Switching patients from other inhaled corticosteroid devices to the Easyhaler^®: historical, matched-cohort study of real-life asthma patients

Figures & data

Figure 1 Schematic of the study design.

Notes: Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England).
Abbreviations: EH, Easyhaler^®; ICS, inhaled corticosteroid; OH, other inhaler.

Table 1 Matching criteria

Age at IPD
≤16 years	Exact match
≥16 years	±5 years
Sex	Male/female
Year of IPD	±3 years
Most recent ICS scripta	Drug, dosage, and device
Severe exacerbationsb	0, 1, or 2+ in baseline year
SABA usage, average daily dose	0, 1–200, 201–400, 40 1 + μgc in baseline year

Notes:

a Patients were matched on their most recent ICS prescription (drug, dosage, and device) prior to IPD;

b ATS/ERS definition;

c salbutamol-equivalent dosages.

Abbreviations: ATS/ERS, American Thoracic Society/European Respiratory Society; ICS, inhaled corticosteroid; IPD, index prescription date; SABA, short-acting β₂ receptor agonist.

Table 2 Co-primary measures of clinical effectiveness

Outcome	Definition
1. Risk domain asthma control; controlled or uncontrolled	Controlled if: • No asthma-related hospital attendance/admission,a • No GP consultations for LRTI,b and • No prescriptions for acute oral steroid courses
2. Exacerbation rate (ATS/ERS definition); number of exacerbations	Where exacerbation is an occurrence of: • Asthma-related hospital attendance/admissiona or • Use of acute oral steroids
3. Exacerbation rate (clinical definition); number of exacerbations	Where exacerbation is an occurrence of: • Asthma-related hospital attendance/admission,a • GP consult for LRTI,b or • Use of acute oral steroids
4. Overall asthma control; controlled or uncontrolled	Controlled if: • Risk domain asthma control, plus • Average prescribed SABA dosage ≤200 μg/day for salbutamol or ≤500 μg/day for terbutaline

Notes:

a Asthma-related hospital attendance/admission included Accident and Emergency, out-of-hours, and outpatient departments;

b consultations for lower respiratory tract infections requiring antibiotic therapy.

Abbreviations: ATS/ERS, American Thoracic Society/European Respiratory Society; GP, general practitioner; LRTI, lower respiratory tract infection; SABA, short-acting β₂ receptor agonist

Table 3 Secondary measures of clinical effectiveness

Outcome	Definition
Treatment stability (definition 1); stable or unstable	Stable if: • No asthma-related hospital attendance/admission,a • No GP consultations for LRTI,b • No prescriptions for acute oral steroids, and • No change in therapy (≥50% increase in ICS dosage, change in ICS drug or delivery device, and/or additional therapy with theophylline or LTRA)
Treatment stability (definition 2); stable or unstable	Stable if: • No asthma-related hospital attendance/admission,a • No GP consultations for LRTI,b • No prescriptions for acute oral steroids, and • No change in therapy (≥50% increase in ICS dosage and/or additional therapy with theophylline or LTRA)
SABA dosage	Average daily dose (μg)
Controller–reliever ratioc	Categorized: <0.5 or ≥0.5

Notes:

a Asthma-related hospital attendance/admission included Accident and Emergency, out-of-hours, and outpatient departments;

b consultations for lower respiratory tract infections requiring antibiotic therapy;

c calculated as [number of units of controllers/(units of controllers + relievers)].

Abbreviations: GP, general practitioner; ICS, inhaled corticosteroid; LRTI, lower respiratory tract infection; LTRA, leukotriene receptor antagonist; SABA, short-acting β₂ receptor agonist

Table 4 Comparison of co-primary measures of clinical effectiveness between the matched treatment groups during the outcome year

