Efficacy of ICS versus Non-ICS Combination Therapy in COPD: A Meta-Analysis of Randomised Controlled Trials

References

• GOLD-2020-REPORT-ver1.0wms.pdf [Internet]. [cited December 9, 2021]. Available from: https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.0wms.pdf. Accessed April 19, 2022.
   Google Scholar
• Anzueto A. Impact of exacerbations on COPD. Eur Respir Rev. 2010;19(116):113–118. doi:10.1183/09059180.00002610
   PubMedGoogle Scholar
• May SM, Li JTC. Burden of chronic obstructive pulmonary disease: healthcare costs and beyond. Allergy Asthma Proc. 2015;36(1):4–10. doi:10.2500/aap.2015.36.3812
   PubMed Web of Science ®Google Scholar
• Halpin DM, Miravitlles M, Metzdorf N, Celli B. Impact and prevention of severe exacerbations of COPD: a review of the evidence. Int J Chron Obstruct Pulmon Dis. 2017;12:2891–2908. doi:10.2147/COPD.S139470
   PubMed Web of Science ®Google Scholar
• Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study - PubMed [Internet]. [cited December 9, 2021]. Available from: https://pubmed.ncbi.nlm.nih.gov/24321804/. Accessed April 19, 2022.
   Google Scholar
• Magnussen H, Watz H, Kirsten A, et al. Stepwise withdrawal of inhaled corticosteroids in COPD patients receiving dual bronchodilation: WISDOM study design and rationale. Respir Med. 2014;108(4):593–599. doi:10.1016/j.rmed.2014.01.002
   PubMed Web of Science ®Google Scholar
• Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. N Engl J Med. 2016;374(23):2222–2234. doi:10.1056/NEJMoa1516385
   PubMed Web of Science ®Google Scholar
• Lipson DA, Barnhart F, Brealey N, et al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. N Engl J Med. 2018;378(18):1671–1680. doi:10.1056/NEJMoa1713901
   PubMed Web of Science ®Google Scholar
• Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial - PubMed [Internet]. [cited December 9, 2021]. Available from: https://pubmed.ncbi.nlm.nih.gov/29429593/. Accessed April 19, 2022.
   Google Scholar
• Welte T, Miravitlles M, Hernandez P, et al. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;180(8):741–750. doi:10.1164/rccm.200904-0492OC
   PubMed Web of Science ®Google Scholar
• Superiority of “triple” therapy with salmeterol/fluticasone propionate and tiotropium bromide versus individual components in moderate to severe COPD - PubMed [Internet]. [cited December 9, 2021]. Available from: https://pubmed.ncbi.nlm.nih.gov/18245142/. Accessed April 19, 2022.
   Google Scholar
• Frith PA, Thompson PJ, Ratnavadivel R, et al. Glycopyrronium once-daily significantly improves lung function and health status when combined with salmeterol/fluticasone in patients with COPD: the GLISTEN study - A randomised controlled trial. Thorax. 2015;70(6):519–527. doi:10.1136/thoraxjnl-2014-206670
   PubMed Web of Science ®Google Scholar
• Singh D, Papi A, Corradi M, et al. Single inhaler triple therapy versus inhaled corticosteroid plus long-acting β2-agonist therapy for chronic obstructive pulmonary disease (TRILOGY): a double-blind, parallel group, randomised controlled trial. Lancet. 2016;388(10048):963–973. doi:10.1016/S0140-6736(16)31354-X
   PubMed Web of Science ®Google Scholar
• Ferguson GT, Rabe KF, Martinez FJ, et al. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, Phase 3 randomised controlled trial. Lancet Respir Med. 2018;6(10):747–758. doi:10.1016/S2213-2600(18)30327-8
   PubMed Web of Science ®Google Scholar
• Cazzola M, Di Lorenzo G, Di Perna F, Calderaro F, Testi R, Centanni S. Additive effects of salmeterol and fluticasone or theophylline in COPD. Chest. 2000;118(6):1576–1581. doi:10.1378/chest.118.6.1576
   PubMed Web of Science ®Google Scholar
• Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2003;361(9356):449–456. doi:10.1016/S0140-6736(03)12459-2
   PubMed Web of Science ®Google Scholar
• Calverley PM, Boonsawat W, Cseke Z, Zhong N, Peterson S, Olsson H. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J. 2003;22(6):912–919. doi:10.1183/09031936.03.00027003
   PubMed Web of Science ®Google Scholar
• O’Donnell DE, Sciurba F, Celli B, et al. Effect of fluticasone propionate/salmeterol on lung hyperinflation and exercise endurance in COPD. Chest. 2006;130(3):647–656. doi:10.1378/chest.130.3.647
   PubMed Web of Science ®Google Scholar
• Kardos P, Wencker M, Glaab T, Vogelmeier C. Impact of salmeterol/fluticasone propionate versus salmeterol on exacerbations in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175(2):144–149. doi:10.1164/rccm.200602-244OC
   PubMed Web of Science ®Google Scholar
• Calverley PMA, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356(8):775–789. doi:10.1056/NEJMoa063070
   PubMed Web of Science ®Google Scholar
• Efficacy and safety of budesonide and formoterol in one pressurized metered-dose inhaler in patients with moderate to very severe chronic obstructive pulmonary disease. Springerlink. [cited December 9, 2021]. Available from: https://link.springer.com/article/10.2165/00003495-200868140-00004. Accessed April 19, 2022.
