Comparisons of exacerbations and mortality among regular inhaled therapies for patients with stable chronic obstructive pulmonary disease: Systematic review and Bayesian network meta-analysis

English version

Autoři: Hyun Woo Lee ^aff001; Jimyung Park ^aff001; Junwoo Jo ^aff002; Eun Jin Jang ^aff003; Chang-Hoon Lee ^aff001
Působiště autorů: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea ^aff001; Department of Statistics, Kyungpook National University, Daegu, South Korea ^aff002; Department of Information Statistics, Andong National University, Andong, South Korea ^aff003
Vyšlo v časopise: Comparisons of exacerbations and mortality among regular inhaled therapies for patients with stable chronic obstructive pulmonary disease: Systematic review and Bayesian network meta-analysis. PLoS Med 16(11): e32767. doi:10.1371/journal.pmed.1002958
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1002958

Souhrn

Background

Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined.

Methods and findings

We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50–0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59–0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76–0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19–2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk.

Conclusions

These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.

Klíčová slova:

Adverse events – Death rates – Chronic obstructive pulmonary disease – Network analysis – Pneumonia – Pulmonology – Systematic reviews

Zdroje

1. Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT, et al. Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. The New England journal of medicine. 2016;374(23):2222–34. Epub 2016/05/18. doi: 10.1056/NEJMoa1516385 27181606.

2. Lipson DA, Barnhart F, Brealey N, Brooks J, Criner GJ, Day NC, et al. Once-Daily Single-Inhaler Triple versus Dual Therapy in Patients with COPD. The New England journal of medicine. 2018;378(18):1671–80. Epub 2018/04/19. doi: 10.1056/NEJMoa1713901 29668352.

3. Papi A, Vestbo J, Fabbri L, Corradi M, Prunier H, Cohuet G, et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet (London, England). 2018;391(10125):1076–84. Epub 2018/02/13. doi: 10.1016/s0140-6736(18)30206-x 29429593.

4. Zheng Y, Zhu J, Liu Y, Lai W, Lin C, Qiu K, et al. Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis. BMJ (Clinical research ed). 2018;363:k4388. Epub 2018/11/08. doi: 10.1136/bmj.k4388 30401700.

5. Tricco AC, Strifler L, Veroniki AA, Yazdi F, Khan PA, Scott A, et al. Comparative safety and effectiveness of long-acting inhaled agents for treating chronic obstructive pulmonary disease: a systematic review and network meta-analysis. BMJ open. 2015;5(10):e009183. Epub 2015/10/28. doi: 10.1136/bmjopen-2015-009183 26503392

6. Oba Y, Keeney E, Ghatehorde N, Dias S. Dual combination therapy versus long-acting bronchodilators alone for chronic obstructive pulmonary disease (COPD): a systematic review and network meta-analysis. The Cochrane database of systematic reviews. 2018;12:Cd012620. Epub 2018/12/07. doi: 10.1002/14651858.CD012620.pub2 30521694.

7. Aziz MIA, Tan LE, Wu DB, Pearce F, Chua GSW, Lin L, et al. Comparative efficacy of inhaled medications (ICS/LABA, LAMA, LAMA/LABA and SAMA) for COPD: a systematic review and network meta-analysis. International journal of chronic obstructive pulmonary disease. 2018;13:3203–31. Epub 2018/10/24. doi: 10.2147/COPD.S173472 30349228

8. 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. The New England journal of medicine. 2007;356(8):775–89. Epub 2007/02/23. doi: 10.1056/NEJMoa063070 17314337.

9. Lee CH, Jang EJ, Hyun MK, Lee NR, Kim K, Yim JJ. Risk of hospital admission or emergency room visit for pneumonia in patients using respiratory inhalers: a case-crossover study. Respirology (Carlton, Vic). 2013;18(7):1116–27. Epub 2013/05/29. doi: 10.1111/resp.12127 23711281.

10. Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. The Cochrane database of systematic reviews. 2014;(3):Cd010115. Epub 2014/03/13. doi: 10.1002/14651858.CD010115.pub2 24615270.

11. Gershon A, Croxford R, Calzavara A, To T, Stanbrook MB, Upshur R, et al. Cardiovascular safety of inhaled long-acting bronchodilators in individuals with chronic obstructive pulmonary disease. JAMA internal medicine. 2013;173(13):1175–85. Epub 2013/05/22. doi: 10.1001/jamainternmed.2013.1016 23689820.

12. Dong YH, Lin HH, Shau WY, Wu YC, Chang CH, Lai MS. Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials. Thorax. 2013;68(1):48–56. Epub 2012/10/09. doi: 10.1136/thoraxjnl-2012-201926 23042705.

