High versus Medium Dose of Inhaled Corticosteroid in Chronic Obstructive Lung Disease: A Systematic Review and Meta-Analysis

Figures & data

Figure 1 PRISMA Flowchart.

Table 1 Baseline Characteristics of Study Populations in the Included RCTs

Study	(N of Males)	Follow-up Time	High Dose ICS	Medium Dose ICS	Ancillary Medication	Age High/ Medium Dose *	PY High/ Medium Dose *	Mean FEV1 High/ Medium Dose	N with GOLD 2–4 High/ Medium Dose	N with recent M/S AE High/ Medium Dose
Cheng et al, 2014^Citation20	106(92)/ 111(93)	52 weeks	Fluticasone Propionate 1000µg/day	Fluticasone Propionate 500µg/day	Salmeterol	66.4±20.3/ 68±23.4	27.4±16.5/29.1±19.3	1.24/1.27	29-47-30/24-51-36	NA/NA
Doherty et al, 2012^Citation21	225(168)/239(175)	52 weeks	Mometasone 800µg/day	Mometasone 400µg/day	Formoterol	59.2±9.1/ 60.1±9.0/	54.8±186.4/40.3±26.2	NA/NA	NA/NA	NA/NA
Dransfield et al, 2013^Citation22	402(249), 409(218)/403(231), 403(222)	52 weeks	Fluticasone Furoate 200 µg/day	Fluticasone Furoate 100 µg/day	Vilanterol	63.8±9.3, 63.5±8.8/ 63.6±9.1, 64.0±9.3	NA/NA	1.3–1.3/1.3–1.3	NA/NA	402–409/403–403
Ferguson et al, 2018^Citation23	655(402)/637(377)	24 weeks	Budesonide 640µg/day	Budesonide 320µg/day	Formoterol	64.2±7.7/64.3±7.6/	44.7±23.5/ 44.7±22.1	1.548/1.532	NA/NA	168/188
Hanania et al, 2020^Citation24	619(367)/617(345)	12 to 52 weeks	Budesonide 640µg/day	Budesonide 320µg/day	Formoterol	65.3±8.1/64.5±8.4/	44.2±26.0/45.8±28.0	NA/NA	338-241-37/330-230-56	614/616
Martinez et al, 2013^Citation25	205(137)/204(144)	24 weeks	Fluticasone Furoate 200 µg/day	Fluticasone Furoate 100 µg/day	Vilanterol	61.1±8.6/61.9±8.8/	41.5±23.4/42.8±23.9	1.458/1.491	NA/NA	53/50
Papi et al, 2017^Citation26	587(443)/588(427)	52 weeks	Fluticasone Propionate 1000µg/day	Fluticasone Propionate 500µg/day	Formoterol	63.8±7.9/63.0±7.8/	39.1±19.5/39.2±20.1	1.03/1.02	NA/NA	NA/NA
Rabe et al, 2020^Citation13	2137(1260)/ 2121(1298)	52 weeks	Budesonide 640µg/day	Budesonide 320µg/day	Glycopyrrolate and Formoterol	64.6±7.6/64.6±7.6/	47.0±25.1/47.9±25.8	NA/NA	NA/NA	2135/ 2119
Rennard et al, 2009^Citation27	494(308)/494(310)	12 months	Budesonide 640µg/day	Budesonide 320µg/day	Formoterol	63.2±8.9/63.6±9.2/	40**/40**	1.00/1.00	84-290-120/85-314-94	NA/NA
Sharafkhaneh et al, 2012^Citation28	407(262)/408(264)	12 months	Budesonide 640µg/day	Budesonide 320µg/day	Formoterol	63.8±9.4/62.8±9.2/	46**/44**	1.01/1.02	NA/NA	163/165
Tashkin et al, 2008^Citation30	277(188)/281(181)	6 months	Budesonide 640µg/day	Budesonide 320µg/day	Formoterol	63.1±9.0/63.6±9.0/	40**/40**	1.04/1.04	NA/NA	NA/NA
Tashkin et al, 2012^Citation29	217(171)/207(161)	52 weeks	Mometasone 800µg/day	Mometasone 400µg/day	Formoterol	59.7±9.1/60.9±8.1/	39.7±28.4/41.7±43.4	NA/NA	NA/NA	NA/NA
Zheng et al, 2015^Citation31	160(145)/161(144)	24 weeks	Fluticasone Furoate 200 µg/day	Fluticasone Furoate 100 µg/day	Vilanterol	62.7±8.7/65.1±9.2/	37.4±22.2/39.0±22.2	1.064/1.096	NA/NA	41/42

Notes: *Data presented in Mean±SD form, **Number represents Median instead of Mean.

