Display options
Cite
Mills EJ, Druyts E, Ghement I, et al. Pharmacotherapies for chronic obstructive pulmonary disease: a multiple treatment comparison meta-analysis. Clin Epidemiol. 2011;3:107-29doi: 10.2147/CLEP.S16235.
Mills, E. J., Druyts, E., Ghement, I., & Puhan, M. A. (2011). Pharmacotherapies for chronic obstructive pulmonary disease: a multiple treatment comparison meta-analysis. Clinical epidemiology, 3107-29. https://doi.org/10.2147/CLEP.S16235
Mills, Edward J, et al. "Pharmacotherapies for chronic obstructive pulmonary disease: a multiple treatment comparison meta-analysis." Clinical epidemiology vol. 3 (2011): 107-29. doi: https://doi.org/10.2147/CLEP.S16235
Mills EJ, Druyts E, Ghement I, Puhan MA. Pharmacotherapies for chronic obstructive pulmonary disease: a multiple treatment comparison meta-analysis. Clin Epidemiol. 2011 Mar 28;3:107-29. doi: 10.2147/CLEP.S16235. PMID: 21487451; PMCID: PMC3072154.
Copy Download .nbib Format: NLM
Share it on

Clin Epidemiol. 2011 Mar 28;3:107-29. doi: 10.2147/CLEP.S16235.

Pharmacotherapies for chronic obstructive pulmonary disease: a multiple treatment comparison meta-analysis.

Clinical epidemiology

Edward J Mills, Eric Druyts, Isabella Ghement, Milo A Puhan

Affiliations

  1. Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada;

PMID: 21487451 PMCID: PMC3072154 DOI: 10.2147/CLEP.S16235

Abstract

BACKGROUND: Most patients with moderate and severe chronic obstructive pulmonary disease (COPD) receive long-acting bronchodilators (LABA) for symptom control. It is, however, unclear if and what drug treatments should be added to LABAs to reduce exacerbations, which is an important goal of COPD management. Since current guidelines cannot make strong recommendations yet, our aim was to determine the relative efficacy of existing treatments and combinations to reduce the risk for COPD exacerbations.

METHODS: We included randomized clinical trials (RCTs) evaluating long-acting β(2) agonists (LABA), long-acting muscarinic antagonists (LAMA), inhaled glucocorticosterioids (ICS), and the phosphodiesterase-4 (PDE4) inhibitor roflumilast, and combinations of these interventions in moderate to severe COPD populations. Our primary outcome was the event rate of exacerbations. We conducted a random-effects Bayesian mixed-treatment comparison (MTC) and applied several sensitivity analyses. In particular, we confirmed our findings using a binomial MTC analysis examining whether a patient experienced at least one exacerbation event or not during the trial. We also used an additive assumption to calculate the combined effects of treatments that were not included in the systematic review.

RESULTS: Twenty-six studies provided data on the total number of exacerbations and/or the mean annual rate of exacerbations among a combined 36,312 patients. There were a total of 10 treatment combinations in the MTC and 15 in the additive analysis. Compared with all other treatments, the combination of roflumilast plus LAMA exhibited the largest treatment effects, and had the highest probability (45%) of being the best first-line treatment. This was consistent whether applying the incidence rate analysis or the binomial analysis. When applying the additive assumption, most point estimates suggested that roflumilast may provide additional benefit by further reducing exacerbations.

CONCLUSIONS: Using various meta-analytic approaches, our study demonstrates that depending on the choice of drug, combined treatments offer a therapeutic advantage.