Outcome	EH (n=979)	OH (n=979)	Difference in proportionsa
Risk domain asthma control
Controlled, n (%)	707 (72.2%)	715 (73.0%)	Lower 95% CI:
Adjusted ORb (95% CL)	0.92 (0.74, 1.14)	1.00	−8.7%
Exacerbation rate (ATS/ERS)
0, n (%)	881 (90.0%)	892 (91.1%)	Upper 95% CI:
1, n (%)	78 (8.0%)	71 (7.3%)	4.0%
2+, n (%) P=0.318c	20 (2.0%)	16 (1.6%)
Adjusted RRd (95% CI)	1.18 (0.88, 1.59)	1.00
Exacerbation rate (clinical)
0, n (%)	725 (74.1%)	721 (73.6%)	Upper 95% CI:
1, n (%)	172 (17.6%)	169 (17.3%)	4.0%
2+, n (%) P=0.685c	82 (8.4%)	89 (9.1%)
Adjusted RRe (95% CI)	0.97 (0.82, 1.15)	1.00
Overall asthma control
Controlled, n (%)	401 (41.0%)	356 (36.4%)	Lower 95% CI:
Adjusted ORf (95% CI)	1.26 (1.05, 1.52)	1.00	0.4%

Notes:

a (EH – OH), after adjusting for baseline confounders; non-inferiority is shown if the lower 95% CI is >−10% for asthma control and the upper 95% CI is <10% for exacerbation rate;

b adjusted for baseline rhinitis nasal spray and RDAC, ICS dose at IPD, and age;

c conditional logistic regression;

d adjusted for CCI score and baseline LABA use;

e adjusted for CCI score and baseline exacerbations (clinical);

f adjusted for baseline rhinitis nasal spray and OAC. Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England). The numbers in bold are statistically significant (P<0.05).

Abbreviations: ATS/ERS, American Thoracic Society/European Respiratory Society; CCI, Charlson co-morbidity index; CI, confidence intervals; EH, Easyhaler^®; ICS, inhaled corticosteroid; IPD, index prescription date; LABA, long-acting β₂ receptor agonist; OAC, overall asthma control; OH, other inhalers; OR, odds ratio; RDAC, risk domain asthma control; RR, rate ratio.

Figure 2 Comparison of average daily SABA dosages between baseline and outcome years for the matched treatment groups.

Notes: Patients in both treatment groups were matched on SABA dosage (categorized as shown) during the baseline year, so the baseline values are identical for EH and OH patients; *Using ordinal regression, the number of patients in each dosage category was significantly different (P<0.001) between EH and OH groups during the outcome year. Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England).
Abbreviations: EH, Easyhaler^®; OH, other inhalers; SABA, short-acting β₂ receptor agonist.

Table 5 Comparison of secondary measures of clinical effectiveness between the matched treatment groups during the outcome year

Outcome	EH (n=979)	OH (n=979)	P-valuea
Treatment stability (1)
Stable, n (%)	515 (52.6%)	595 (60.8%)	–
Adjusted ORb (95% CI)	0.67 (0.48, 0.92)	1.00
Treatment stability (2)
Stable, n (%)	589 (60.2%)	636 (65.0%)
Adjusted ORc (95% CI)	0.78 (0.57, 1.06)	1.00
SABA usage (μg/day)
0, n (%)	143 (14.6%)	134 (13.7%)	<0.001d
1–100, n (%)	128 (13.1%)	102 (10.4%)
101–200, n (%)	237 (24.2%)	224 (22.9%)
201–400, n (%)	260 (26.6%)	268 (27.4%)
401–800, n (%)	154 (15.7%)	167 (17.1%)
801+, n (%)	57 (5.8%)	84 (8.6%)
Adjusted ORe (95% CI)	0.69 (0.59, 0.81)	1.00
Controller–reliever ratio
<0.5, n (%)	272 (27.8%)	258 (26.4%)	0.430
≥0.5, n (%)	707 (72.2%)	721 (73.6%)
Mean (SD)	0.6 (0.2)	0.6 (0.2)	0.590
Median (IQR)	0.6 (0.5, 0.8)	0.6 (0.5, 0.8)

Notes:

a Conditional logistic regression, except where noted;

b adjusted for baseline rhinitis nasal spray and exacerbations (clinical);

c adjusted for baseline rhinitis nasal spray and nonasthma-related consultations (categorized);

d ordinal regression;

e odds of EH patients being in a higher SABA category compared with OH patients, adjusted for baseline daily SABA dosage. Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England). The numbers in bold are statistically significant (P<0.05).