   Google Scholar
• Ferguson GT, Anzueto A, Fei R, Emmett A, Knobil K, Kalberg C. Effect of fluticasone propionate/salmeterol (250/50μg) or salmeterol (50μg) on COPD exacerbations. Respir Med. 2008;102(8):1099–1108. doi:10.1016/j.rmed.2008.04.019
   PubMed Web of Science ®Google Scholar
• Anzueto A, Ferguson GT, Feldman G, et al. Effect of fluticasone propionate/salmeterol (250/50) on COPD exacerbations and impact on patient outcomes. COPD. 2009;6(5):320–329. doi:10.1080/15412550903140881
   PubMedGoogle Scholar
• Rennard SI, Tashkin DP, McElhattan J, et al. Efficacy and tolerability of budesonide/formoterol in one hydrofluoroalkane pressurized metered-dose inhaler in patients with chronic obstructive pulmonary disease. Drugs. 2009;69(5):549–565. doi:10.2165/00003495-200969050-00004
   PubMed Web of Science ®Google Scholar
• Calverley PMA, Kuna P, Monsó E, et al. Beclomethasone/formoterol in the management of COPD: a randomised controlled trial. Respir Med. 2010;104(12):1858–1868. doi:10.1016/j.rmed.2010.09.008
   PubMed Web of Science ®Google Scholar
• Sharafkhaneh A, Southard JG, Goldman M, Uryniak T, Martin UJ. Effect of budesonide/formoterol pMDI on COPD exacerbations: a double-blind, randomized study. Respir Med. 2012;106(2):257–268. doi:10.1016/j.rmed.2011.07.020
   PubMed Web of Science ®Google Scholar
• Efficacy and safety characteristics of mometasone furoate/formoterol fumarate fixed-dose combination in subjects with moderate to very severe COPD: findings from pooled analysis of two randomized, 52-week placebo-controlled trials - PubMed [Internet]. [cited December 9, 2021]. Available from: https://pubmed.ncbi.nlm.nih.gov/22334770/. Accessed April 19, 2022.
   Google Scholar
• Kerwin EM, Scott-Wilson C, Sanford L, et al. A randomised trial of fluticasone furoate/vilanterol (50/25 μg; 100/25 μg) on lung function in COPD. Respir Med. 2013;107(4):560–569. doi:10.1016/j.rmed.2012.12.014
   PubMed Web of Science ®Google Scholar
• Fukuchi Y, Samoro R, Fassakhov R, et al. Budesonide/formoterol via Turbuhaler® versus formoterol via Turbuhaler® in patients with moderate to severe chronic obstructive pulmonary disease: Phase III multinational study results. Respirology. 2013;18(5):866–873. doi:10.1111/resp.12090
   PubMed Web of Science ®Google Scholar
• Dransfield MT, Bourbeau J, Jones PW, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med. 2013;1(3):210–223. doi:10.1016/S2213-2600(13)70040-7
   PubMed Web of Science ®Google Scholar
• Martinez FJ, Boscia J, Feldman G, et al. Fluticasone furoate/vilanterol (100/25; 200/25 μg) improves lung function in COPD: a randomised trial. Respir Med. 2013;107(4):550–559. doi:10.1016/j.rmed.2012.12.016
   PubMed Web of Science ®Google Scholar
• Wedzicha JA, Singh D, Vestbo J, et al. Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations. Respir Med. 2014;108(8):1153–1162. doi:10.1016/j.rmed.2014.05.013
   PubMed Web of Science ®Google Scholar
• Rossi A, van der Molen T, Del Olmo R, et al. INSTEAD: a randomised switch trial of indacaterol versus salmeterol/fluticasone in moderate COPD. Eur Respir J. 2014;44(6):1548–1556. doi:10.1183/09031936.00126814
   PubMed Web of Science ®Google Scholar
• Bhatt SP, Dransfield MT, Cockcroft JR, et al. A randomized trial of once-daily fluticasone furoate/vilanterol or vilanterol versus placebo to determine effects on arterial stiffness in COPD. Int J Chron Obstruct Pulmon Dis. 2017;19(12):351–365. doi:10.2147/COPD.S117373
   Web of Science ®Google Scholar
