tiotropium bromide on COPD exacerbations [Abstract]. Respirology 2007;12(Suppl 4):A112.
  • Wedzicha JA, Calverley PM, Seemungal TA, Hagan G, Ansari Z, Stockley RA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by fluticasone/salmeterol propionate or tiotropium bromide. American Journal of Respiratory & Critical Care Medicine 2008;177(1):19-26.
SCO40034 {unpublished data only}
  • GSK (SCO40034). A multicentre, randomised, double-blind, double dummy, parallel group 12-week exploratory study to compare the effect of the fluticasone/salmeterol propionate combination product (SERETIDE™) 50/500mcg bd via the DISKUS™/ACCUHALER™ inhaler with tiotropium bromide 18 mcg od via the Handihaler inhalation device on efficacy and safety in patients with chronic obstructive pulmonary disease (COPD). www.gsk-clinicalstudyregister.com/files/pdf/23678.pdf (accessed 16 June 2009).

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Bateman 2008 {published data only}
  • Bateman ED, van Dyk M, Sagriotis A. Comparable spirometric efficacy of tiotropium compared with salmeterol plus fluticasone in patients with COPD: a pilot study. Pulmonary Pharmacology and Therapeutics 2008;21(1):20-5.
Biscione 2009 {published data only}
  • Biscione G, Crigna G, Auciello L, Pasqua F, Cazzola M. Addition of tiotropium (T) to a regular treatment with long-acting beta-agonist + inhaled corticosteroid (LABA + ICS) in patients with severe to very-severe COPD under in-patient pulmonary rehabilitation program (PRP) [Abstract]. European Respiratory Society Meeting, Vienna. 2009:[P526].
Dawber 2005 {published data only}
  • Dawber F, Tandy D, Haussermann S, Betz R. Efficacy of fluticasone/salmeterol propionate 50/500mcg bd versus tiotropium on lung function and mucociliary clearance in COPD patients [Abstract]. Respirology 2005;10(Suppl 3):A99.
  • GSK (SCO4011). A single centre, randomised, double-blind, double dummy, parallel group 3-week study to compare the effect of the fluticasone/salmeterol propionate combination 50/500mcg bd via the DISKUS™/ACCUHALER™ inhaler with tiotropium bromide 18 mcg od via the Handihaler inhaler on mucociliary clearance rate in patients with Chronic Obstructive Pulmonary Disease (COPD). http://www.gsk-clinicalstudyregister.com/files/pdf/23676.pdf (accessed 3 July 2009).
Golabi 2006 {published data only}
  • Golabi P, Topaloglu N, Karakurt S, Celikel T. Effects of tiotropium and fluticasone/salmeterol combination on lung hyperinflation dyspnea and exercise tolerance in COPD [Abstract]. European Respiratory Journal 2006;28(Suppl 50):33s [E304].
GSK 2009b {published data only}
  • GlaxoSmithKline. A single centre, randomised, double-blind, double dummy, parallel group 3-week study to compare the effect of the fluticasone/salmeterol propionate combination 50/500mcg bd via the DISKUS™/ACCUHALER™ inhaler with tiotropium bromide 18 mcg od via the Handihaler inhaler on mucociliary clearance rate in patients with Chronic Obstructive Pulmonary Disease (COPD). http://www.gsk-clinicalstudyregister.com 2009 (accessed 4 January 2013).
Hanania 2012 {published data only}
  • Hanania NA, Crater GD, Morris AN, Emmett AH, O'Dell DM, Niewoehner DE. Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD. Respiratory Medicine 2012;106(1):91-101.
  • Hanania NA, Niewoehner DE, Crater GD, Emmett A, Dell DO, Cicale Mi J. Triple therapy of fluticasone propionate/salmeterol combination 250/50 mcg and tiotropium improves lung function compared to tiotropium monotherapy [Abstract]. Chest. 2010; Vol. 138:867A.
Hara 2007 {published data only}
  • Hara K, Kurashima K, Tokunaga D, Ueno M, Aoyagi K, Isobe Z, et al. Single blind comparison of tiotropium and salmeterol plus fluticasone propionate of treatment in patients with chronic obstructive pulmonary disease (COPD) [Abstract]. American Thoracic Society International Conference, May 18-23, 2007, San Francisco, California, USA 2007:Poster #A1.
Hoshino 2011 {published data only}
Jung 2012 {published data only}
  • Jung KS, Park HY, Park SY, Kim SK, Kim YK, Shim JJ, et al. Comparison of tiotropium plus fluticasone propionate/salmeterol with tiotropium in COPD: A randomized controlled study. Respiratory Medicine 2012;106(3):382-9.