Abbreviations: CI, confidence intervals; EH, Easyhaler^®; IQR, interquartile range; OH, other inhalers; OR, odds ratio; SABA, short-acting β₂ receptor agonist; SD, standard deviation.

Table 6 Disaggregated components of the clinical effectiveness measures between the matched treatment groups during the outcome year

Outcome	EH (n=979)	OH (n=979)	P-valuea
Courses of oral steroids
0, n (%)	883 (90.2%)	895 (91.4%)	0.224
1, n (%)	76 (7.8%)	70 (7.2%)
2+, n (%)	20 (2.0%)	14 (1.4%)
SABA dosage (μg/day)
≤200, n (%)	508 (51.9%)	460 (47.0%)	<0.001
>200, n (%)	471 (48.1%)	519 (53.0%)
Increase in ICS dosage
Yes, n (%)	125 (12.8%)	76 (7.8%)	<0.001
Change in ICS drug
Yes, n (%)	171 (17.5%)	94 (9.6%)	<0.001
Change in ICS device
Yes, n (%)	217 (22.2%)	112 (11.4%)	<0.001
Additional therapy
Any, n (%)	113 (11.5%)	96 (9.8%)	0.210
BUD-FOR, n (%)	49 (5.0%)	30 (3.1%)	0.034

Notes:

a Conditional logistic regression. Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England). The numbers in bold are statistically significant (P<0.05).

Abbreviations: BUD-FOR, budesonide-formoterol as fixed-dose combination inhaler; EH, Easyhaler^®; OH, other inhalers; ICS, inhaled corticosteroid; SABA, short-acting β₂ receptor agonist.

Figure 3 Comparison of average daily ICS dosages between baseline and outcome years for the matched treatment groups.

Notes: EH baseline patients were on OH during their baseline year but were switched to EH at IPD; ICS dosages are in BDP-equivalents. in both years, the number of patients in each dosage category was significantly different (P<0.001) between treatment groups (conditional logistic regression). Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England).
Abbreviations: BDP, beclomethasone dipropionate; EH, Easyhaler^®; ICS, inhaled corticosteroid; IPD, index prescription date; OH, other inhalers.

Table 7 Comparison of asthma-related health care costs (£/patient/year) between matched treatment groups for baseline and outcome years, including changes (Δ) in costs from baseline to outcome years