Abbreviations: N, Number; PY, Pack Year History; NA, Not available.

Figure 2 Comparison of Any AECOPD Risk between patients with COPD using High Dose ICS versus Medium ICS as part of maintenance therapy.

Figure 3 Comparison of Mortality Risk Rate between patients with COPD using High Dose ICS versus Medium ICS as part of maintenance therapy.

Figure 4 Comparison of Moderate/Severe AECOPD Risk between patients with COPD using High Dose ICS versus Medium ICS as part of maintenance therapy.

Figure 5 Comparison of Pneumonia risk between patients with COPD using High Dose ICS versus Medium ICS as part of maintenance therapy.

Cheng SL, Su KC, Wang HC, Perng DW, Yang PC. Chronic obstructive pulmonary disease treated with inhaled medium- or high-dose corticosteroids: a prospective and randomized study focusing on clinical efficacy and the risk of pneumonia. Drug Des Devel Ther. 2014;8:601–607. doi:10.2147/DDDT.S63100

 PubMed Web of Science ®Google Scholar

Doherty DE, Tashkin DP, Kerwin E, et al. Effects of mometasone furoate/formoterol fumarate fixed-dose combination formulation on chronic obstructive pulmonary disease (COPD): results from a 52-week Phase III trial in subjects with moderate-to-very severe COPD. Int J Chron Obstruct Pulmon Dis. 2012;7:57–71. doi:10.2147/COPD.S27320

 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

Ferguson GT, Papi A, Anzueto A, et al. Budesonide/formoterol MDI with co-suspension delivery technology in COPD: the TELOS study. Eur Respir J. 2018;52(3):1801334. doi:10.1183/13993003.01334-2018

 PubMed Web of Science ®Google Scholar

Hanania NA, Papi A, Anzueto A, et al. Efficacy and safety of two doses of budesonide/formoterol fumarate metered dose inhaler in COPD. ERJ Open Res. 2020;6:2. doi:10.1183/23120541.00187-2019

 Google Scholar

Martinez FJ, Boscia J, Feldman G, et al. Fluticasone furoate/vilanterol (100/25; 200/25 mug) 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

Papi A, Dokic D, Tzimas W, et al. Fluticasone propionate/formoterol for COPD management: a randomized controlled trial. Int J Chron Obstruct Pulmon Dis. 2017;12:1961–1971. doi:10.2147/COPD.S136527

 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

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: results from a 1-year randomized controlled clinical trial. Drugs. 2009;69(5):549–565. doi:10.2165/00003495-200969050-00004

 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

Tashkin DP, Rennard SI, Martin P, et al. Efficacy and safety of budesonide and formoterol in one pressurized metered-dose inhaler in patients with moderate to very severe chronic obstructive pulmonary disease: results of a 6-month randomized clinical trial. Drugs. 2008;68(14):1975–2000. doi:10.2165/00003495-200868140-00004

 PubMed Web of Science ®Google Scholar

Tashkin DP, Doherty DE, Kerwin E, et al. Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial. Int J Chron Obstruct Pulmon Dis. 2012;7:43–55. doi:10.2147/COPD.S27319

 PubMed Web of Science ®Google Scholar

Zheng J, de Guia T, Wang-Jairaj J, et al. Efficacy and safety of fluticasone furoate/vilanterol (50/25 mcg; 100/25 mcg; 200/25 mcg) in Asian patients with chronic obstructive pulmonary disease: a randomized placebo-controlled trial. Curr Med Res Opin. 2015;31(6):1191–1200. doi:10.1185/03007995.2015.1036016

 PubMed Web of Science ®Google Scholar