Kurashima 2009 {published data only}
Magnussen 2010 {published data only}
  • Magnussen H, Maltais F, Schmidt H, Kesten S, Metzdorf N. Comparison of tiotropium+salmeterol vs. fluticasone+salmeterol on lung volumes, exercise tolerance and locus of symptom limitation [Abstract]. American Journal of Respiratory and Critical Care Medicine. 2010; Vol. 181:A4472.
Maltais 2012 {published data only}
  • Maltais F, Mahler DA, Pepin V, Nadreau E, Crater G, Morris A. Effect of fluticasone-salmeterol combination+tiotropium vs tiotropium on exercise tolerance, the cause of exercise limitation and lung volumes in COPD [Abstract]. American Journal of Respiratory and Critical Care Medicine 2012;185(1):A2267.
Mittmann 2011 {published data only}
  • Mittmann N, Hernandez P, Mellstrom C, Brannman L, Welte T. Cost effectiveness of budesonide/formoterol added to tiotropium bromide versus placebo added to tiotropium bromide in patients with chronic obstructive pulmonary disease: Australian, Canadian and Swedish healthcare perspectives. Pharmacoeconomics 2011;29(5):403-14.
  • Mittmann N, Hernandez P, Mellström C, Brannman L, Welte T, Mellström C, et al. Cost-effectiveness of budesonide/formoterol added to tiotropium in COPD patients in Canada, Australia and Sweden [Abstract]. European Respiratory Society Annual Congress, Barcelona, Spain, September 18-22. 2010:[5183].
NCT00864812 {published data only}
  • NCT00864812. A randomized, open label, multicenter, phase 4 study for the comparison of efficacy of tiotropium plus salmeterol/ fluticasone propionate compared with tiotropium alone in COPD patients. http://clinicaltrials.gov/show/NCT00864812 2009.
NCT01124422 {published data only}
  • NCT01124422. A study of fluticasone propionate/salmeterol DISKUS combination product 250/50 mcg twice daily plus tiotropium 18 mcg daily versus placebo DISKUS twice daily plus tiotropium 18 mcg daily on exercise time and physiological parameters in subjects with chronic obstructive pulmonary disease. http://clinicaltrials.gov/show/NCT01124422 2010.
NCT01397890 {published data only}
  • NCT01397890. A randomised, parallel-group, open-label, multicentre, 3-month phase IV, efficacy and tolerability study of budesonide/formoterol (Symbicort® Turbuhaler® 160/4.5 μg/inhalation, 2 inhalations twice daily) added to tiotropium (SpirivaTM 18 μg/inhalation, 1 inhalation once daily) compared with tiotropium (SpirivaTM 18 μg/inhalation, 1 inhalation once daily) alone in severe chronic obstructive pulmonary disease (COPD) patients. http://clinicaltrials.gov/show/NCT01397890 2011.
Peters 2010 {published data only}
  • Peters SP, Kunselman SJ, Icitovic N, Moore WC, Pascual R, Ameredes BT, et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. New England Journal of Medicine 2010;363(18):1715-26.
Singh 2008 {published data only}
  • Singh D, Brooks J, Hagan G, Cahn A, O'Connor BJ. Superiority of "triple" therapy with fluticasone/salmeterol propionate and tiotropium bromide versus individual components in moderate to severe COPD. Thorax 2008;63(7):592-8.
Tanabe 2012 {published data only}
  • Tanabe N, Muro S, Oguma T, Sato S, Kiyokawa H, Takahashi T, et al. Computed tomography assessment of pharmacological lung volume reduction induced by bronchodilators in COPD. COPD 2012;9:401-8.
Welte 2009c {published data only}
  • Welte T, Hartman L, Polanowski T, Hernandez P, Miravitlles M, Peterson S, et al. Budesonide/formoterol added to tiotropium is well tolerated and reduces risk of severe exacerbations in COPD patients [Abstract]. American Journal of Respiratory and Critical Care Medicine 2009;179:A6188.
  • Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, et al. Addition of budesonide/formoterol to tiotropium reduces the number of exacerbation days compared with tiotropium alone [Abstract]. Chest 2009;136(4):26S-f.
  • Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, et al. Budesonide/formoterol added to tiotropium provides rapid improvements in lung function and ability to undertake morning activities [Abstract]. Chest 2009; Vol. 136, issue 4:24S-g.
  • Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, et al. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine 2009;180(8):741-50.