• Siler TM, Nagai A, Scott-Wilson CA, Midwinter DA, Crim C. A randomised, phase III trial of once-daily fluticasone furoate/vilanterol 100/25 μg versus once-daily vilanterol 25 μg to evaluate the contribution on lung function of fluticasone furoate in the combination in patients with COPD. Respir Med. 2017;123:8–17. doi:10.1016/j.rmed.2016.12.001
   PubMed Web of Science ®Google Scholar
• Ferguson GT, Tashkin DP, Skärby T, et al. Effect of budesonide/formoterol pressurized metered-dose inhaler on exacerbations versus formoterol in chronic obstructive pulmonary disease: the 6-month, randomized RISE (Revealing the Impact of Symbicort in reducing Exacerbations in COPD) study. Respir Med. 2017;132:31–41. doi:10.1016/j.rmed.2017.09.002
   PubMed Web of Science ®Google Scholar
• Ferguson GT, Papi A, Anzueto A. Budesonide/formoterol MDI with co-suspension delivery technology in COPD: the TELOS study. Eur Respir Soc. 2018;52. Available from: https://erj.ersjournals.com/content/52/3/1801334.
   PubMed Web of Science ®Google Scholar
• Rabe KF, Timmer W, Sagkriotis A, Viel K. Comparison of a combination of tiotropium plus formoterol to salmeterol plus fluticasone in moderate COPD. Chest. 2008;134(2):255–262. doi:10.1378/chest.07-2138
   PubMed Web of Science ®Google Scholar
• Magnussen H, Paggiaro P, Schmidt H, Kesten S, Metzdorf N, Maltais F. Effect of combination treatment on lung volumes and exercise endurance time in COPD. Respir Med. 2012;106(10):1413–1420. doi:10.1016/j.rmed.2012.05.011
   PubMed Web of Science ®Google Scholar
• Donohue JF, Worsley S, Zhu C-Q, Hardaker L, Church A. Improvements in lung function with umeclidinium/vilanterol versus fluticasone propionate/salmeterol in patients with moderate-to-severe COPD and infrequent exacerbations. Respir Med. 2015;109(7):870–881. doi:10.1016/j.rmed.2015.04.018
   PubMed Web of Science ®Google Scholar
• Zhong N, Wang C, Zhou X, et al. LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2015;10:1015–1026. doi:10.2147/COPD.S84436
   PubMed Web of Science ®Google Scholar
• Singh D, Worsley S, Zhu C-Q, Hardaker L, Church A. Umeclidinium/vilanterol versus fluticasone propionate/salmeterol in COPD: a randomised trial. BMC Pulm Med. 2015;19(15):91. doi:10.1186/s12890-015-0092-1
   Web of Science ®Google Scholar
• Vogelmeier C, Paggiaro PL, Dorca J, et al. Efficacy and safety of Aclidinium/formoterol versus salmeterol/fluticasone: a phase 3 COPD study. Eur Respir J. 2016;48(4):1030–1039. doi:10.1183/13993003.00216-2016
   PubMed Web of Science ®Google Scholar
• Beeh K-M, Derom E, Echave-Sustaeta J, et al. The lung function profile of once-daily tiotropium and olodaterol via Respimat(®) is superior to that of twice-daily salmeterol and fluticasone propionate via Accuhaler(®) (ENERGITO(®) study). Int J Chron Obstruct Pulmon Dis. 2016;11:193–205. doi:10.2147/COPD.S95055
   PubMed Web of Science ®Google Scholar
• Frith PA, Ashmawi S, Krishnamurthy S, et al. Efficacy and safety of the direct switch to indacaterol/glycopyrronium from salmeterol/fluticasone in non-frequently exacerbating COPD patients: the FLASH randomized controlled trial. Respirology. 2018;23(12):1152–1159. doi:10.1111/resp.13374
   PubMed Web of Science ®Google Scholar
• Greulich T, Kostikas K, Gaga M, et al. Indacaterol/glycopyrronium reduces the risk of clinically important deterioration after direct switch from baseline therapies in patients with moderate COPD: a post hoc analysis of the CRYSTAL study. COPD. 2018;16(13):1229–1237. doi:10.2147/COPD.S159732
   Google Scholar
• A pilot study to assess the effects of combining fluticasone propionate/salmeterol and tiotropium on the airflow obstruction of patients with severe-to-very severe COPD - PubMed [Internet]. [cited December 9, 2021]. Available from: https://pubmed.ncbi.nlm.nih.gov/16914336/. Accessed April 19, 2022.