Health economic measure	Baseline			Outcome
	EHa	OH	P-valueb	EH	OH	P-valueb
Total costs (£)
Mean (SD)	165.2 (179.9)	179.2 (231.2)	0.099	192.1 (223.9)	215.4 (268.5)	0.025
Median (IQR)	113.8 (68.8, 198.9)	106.7 (63.3, 208.5)		117.4 (66.1, 223.5)	128.9 (69.2, 251.0)
Δ Total costs (£)
Mean (SD)	–	–	–	26.9 (167.9)	36.2 (158.3)	0.217
Median (IQR)	–	–		2.8 (−46.5, 67.2)	15.7 (−28.2, 72.0)
Asthma drug costs (£)
Mean (SD)	104.6 (159.7)	132.3 (201.0)	<0.001	151.3 (200.5)	179.6 (249.9)	0.003
Median (IQR)	53.6 (25.2, 117.0)	65.3 (32.7, 152.5)		81.9 (44.9, 171.8)	92.9 (45.2, 207.7)
Δ Asthma drug costs (£)
Mean (SD)	–	–	–	46.7 (125.2)	47.2 (123.1)	0.929
Median (IQR)	–	–		20.0 (−3.9, 62.4)	18.6 (−2.8, 61.7)
ICS inhalers (n)
Mean (SD)	4.3 (3.6)	5.5 (4.8)	<0.001	5.5 (3.8)	6.9 (4.7)	<0.001
Median (IQR)	3 (2, 6)	4 (2, 7)		4 (3, 7)	6 (3, 9)
ICS costs (£)
Mean (SD)	50.2 (55.9)	59.3 (75.4)	<0.001	65.0 (51.3)	70.8 (73.0)	0.015
Median (IQR)	30.9 (14.8, 65.9)	38.9 (17.2, 76.2)		50.3 (29.9, 88.6)	49.0 (23.7, 89.6)
Δ ICS costs (£)
Mean (SD)	–	–	–	14.7 (46.1)	11.4 (40.3)	0.094
Median (IQR)	–	–		14.0 (−2.9, 34.7)	7.9 (−1.2, 27.5)
SABA inhalers (n)	–	–
Mean (SD)	4.8 (6.8)	4.9 (7.2)	0.347	5.1 (6.9)	6.0 (7.8)	0.001
Median (IQR)	3 (1, 6)	3 (1, 6)		3 (1, 7)	4 (2, 8)
SABA costs (£)
Mean (SD)	18.7 (34.7)	18.5 (33.6)	0.863	21.0 (43.5)	26.3 (59.2)	0.024
Median (IQR)	9.2 (2.9, 22.7)	9.0 (2.9, 23.0)		11.8 (3.3, 23.2)	11.5 (4.6, 28.8)
Δ SABA costs (£)
Mean (SD)	–	–	–	2.3 (25.7)	7.8 (40.5)	0.001
Median (IQR)	–	–		0.4 (−3.3, 7.1)	1.5 (−2.3, 8.6)
Asthma consultsc (n)
Mean (SD)	1.4 (1.2)	1.0 (1.0)	<0.001	0.9 (1.2)	0.9 (1.0)	0.658
Median (IQR)	1 (1, 2)	1 (0, 1)		1 (0, 1)	1 (0, 1)
Consult costs (£)
Mean (SD)	50.3 (43.8)	36.1 (36.7)	<0.001	31.6 (41.3)	30.8 (36.7)	0.658
Median (IQR)	36 (36, 72)	36 (0, 36)		36 (0, 36)	36 (0, 36)
Δ Consult costs (£)
Mean (SD)	–	–	–	−18.8 (54.3)	−5.3 (44.0)	<0.001
Median (IQR)	–	–		−36 (−36, 0)	0 (−36, 0)
Hospitalizationsd (n)
Mean (SD)	0.06 (0.28)	0.02 (0.19)	0.001	0.05 (0.29)	0.02 (0.19)	0.004
Median (IQR)	0 (0, 0)	0 (0, 0)		0 (0, 0)	0 (0, 0)
Hospital costs (£)
Mean (SD)	7.5 (38.4)	2.3 (26.2)	0.001	7.3 (38.6)	2.8 (25.0)	0.004
Median (IQR)	0 (0, 0)	0 (0, 0)		0 (0, 0)	0 (0, 0)
Δ Hospital costs (£)
Mean (SD)	–	–	–	−0.14 (48.3)	0.41 (33.2)	0.767
Median (IQR)	–	–		0 (0, 0)	0 (0, 0)

Notes:

a These patients were on OH during their baseline year but were switched to EH at IPD;

b conditional logistic regression;

c asthma-related primary-care consultations;

d asthma-related hospital outpatient department attendance. Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England). The numbers in bold are statistically significant (P<0.05).

Abbreviations: Δ, change; EH, Easyhaler^®; ICS, inhaled corticosteroid; IPD, index prescription date; IQR, interquartile range; OH, other inhalers; OPD, outpatient department; SABA, short-acting β₂ receptor agonist; SD, standard deviation.

Figure S1 Potential confounders examined in the initial analysis.

