The comparative effectiveness of initiating fluticasone/salmeterol combination therapy via pMDI versus DPI in reducing exacerbations and treatment escalation in COPD: a UK database study

Figures & data

Table 1 Selected matching criteria

Criteria	Categories
Sex	Male/female
Age at initiation with FP/SAL	±5 years
Baseline COPD exacerbations	0, 1, 2, 3+
Number of baseline LAMA prescriptions	0, 1, 2+
Baseline lower respiratory tract infections	0, 1, 2, 3+
Diabetes diagnosis at or prior to initiation with FP/SAL	Diabetes with no insulin/diabetes and insulin/no diabetes

Abbreviations: COPD, chronic obstructive pulmonary disease; FP/SAL, fluticasone propionate/salmeterol xinafoate; LAMA, long-acting muscarinic agonist.

Table 2 Baseline patient characteristics

Characteristic	FP/SAL 500 μg/d			FP/SAL 1,000 μg/d
	pMDI (n=236)	DPI (n=236)	P-valuea	pMDI (n=586)	DPI (n=586)	P-valuea
Sexb, n (%) male	136 (58)	136 (58)	N/A	355 (61)	355 (61)	N/A
Ageb (years), median (IQR)	68 (61, 75)	67 (61, 75)	0.319	69 (62, 75)	69 (63, 75)	0.959
Year of first prescription of FP/SAL, median (IQR)	2006 (2004, 2008)	2006 (2004, 2008)	0.013	2007 (2005, 2009)	2009 (2006, 2010)	<0.001
Smoking status, n (%)
Non	29 (12)	34 (14)	0.238	40 (7)	42 (7)	0.940
Current	104 (44)	87 (37)		252 (43)	251 (43)
Ex	102 (43)	115 (49)		293 (50)	292 (50)
GOLD group,c n (%)
A	65 (33)	72 (37)	0.915	141 (29)	147 (28)	0.901
B	48 (25)	46 (24)		118 (24)	123 (23)
C	39 (20)	42 (21)		114 (23)	113 (22)
D	43 (22)	36 (18)		119 (24)	143 (27)
Moderate/severe COPD exacerbations,b n (%)
0	123 (52)	129 (55)	0.368	299 (51)	302 (52)	0.207
1	62 (26)	60 (25)		174 (30)	164 (28)
2–3	48 (20)	41 (17)		91 (16)	100 (17)
≥4	3 (1)	6 (3)		22 (4)	20 (3)
LAMA prescription,b n (%)	17 (7)	17 (7)	N/A	151 (26)	151 (26)	N/A
Diabetes mellitus,b,d n (%)	35 (15)	35 (15)	N/A	115 (20)	115 (20)	N/A
Asthma,d n (%)	30 (13)	44 (19)	0.069	50 (9)	61 (10)	0.265
Ischemic heart disease,d n (%)	46 (20)	44 (19)	0.811	136 (23)	111 (19)	0.077
Chronic kidney disease,d n (%)	7 (3)	19 (8)	0.024	30 (5)	39 (7)	0.251

Notes:

a Conditional logistic regression;

b Matching criteria;

c Reference 52;

d Identified by diagnostic read codes recorded at or prior to initiation with FP/SAL, diabetes mellitus includes antidiabetic drug prescriptions, asthma excludes resolved cases, chronic kidney disease includes patients in stages 3–5 and all those with evidence of proteinuria.

Abbreviations: COPD, chronic obstructive pulmonary disease; DPI, dry powdered inhaler; FP/SAL, fluticasone propionate/salmeterol xinafoate; GOLD, Global Initiative for Chronic Obstructive Lung Disease; IQR, interquartile range; LAMA, long-acting muscarinic agonist; N/A, not applicable; pMDI, pressurized metered-dose inhaler.

Table 3 Moderate/severe COPD, LAMA prescription, pneumonia, and diabetes mellitus during the outcome year

Characteristic	FP/SAL 500 μg/d			FP/SAL 1,000 μg/d
	pMDI (N=236)	DPI (N=236)	P-value (CLR)	pMDI (N=586)	DPI (N=586)	P-value (CLR)
Moderate/severe COPD exacerbations, n (%)
0	137 (58)	121 (51)		299 (51)	317 (54)
1	56 (24)	59 (25)	0.032	152 (26)	149 (25)	0.245
2–3	35 (15)	35 (15)		100 (17)	87 (15)
≥4	8 (3)	21 (9)		35 (6)	33 (6)
LAMA prescription, n (%)	51 (22)	59 (25)	0.319	252 (43)	291 (50)	0.008
Pneumonia, n (%)	5 (2)	4 (2)	0.739	4 (1)	3 (1)	0.706
Diabetes mellitus,a n (%)	8 (4)	6 (3)	0.594	27 (6)	26 (6)	0.889

Note:

a As a percentage of patients without diabetes mellitus prior to first prescription of FP/SAL.

Abbreviations: CLR, conditional logistic regression; COPD, chronic obstructive pulmonary disease; DPI, dry powdered inhaler; FP/SAL, fluticasone propionate/salmeterol xinafoate; LAMA, long-acting muscarinic agonist; pMDI, pressurized metered-dose inhaler.

Figure 1 Comparison of outcomes between pMDI and DPI, in the 500 μg/d cohort.

Notes: *RR adjusted for number of baseline moderate/severe COPD exacerbations; ^†OR adjusted for baseline LAMA prescription (yes/no); ^‡unadjusted OR. Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; LAMA, long-acting muscarinic agonists; MDI, metered-dose inhaler; OR, odds ratio; pMDI, pressurized metered-dose inhaler; RR, rate ratio.

Figure 2 Comparison of outcomes between pMDI and DPI, in the 1,000 μg/d cohort.

Notes: *RR adjusted for number of baseline moderate/severe COPD exacerbations; ^†OR adjusted for baseline LAMA prescription (yes/no); ^‡unadjusted OR.
Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; LAMA, long-acting muscarinic agonists; MDI, metered-dose inhaler; OR, odds ratio; pMDI, pressurized metered-dose inhaler; RR, rate ratio.

Figure S1 Patient flow diagram.

Abbreviations: COPD, chronic obstructive pulmonary disease; DPI, dry powdered inhaler; FEV₁, forced expiratory volume in 1 second; FP/SAL, fluticasone propionate/salmeterol xinafoate; FVC, forced vital capacity; ICS, inhaled corticosteroids; OPCRD, Optimum Patient Care Research Database; pMDI, pressurized metered-dose inhaler.