13. Jansen JP, Crawford B, Bergman G, Stam W. Bayesian meta-analysis of multiple treatment comparisons: an introduction to mixed treatment comparisons. Value in health: the journal of the International Society for Pharmacoeconomics and Outcomes Research. 2008;11(5):956–64. Epub 2008/05/21. doi: 10.1111/j.1524-4733.2008.00347.x 18489499.

14. Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Annals of internal medicine. 2015;162(11):777–84. Epub 2015/06/02. doi: 10.7326/M14-2385 26030634.

15. Spiegelhalter DJ, Myles JP, Jones DR, Abrams KR. Bayesian methods in health technology assessment: a review. Health technology assessment (Winchester, England). 2000;4(38):1–130. Epub 2001/01/03. 11134920.

16. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. Epub 2009/07/22. doi: 10.1371/journal.pmed.1000097 19621072

17. Seo HJ, Kim SY, Lee YJ, Jang BH, Park JE, Sheen SS, et al. A newly developed tool for classifying study designs in systematic reviews of interventions and exposures showed substantial reliability and validity. Journal of clinical epidemiology. 2016;70:200–5. Epub 2015/09/27. doi: 10.1016/j.jclinepi.2015.09.013 26408805.

18. McGowan J, Sampson M, Salzwedel DM, Cogo E, Foerster V, Lefebvre C. PRESS Peer Review of Electronic Search Strategies: 2015 Guideline Statement. Journal of clinical epidemiology. 2016;75:40–6. Epub 2016/03/24. doi: 10.1016/j.jclinepi.2016.01.021 27005575.

19. Liu Z, Rich B, Hanley JA. Recovering the raw data behind a non-parametric survival curve. Systematic reviews. 2014;3:151. Epub 2015/01/01. doi: 10.1186/2046-4053-3-151 25551437

20. Mackay AJ, Donaldson GC, Patel AR, Singh R, Kowlessar B, Wedzicha JA. Detection and severity grading of COPD exacerbations using the exacerbations of chronic pulmonary disease tool (EXACT). The European respiratory journal. 2014;43(3):735–44. Epub 2013/08/31. doi: 10.1183/09031936.00110913 23988767.

21. Burge S, Wedzicha JA. COPD exacerbations: definitions and classifications. The European respiratory journal Supplement. 2003;41:46s–53s. Epub 2003/06/11. 12795331.

22. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Clinical research ed). 2011;343:d5928. Epub 2011/10/20. doi: 10.1136/bmj.d5928 22008217

23. Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Statistics in medicine. 2004;23(20):3105–24. Epub 2004/09/28. doi: 10.1002/sim.1875 15449338.

24. Salanti G, Ades AE, Ioannidis JP. Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. Journal of clinical epidemiology. 2011;64(2):163–71. Epub 2010/08/07. doi: 10.1016/j.jclinepi.2010.03.016 20688472.

25. Dias S, Sutton AJ, Welton NJ, Ades AE. Evidence synthesis for decision making 3: heterogeneity—subgroups, meta-regression, bias, and bias-adjustment. Medical decision making: an international journal of the Society for Medical Decision Making. 2013;33(5):618–40. Epub 2013/06/28. doi: 10.1177/0272989x13485157 23804507

26. Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Statistics in medicine. 2010;29(7–8):932–44. Epub 2010/03/10. doi: 10.1002/sim.3767 20213715.

27. Cazzola M, Rogliani P, Calzetta L, Matera MG. Triple therapy versus single and dual long-acting bronchodilator therapy in COPD: a systematic review and meta-analysis. The European respiratory journal. 2018;52(6). Epub 2018/10/13. doi: 10.1183/13993003.01586-2018 30309975.

28. Calzetta L, Cazzola M, Matera MG, Rogliani P. Adding a LAMA to ICS/LABA Therapy: A Meta-analysis of Triple Combination Therapy in COPD. Chest. 2019;155(4):758–70. Epub 2019/01/21. doi: 10.1016/j.chest.2018.12.016 30660781.

29. McGarvey LP, Magder S, Burkhart D, Kesten S, Liu D, Manuel RC, et al. Cause-specific mortality adjudication in the UPLIFT(R) COPD trial: findings and recommendations. Respiratory medicine. 2012;106(4):515–21. Epub 2011/11/22. doi: 10.1016/j.rmed.2011.10.009 22100536.

30. Schmidt SA, Johansen MB, Olsen M, Xu X, Parker JM, Molfino NA, et al. The impact of exacerbation frequency on mortality following acute exacerbations of COPD: a registry-based cohort study. BMJ open. 2014;4(12):e006720. Epub 2014/12/21. doi: 10.1136/bmjopen-2014-006720 25526796

31. Donaldson GC, Hurst JR, Smith CJ, Hubbard RB, Wedzicha JA. Increased risk of myocardial infarction and stroke following exacerbation of COPD. Chest. 2010;137(5):1091–7. Epub 2009/12/22. doi: 10.1378/chest.09-2029 20022970.