Notes: ^aThe equations of Roberts et al¹ were used for patients >18 years of age and the equations of Rosenthal et al² were used for patients 6–18 years of age; ^bas described by Aylin et al.³

Table S1 Baseline patient characteristics: demographics and co-morbidities

Variable	EHa (n=979)b	OH (n=979)b	P-valuec
Age at IPD (years)
Mean (SD)	40.5 (25.9)	40.5 (25.9)	0.708
Median (IQR)	41 (13, 64)	41 (13, 64)
Categorized			N/Ad
Pediatric (6–11 years), n (%)	190 (19.4%)	190 (19.4%)
Adult (12–60 years), n (%)	498 (50.9%)	498 (50.9%)
Elderly (61–80 years), n (%)	291 (29.7%)	291 (29.7%)
Sex			N/Ad
Male, n (%)	439 (44.8%)	439 (44.8%)
Female, n (%)	540 (55.2%)	540 (55.2%)
Smoking status			0.563
Nonsmoker, n (%)	610 (62.3%)	604 (61.7%)
Current smoker, n (%)	127 (13.0%)	138 (14.1%)
Ex-smoker, n (%)	196 (20.0%)	195 (19.9%)
Unknown, n (%)	46 (4.7%)	42 (4.3%)
% Predicted PEFe
Mean (SD)	84.3 (22.6)	84.3 (24.9)	0.937
Median (IQR)	85.5 (68.7, 99.1)	83.9 (66.6, 100.8)
Patients, n	545	590
Year of IPD
Mean (SD)	2007.9 (1.7)	2007.9 (1.5)	N/Ad
Median (IQR)	2008 (2007, 2009)	2008 (2007, 2009)
CCI score			<0.001
0	475 (48.5%)	578 (59.0%)
1–4	401 (41.0%)	313 (32.0%)
5+	103 (10.5%)	88 (9.0%)
Co-morbidities
Rhinitis,f n (%)	237 (24.2%)	296 (30.2%)	0.003

Notes:

a These patients were on OH during their baseline year but were switched to EH at IPD;

b except where noted;

c conditional logistic regression;

d matching variable;

e see Figure S1 for age-specific PEF equations used;

f rhinitis diagnosis and/or prescription for rhinitis drugs. Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England).

Abbreviations: CCI, Charlson co-morbidity index; EH, Easyhaler^®; IPD, index prescription date; IQR, interquartile range; N/A, not applicable; OH, other inhalers; PEF, peak expiratory flow; SD, standard deviation.