  • Welte T, Miravitlles M, Hernandez P, Peterson S, Polanowski T, Kessler R, et al. Budesonide/formoterol added to tiotropium improves exacerbations and exacerbation-related antibiotic use in patients with COPD [Abstract]. European Respiratory Society. 2009:[P2012].
Williamson 2010 {published data only}
  • Williamson PA, Short PM, Clearie KL, Vaidyanathan S, Fardon TC, Howaniec LJ, et al. Paradoxical trough effects of triple therapy with budesonide/formoterol and tiotropium bromide on pulmonary function outcomes in COPD. Chest 2010;138(3):595-604.

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
NCT01513460 {published data only}
  • NCT01513460. A multicenter, randomized, blinded, active-controlled, parallel-group study to compare the efficacy, tolerability and safety of NVA237 compared to tiotropium added on to fluticasone/salmeterol in patients with chronic obstructive pulmonary disease. http://clinicaltrials.gov/show/NCT01513460 2012.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
Appleton 2006a
  • Appleton S, Poole P, Smith B, Veale A, Lasserson TJ, Chan MMK, et al. Long-acting beta2-agonists for poorly reversible chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD001104.pub2]
Appleton 2006b
  • Appleton S, Jones T, Poole P, Pilotto L, Adams R, Lasserson TJ, et al. Ipratropium bromide versus short acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 2. [DOI: 10.1002/14651858.CD001387.pub2]
Appleton 2006c
  • Appleton S, Jones T, Poole P, Lasserson TJ, Adams R, Smith B, et al. Ipratropium bromide versus long-acting beta-2 agonists for stable chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD006101]
Barr 2005
Calverley 2003
  • Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. European Respiratory Journal 2003;22(6):912-9.
Chong 2012
Cochrane Handbook
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated September 2008]. The Cochrane Collaboration, 2008. Available from www.cochrane-handbook.org (accessed 26 February 2009).
Effing 2007
GOLD
  • Global Initiative for Chronic Obstructive Lung Disease. http://www.goldcopd.com (accessed 18 February 2009).
ICHE2a 1995
  • Expert Working Group (Efficacy) of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Clinical safety data management: Definitions and standards for expedited reporting. http://www.fda.gov/cder/guidance/iche2a.pdf 1995.
Jones 2009
  • Jones PW. Triple therapy for chronic obstructive pulmonary disease: trials catching up with clinical practice?. American Journal of Respiratory and Critical Care Medicine 2009;180(8):689-90.
Karner 2011
  • Karner C, Cates CJ. Combination inhaled steroid and long-acting beta2-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2011, Issue 3. [DOI: 10.1002/14651858.CD008532.pub2]
Karner 2011a
Karner 2012
  • Karner C, Cates CJ. Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2012, Issue 4. [DOI: 10.1002/14651858.CD008989.pub2]
Karner 2012a
Keene 2008
  • Keene ON, Calverley PMA, Jones PW, Vestbo J, Anderson JA. Statistical analysis of exacerbation rates in COPD: TRISTAN and ISOLDE revisited. European Respiratory Journal 2008;32:17–24.
Kesten 2007
Lacasse 2006
Nannini 2007a
  • Nannini LJ, Cates CJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta2-agonist in one inhaler versus placebo for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD003794.pub3]
Nannini 2007b
  • Nannini LJ, Cates CJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta2-agonist in one inhaler versus inhaled steroids for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006826]
Nannini 2012
RevMan 2012
  • The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
SGRQ
  • Jones P. St George Respiratory Questionnaire. http://www.healthstatus.sgul.ac.uk/downloads/respiratory_questionairre.htm (accessed 6 October 2009).
Singh 2008b
  • Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA 2008;300(12):1439-50.
Singh 2009
  • Singh S, Amin AV, Loke YK. Long-term use of inhaled corticosteroids and the risk of pneumonia in chronic obstructive pulmonary disease. Archives of Internal Medicine 2009;169(3):219-29.
Spencer 2011
  • Spencer S, Karner C, Cates CJ, Evans DJ. Inhaled corticosteroids versus long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2011, Issue 12. [DOI: 10.1002/14651858.CD007033.pub3]
Suissa 2008
Suissa 2008a
  • Suissa S. Methodologic shortcomings of the INSPIRE randomized trial. American Journal of Respiratory and Critical Care Medicine 2008;178(10):1090-1.
TORCH
  • Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. New England Journal of Medicine 2007;356(8):775-89. [1533-4406: (Electronic)]
UPLIFT
Yang 2012