   Google Scholar
• Bateman ED, van Dyk M, Sagriotis A. Comparable spirometric efficacy of tiotropium compared with salmeterol plus fluticasone in patients with COPD: a pilot study. Pulm Pharmacol Ther. 2008;21(1):20–25. doi:10.1016/j.pupt.2006.10.001
   PubMed Web of Science ®Google Scholar
• Wedzicha JA, Calverley PMA, Seemungal TA, et al. The prevention of chronic obstructive pulmonary disease exacerbations by salmeterol/fluticasone propionate or tiotropium bromide. Am J Respir Crit Care Med. 2008;177(1):19–26. doi:10.1164/rccm.200707-973OC
   PubMed Web of Science ®Google Scholar
• Perng D-W, Tao C-W, Su K-C, Tsai -C-C, Liu L-Y, Lee Y-C. Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD. Eur Respir J. 2009;33(4):778–784. doi:10.1183/09031936.00115308
   PubMed Web of Science ®Google Scholar
• Effects of tiotropium and salmeterol/fluticasone propionate on airway wall thickness in chronic obstructive pulmonary disease - PubMed [Internet]. [cited December 9, 2021]. Available from: https://pubmed.ncbi.nlm.nih.gov/23880883/. Accessed April 19, 2022.
   Google Scholar
• Covelli H, Pek B, Schenkenberger I, Scott-Wilson C, Emmett A, Crim C. Efficacy and safety of fluticasone furoate/vilanterol or tiotropium in subjects with COPD at cardiovascular risk. Int J Chron Obstruct Pulmon Dis. 2015;18(11):1–12. doi:10.2147/COPD.S91407
   Web of Science ®Google Scholar
• Chen H, Sun J, Huang Q, et al. Inhaled corticosteroids and the pneumonia risk in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials. Front Pharmacol. 2021;12:1592.
   Google Scholar
• Paggiaro PL, Vagaggini B, Di Franco A, Zingoni M, Fano M, Biraghi M. Efficacy of nebulized flunisolide combined with salbutamol and ipratropium bromide in stable patients with moderate-to-severe chronic obstructive pulmonary disease. Respiration. 2006;73(5):603–609. doi:10.1159/000089816
   PubMed Web of Science ®Google Scholar
• Magnussen H, Disse B, Rodriguez-Roisin R, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371(14):1285–1294. doi:10.1056/NEJMoa1407154
   PubMed Web of Science ®Google Scholar
• Chapman KR, Hurst JR, Frent S-M, et al. Long-term triple therapy de-escalation to indacaterol/glycopyrronium in patients with chronic obstructive pulmonary disease (SUNSET): a randomized, double-blind, triple-dummy clinical trial. Am J Respir Crit Care Med. 2018;198(3):329–339. doi:10.1164/rccm.201803-0405OC
   PubMed Web of Science ®Google Scholar
• Aaron SD, Vandemheen KL, Fergusson D, et al. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med. 2007;146(8):545–555. doi:10.7326/0003-4819-146-8-200704170-00152
   PubMed Web of Science ®Google Scholar
• Jung KS, Park HY, Park SY, et al. Comparison of tiotropium plus fluticasone propionate/salmeterol with tiotropium in COPD: a randomized controlled study. Respir Med. 2012;106(3):382–389. doi:10.1016/j.rmed.2011.09.004
   PubMed Web of Science ®Google Scholar
• 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. Respir Med. 2012;106(1):91–101. doi:10.1016/j.rmed.2011.09.002
   PubMed Web of Science ®Google Scholar
• Lee S-D, Xie C-M, Yunus F, et al. Efficacy and tolerability of budesonide/formoterol added to tiotropium compared with tiotropium alone in patients with severe or very severe COPD: a randomized, multicentre study in East Asia. Respirology. 2016;21(1):119–127. doi:10.1111/resp.12646
   PubMed Web of Science ®Google Scholar
• Vestbo J, Papi A, Corradi M, et al. Single inhaler extrafine triple therapy versus long-acting muscarinic antagonist therapy for chronic obstructive pulmonary disease (TRINITY): a double-blind, parallel group, randomised controlled trial. Lancet. 2017;389(10082):1919–1929. doi:10.1016/S0140-6736(17)30188-5