Table S2 Baseline patient characteristics: disease severity and therapies

Variable	EHa (n=979)	OH (n=979)	P-valueb
Risk domain asthma control
Controlled, n (%)	645 (65.9%)	656 (67.0%)	0.534
Exacerbation rate (ATS/ERS)
Mean (SD)	0.14 (0.45)	0.14 (0.42)	0.370
Median (IQR)	0 (0, 0)	0 (0, 0)
Categorized			N/Ac
0, n (%)	865 (88.4%)	865 (88.4%)
1, n (%)	99 (10.1%)	99 (10.1%)
2+, n (%)	15 (1.5%)	15 (1.5%)
Exacerbation rate (clinical)
Mean (SD)	0.47 (0.85)	0.47 (0.84)	0.899
Median (IQR)	0 (0, 1)	0 (0, 1)
Categorized			0.713
0, n (%)	672 (68.6%)	660 (67.4%)
1, n (%)	213 (21.8%)	228 (23.3%)
2+, n (%)	94 (9.6%)	91 (9.3%)
Overall asthma control
Controlled, n (%)	597 (61.0%)	591 (60.4%)	0.655
Acute oral steroid courses
Mean (SD)	0.13 (0.43)	0.12 (0.39)	0.253
Median (IQR	0 (0, 0)	0 (0, 0)
Categorized			0.334
0, n (%)	878 (89.7%)	884 (90.3%)
1, n (%)	87 (8.9%)	81 (8.3%)
2+, n (%)	14 (1.4%)	14 (1.4%)
LRTI consults with a/b script
Mean (SD)	0.43 (0.86)	0.44 (0.88)	0.870
Median (IQR)	0 (0, 1)	0 (0, 1)
Categorized			0.796
0, n (%)	709 (72.4%)	697 (71.2%)
1+, n (%)	270 (27.6%)	282 (28.8%)
Primary-care consultations
Mean (SD)
All consults	8.8 (7.1)	8.8 (7.9)	0.995
Asthma-related	1.4 (1.2)	1.0 (1.0)	<0.001
Asthma, no oral steroids	1.3 (1.1)	0.9 (1.0)	<0.001
Respiratory prescriptions
Mean (SD)
All scripts	9.1 (9.2)	10.3 (8.9)	<0.001
Allergy scripts	1.7 (3.6)	2.2 (4.6)	0.005
SABA scripts	3.7 (4.3)	3.7 (4.4)	0.944
ICS scripts	3.8 (3.2)	4.6 (3.3)	<0.001
ICS inhalers	4.3 (3.6)	5.5 (4.8)	<0.001
Average daily SABA dose (μg)d
Mean (SD)	270.6 (395.8)	277.9 (420.9)	0.549
Median (IQR)	164.4 (54.8, 328.8)	164.4 (54.8, 328.8)
Categorized			N/Ac
0, n (%)	165 (16.9%)	165 (16.9%)
1–200, n (%)	395 (40.3%)	395 (40.3%)
201–400, n (%)	218 (22.3%)	218 (22.3%)
401+, n (%)	201 (20.5%)	201 (20.5%)
LABA use
Yes, n (%)	81 (8.3%)	150 (15.3%)	<0.001
Average daily ICS dose (μg)e
Mean (SD)	309.9 (334.7)	384.3 (440.2)	<0.001
Median (IQR)	197.3 (109.6, 394.5)	263.0 (109.6, 438.4)
Categorized			<0.001
1–100, n (%)	192 (19.6%)	148 (15.1%)
101–200, n (%)	303 (30.9%)	234 (23.9%)
201–400, n (%)	241 (24.6%)	302 (30.8%)
401+, n (%)	243 (24.8%)	295 (30.1%)
Asthma-related hospitalizationf
A&E attendance, n (%)	3 (0.3%)	4 (0.4%)	0.708
Inpatient admission, n (%)	3 (0.3%)	8 (0.8%)	0.148
Inpatient (incl vague), n (%)	25 (2.6%)	20 (2.0%)	0.447
Outpatient attendance, n (%)	43 (4.4%)	13 (1.3%)	<0.001
Controller–reliever ratio
Mean (SD)	0.6 (0.3)	0.6 (0.2)	<0.001
Median (IQR)	0.5 (0.4, 0.7)	0.5 (0.5, 08)
Categorized			<0.001
<0.5, n (%)	349 (35.6%)	262 (26.8%)
≥0.5, n (%)	630 (64.4%)	717 (73.2%)

Notes:

a These patients were on OH during their baseline year but were switched to EH at IPD;

b conditional logistic regression;

c matching variable;

d salbutamol-equivalent dosages;

e BDP-equivalent dosages; average daily ICS dosage = total combined dose of re/filled prescriptions, averaged over 365 days;

f any asthma- or respiratory-related hospital attendance/admission during the baseline year. Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England). The numbers in bold are statistically significant (P<0.05).

Abbreviations: a/b, antibiotic; A&E, Accident and Emergency department; ATS/ERS, American Thoracic Society/European Respiratory Society; BDP, beclomethasone dipropionate; EH, Easyhaler^®; ICS, inhaled corticosteroid; IPD, index prescription date; IQR, interquartile range; LABA, long-acting β₂ receptor agonist; LRTI, lower respiratory tract infection; N/A, not applicable; OH, other inhalers; SABA, short-acting β₂ receptor agonist; SD, standard deviation.