32. McAllister DA, Maclay JD, Mills NL, Leitch A, Reid P, Carruthers R, et al. Diagnosis of myocardial infarction following hospitalisation for exacerbation of COPD. The European respiratory journal. 2012;39(5):1097–103. Epub 2012/02/11. doi: 10.1183/09031936.00124811 22323574.

33. Rothnie KJ, Connell O, Mullerova H, Smeeth L, Pearce N, Douglas I, et al. Myocardial Infarction and Ischemic Stroke after Exacerbations of Chronic Obstructive Pulmonary Disease. Annals of the American Thoracic Society. 2018;15(8):935–46. Epub 2018/05/04. doi: 10.1513/AnnalsATS.201710-815OC 29723057

34. Kunisaki KM, Dransfield MT, Anderson JA, Brook RD, Calverley PMA, Celli BR, et al. Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial. American journal of respiratory and critical care medicine. 2018;198(1):51–7. Epub 2018/02/15. doi: 10.1164/rccm.201711-2239OC 29442524.

35. Wedzicha JA, Singh R, Mackay AJ. Acute COPD exacerbations. Clinics in chest medicine. 2014;35(1):157–63. Epub 2014/02/11. doi: 10.1016/j.ccm.2013.11.001 24507843.

36. Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57(10):847–52. Epub 2002/09/27. doi: 10.1136/thorax.57.10.847 12324669

37. Lee CH, Choi S, Jang EJ, Yang HM, Il Yoon H, Kim YJ, et al. Inhaled bronchodilators and acute myocardial infarction: a nested case-control study. Scientific reports. 2017;7(1):17915. Epub 2017/12/22. doi: 10.1038/s41598-017-17890-1 29263396

38. Sin DD, Tashkin D, Zhang X, Radner F, Sjobring U, Thoren A, et al. Budesonide and the risk of pneumonia: a meta-analysis of individual patient data. Lancet (London, England). 2009;374(9691):712–9. Epub 2009/09/01. doi: 10.1016/s0140-6736(09)61250-2 19716963.

39. Janson C, Larsson K, Lisspers KH, Stallberg B, Stratelis G, Goike H, et al. Pneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting beta2 agonist: observational matched cohort study (PATHOS). BMJ (Clinical research ed). 2013;346:f3306. Epub 2013/05/31. doi: 10.1136/bmj.f3306 23719639

40. Finney L, Berry M, Singanayagam A, Elkin SL, Johnston SL, Mallia P. Inhaled corticosteroids and pneumonia in chronic obstructive pulmonary disease. The Lancet Respiratory medicine. 2014;2(11):919–32. Epub 2014/09/23. doi: 10.1016/S2213-2600(14)70169-9 25240963.

41. Chen D, Restrepo MI, Fine MJ, Pugh MJ, Anzueto A, Metersky ML, et al. Observational study of inhaled corticosteroids on outcomes for COPD patients with pneumonia. American journal of respiratory and critical care medicine. 2011;184(3):312–6. Epub 2011/04/23. doi: 10.1164/rccm.201012-2070OC 21512168

42. Sellares J, Lopez-Giraldo A, Lucena C, Cilloniz C, Amaro R, Polverino E, et al. Influence of previous use of inhaled corticoids on the development of pleural effusion in community-acquired pneumonia. American journal of respiratory and critical care medicine. 2013;187(11):1241–8. Epub 2013/04/18. doi: 10.1164/rccm.201209-1732OC 23590264.

43. Festic E, Scanlon PD. Incident pneumonia and mortality in patients with chronic obstructive pulmonary disease. A double effect of inhaled corticosteroids? American journal of respiratory and critical care medicine. 2015;191(2):141–8. Epub 2014/11/20. doi: 10.1164/rccm.201409-1654PP 25409118

44. Bero LA. Why the Cochrane risk of bias tool should include funding source as a standard item. The Cochrane database of systematic reviews. 2013;(12):Ed000075. Epub 2014/02/28. doi: 10.1002/14651858.ED000075 24575439.

45. Sterne JA. Why the Cochrane risk of bias tool should not include funding source as a standard item. The Cochrane database of systematic reviews. 2013;(12):Ed000076. Epub 2014/02/28. doi: 10.1002/14651858.ED000076 24575440.

46. Sutton AJ, Cooper NJ, Lambert PC, Jones DR, Abrams KR, Sweeting MJ. Meta-analysis of rare and adverse event data. Expert review of pharmacoeconomics & outcomes research. 2002;2(4):367–79. Epub 2002/08/01. doi: 10.1586/14737167.2.4.367 19807443.