Keywords: MTC analysis; clinical trials; exacerbations; roflumilast

References

  1. Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1136-42 - PubMed
  2. Am J Respir Crit Care Med. 2002 Nov 15;166(10):1358-63 - PubMed
  3. Eur Respir J. 2000 May;15(5):878-85 - PubMed
  4. Lancet. 2009 Aug 29;374(9691):695-703 - PubMed
  5. Eur Respir J. 2002 Feb;19(2):217-24 - PubMed
  6. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD006829 - PubMed
  7. Clin Ther. 2008 Aug;30(8):1416-25 - PubMed
  8. Am J Respir Crit Care Med. 1996 Feb;153(2):616-21 - PubMed
  9. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD002991 - PubMed
  10. Am J Respir Crit Care Med. 2006 Apr 1;173(7):736-43 - PubMed
  11. Control Clin Trials. 1986 Sep;7(3):177-88 - PubMed
  12. Eur Respir J. 1997 Apr;10(4):815-21 - PubMed
  13. Ann Intern Med. 2008 Apr 1;148(7):544-53 - PubMed
  14. N Engl J Med. 2008 Oct 9;359(15):1543-54 - PubMed
  15. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD006826 - PubMed
  16. Chest. 2002 Apr;121(4):1058-69 - PubMed
  17. Respir Med. 2008 Aug;102(8):1099-108 - PubMed
  18. Am J Respir Crit Care Med. 2008 Jan 1;177(1):19-26 - PubMed
  19. BMC Med. 2009 Jan 14;7:2 - PubMed
  20. Ann Intern Med. 2005 Sep 6;143(5):317-26 - PubMed
  21. Am J Respir Crit Care Med. 2002 Oct 15;166(8):1084-91 - PubMed
  22. Lancet. 1998 Mar 14;351(9105):773-80 - PubMed
  23. Stat Med. 1996 Dec 30;15(24):2733-49 - PubMed
  24. Pulm Pharmacol Ther. 2003;16(4):241-6 - PubMed
  25. Clin Ther. 2007 Feb;29(2):261-78 - PubMed
  26. Am J Respir Crit Care Med. 2001 Sep 1;164(5):778-84 - PubMed
  27. Ann Intern Med. 2009 Oct 20;151(8):517-27 - PubMed
  28. Lancet. 2005 Aug 13-19;366(9485):563-71 - PubMed
  29. Thorax. 2003 May;58(5):399-404 - PubMed
  30. Thorax. 2003 Oct;58(10):855-60 - PubMed
  31. Am J Respir Crit Care Med. 2007 Jan 15;175(2):144-9 - PubMed
  32. Chest. 2003 Sep;124(3):834-43 - PubMed
  33. Am J Gastroenterol. 2004 Dec;99(12):2297-301 - PubMed
  34. PLoS Med. 2007 May;4(5):e112 - PubMed
  35. Thorax. 2006 Feb;61(2):122-8 - PubMed
  36. N Engl J Med. 2007 Feb 22;356(8):775-89 - PubMed
  37. COPD. 2009 Feb;6(1):17-25 - PubMed
  38. Respir Med. 2008 Nov;102(11):1511-20 - PubMed
  39. Respir Res. 2011 Jan 27;12:18 - PubMed
  40. Drugs. 2009;69(5):549-65 - PubMed
  41. Eur Respir J. 2007 Sep;30(3):472-8 - PubMed
  42. Lancet. 2003 Feb 8;361(9356):449-56 - PubMed
  43. Pharmacoeconomics. 2008;26(9):753-67 - PubMed
  44. Eur Respir J. 2003 Dec;22(6):912-9 - PubMed
  45. Stat Med. 2004 Oct 30;23(20):3105-24 - PubMed
  46. Can Respir J. 2002 May-Jun;9(3):178-85 - PubMed
  47. Chest. 2000 May;117(5 Suppl 2):398S-401S - PubMed
  48. Int J Chron Obstruct Pulmon Dis. 2008;3(2):301-10 - PubMed
  49. Eur Respir J. 2003 Jan;21(1):74-81 - PubMed
  50. Respiration. 2006;73(5):603-9 - PubMed
  51. Pharmacotherapy. 2005 Dec;25(12):1708-18 - PubMed
  52. Chest. 1999 Apr;115(4):957-65 - PubMed
  53. Respir Med. 2005 Dec;99(12):1511-20 - PubMed
  54. BMJ. 2000 May 13;320(7245):1297-303 - PubMed
  55. Respir Res. 2007 Jul 02;8:45 - PubMed
  56. Eur Respir J. 2002 Nov;20(5):1138-46 - PubMed
  57. Thorax. 1998 Jun;53(6):477-82 - PubMed
  58. Pneumologie. 2006 Jun;60(6):341-6 - PubMed
  59. Ann Intern Med. 2007 Nov 6;147(9):639-53 - PubMed
  60. Thorax. 2008 Feb;63(2):122-8 - PubMed
  61. Lancet. 2009 Aug 29;374(9691):685-94 - PubMed
  62. Chest. 2006 Sep;130(3):647-56 - PubMed
  63. Chest. 2000 Nov;118(5):1294-302 - PubMed
  64. Can Respir J. 2007 Nov-Dec;14(8):465-72 - PubMed
  65. Am J Epidemiol. 2009 May 1;169(9):1158-65 - PubMed
  66. Chest. 2007 Dec;132(6):1756-63 - PubMed
  67. COPD. 2009 Oct;6(5):320-9 - PubMed
  68. Respiration. 2006;73(4):420-7 - PubMed
  69. JAMA. 2003 Nov 5;290(17):2301-12 - PubMed
  70. Pharmacotherapy. 2009 Aug;29(8):891-905 - PubMed
  71. Am J Respir Crit Care Med. 2001 Apr;163(5):1087-92 - PubMed
  72. Eur Respir J. 2004 Jun;23(6):832-40 - PubMed
  73. Chest. 2002 Jul;122(1):47-55 - PubMed
  74. Respir Med. 2003 Jan;97 Suppl A:S35-43 - PubMed
  75. Am J Respir Crit Care Med. 2006 Apr 15;173(8):842-6 - PubMed
  76. Arch Intern Med. 2006 Jun 26;166(12):1269-75 - PubMed
  77. Eur Respir J. 2005 Aug;26(2):214-22 - PubMed
  78. Eur Respir J. 2006 Mar;27(3):547-55 - PubMed
  79. Am J Respir Crit Care Med. 2007 Jul 15;176(2):154-61 - PubMed
  80. Clin Exp Allergy. 1999 Jun;29 Suppl 2:125-8 - PubMed
  81. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD003794 - PubMed
  82. Ann Intern Med. 2007 Apr 17;146(8):545-55 - PubMed
  83. Am J Respir Crit Care Med. 2002 Jun 15;165(12):1592-6 - PubMed

Publication Types