   PubMed Web of Science ®Google Scholar
• Janson C. Treatment with inhaled corticosteroids in chronic obstructive pulmonary disease. J Thorac Dis. 2020;12(4):1561–1569. doi:10.21037/jtd.2020.02.51
   PubMed Web of Science ®Google Scholar
• Montuschi P. Pharmacological treatment of chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2006;1(4):409–423. doi:10.2147/copd.2006.1.4.409
   PubMedGoogle Scholar
• Miravitlles M, Soler-Cataluña JJ, Calle M, et al. Spanish guidelines for management of chronic obstructive pulmonary disease (GesEPOC) 2017. Pharmacological treatment of stable phase. Arch Bronconeumol. 2017;53(6):324–335. doi:10.1016/j.arbres.2017.03.018
   PubMed Web of Science ®Google Scholar
• Nici L, Mammen MJ, Charbek E, et al. Pharmacologic management of chronic obstructive pulmonary disease. An official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020;201:e56–e69.
   PubMed Web of Science ®Google Scholar
• Chalmers JD, Laska IF, Franssen FME, et al. Withdrawal of inhaled corticosteroids in COPD: a European Respiratory Society guideline. Eur Respir J. 2020;55(6):2000351. doi:10.1183/13993003.00351-2020
   PubMed Web of Science ®Google Scholar
• Hurst JR. The rhythm of chronic obstructive pulmonary disease exacerbations. J Clin Epidemiol. 2010;63(12):1285–1286. doi:10.1016/j.jclinepi.2010.04.021
   PubMed Web of Science ®Google Scholar
• Soler-Cataluña JJ, Martínez-García MA, Román Sánchez P, Salcedo E, Navarro M, Ochando R. Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax. 2005;60(11):925–931. doi:10.1136/thx.2005.040527
   PubMed Web of Science ®Google Scholar
• Rodrigo GJ, Price D, Anzueto A, et al. LABA/LAMA combinations versus LAMA monotherapy or LABA/ICS in COPD: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2017;12:907.
   PubMed Web of Science ®Google Scholar
• Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD. N Engl J Med. 2020;383(1):35–48. doi:10.1056/NEJMoa1916046
   PubMed Web of Science ®Google Scholar
• Zheng Y, Zhu J, Liu Y, et al. Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis. BMJ. 2018:363. Available from: https://www.bmj.com/content/363/bmj.k4388.
   Google Scholar
• McDonald VM, Fingleton J, Agusti A, et al. Treatable traits: a new paradigm for 21st century management of chronic airway diseases: treatable traits down under international workshop report. Eur Respir J. 2019;53(5):1802058. doi:10.1183/13993003.02058-2018
   PubMed Web of Science ®Google Scholar
• Halpin DMG, Gray J, Edwards SJ, Morais J, Singh D. Budesonide/formoterol vs. salmeterol/fluticasone in COPD: a systematic review and adjusted indirect comparison of pneumonia in randomised controlled trials. Int J Clin Pract. 2011;65(7):764–774. doi:10.1111/j.1742-1241.2011.02685.x
   PubMed Web of Science ®Google Scholar
• Hollis S, Jorup C, Lythgoe D, Martensson G, Regnell P, Eckerwall G. Risk of pneumonia with budesonide-containing treatments in COPD: an individual patient-level pooled analysis of interventional studies. Int J Chron Obstruct Pulmon Dis. 2017;12:1071–1084. doi:10.2147/COPD.S128358
   PubMed Web of Science ®Google Scholar
• Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2014;10(3):CD010115.
   Google Scholar
• Yang M, Du Y, Chen H, Jiang D, Xu Z. Inhaled corticosteroids and risk of pneumonia in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized controlled trials. Int Immunopharmacol. 2019;77:105950. doi:10.1016/j.intimp.2019.105950
   PubMed Web of Science ®Google Scholar