Table S3 Baseline patient characteristics: ICS drugs, dosages, and devices

Variable	EHa (n=979)	OH (n=979)	P-valueb
ICS drug prior to IPD			N/Ac
Beclomethasone, n (%)	827 (84.5%)	827 (84.5%)
Fluticasone, n (%)	22 (2.2%)	22 (2.2%)
Budesonide, n (%)	129 (13.2%)	129 (13.2%)
Ciclesonide, n (%)	1 (0.1%)	1 (0.1%)
ICS drug at IPD			<0.001
Beclomethasone, n (%)	525 (53.6%)	827 (84.5%)
Fluticasone, n (%)	0 (0.0%)	22 (2.2%)
Budesonide, n (%)	454 (46.4%)	129 (13.2%)
Ciclesonide, n (%)	0 (0.0%)	1 (0.1%)
ICS dosage prior to IPD (μg)d
Mean (SD)	467.0 (238.8)	467.0 (238.8)	N/Ac
Median (IQR)	400 (400, 400)	400 (400, 400)
Categorized			N/Ac
1–200, n (%)	188 (19.2%)	188 (19.2%)
201–400, n (%)	561 (57.3%)	561 (57.3%)
401+, n (%)	230 (23.5%)	230 (23.5%)
ICS dosage at IPD (μg)d
Mean (SD)	368.9 (162.2)	466.2 (243.0)	<0.001
Median (IQR)	400 (200, 400)	400 (400, 400)
Categorized			<0.001
1–200, n (%)	310 (31.7%)	189 (19.3%)
201–400, n (%)	592 (60.5%)	564 (57.6%)
401+, n (%)	77 (7.9%)	226 (23.1%)
ICS device prior to IPD			N/Ac
MDI, n (%)	610 (62.3%)	610 (62.3%)
BAI, n (%)	182 (18.6%)	182 (18.6%)
DPI, n (%)	187 (19.1%)	187 (19.1%)
ICS device at IPD			0.984
MDI, n (%)	0 (0.0%)	610 (62.3%)
BAI, n (%)	0 (0.0%)	182 (18.6%)
DPI, n (%)	979 (100.0%)	187 (19.1%)

Notes:

a These patients were on OH during their baseline year but were switched to EH at IPD;

b conditional logistic regression;

c matching variable;

d BDP-equivalents. Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England). The numbers in bold are statistically significant (P<0.05).

Abbreviations: BAI, breath-actuated inhaler; BDP, beclomethasone dipropionate; DPI, dry-powder inhaler; EH, Easyhaler^®; ICS, inhaled corticosteroid; IPD, index prescription date; IQR, interquartile range; MDI, metered-dose inhaler; N/A, not applicable; OH, other inhalers; SD, standard deviation.

Table S4 Patient characteristics during the outcome year: disease severity and therapies

Variable	EHa (n=979)	OH (n=979)	P-valueb
Risk domain asthma control
Controlled, n (%)	707 (72.2%)	715 (73.0%)	0.677
Exacerbation rate (ATS/ERS)
Mean (SD)	0.13 (0.45)	0.11 (0.42)	0.337
Median (IQR)	0 (0, 0)	0 (0, 0)
Categorized			0.318
0, n (%)	881 (90.0%)	892 (91.1%)
1, n (%)	78 (8.0%)	71 (7.3%)
2+, n (%)	20 (2.0%)	16 (1.6%)
Exacerbation rate (clinical)
Mean (SD)	0.4 (0.9)	0.4 (0.9)	0.866
Median (IQR)	0 (0, 1)	0 (0, 1)
Categorized			0.685
0, n (%)	725 (74.1%)	721 (73.6%)
1, n (%)	172 (17.6%)	169 (17.3%)
2+, n (%)	82 (8.4%)	89 (9.1%)
Overall asthma control
Controlled, n (%)	401 (41.0%)	356 (36.4%)	0.016
Acute oral steroid courses
Mean (SD)	0.13 (0.44)	0.11 (0.40)	0.216
Median (IQR)	0 (0, 0)	0 (0, 0)
Categorized			0.224
0, n (%)	883 (90.2%)	895 (91.4%)
1, n (%)	76 (7.8%)	70 (7.2%)
2+, n (%)	20 (2.0%)	14 (1.4%)
LRTI consults with a/b script
Mean (SD)	0.39 (0.87)	0.39 (0.86)	0.978
Median (IQR)	0 (0, 0)	0 (0, 0)
Categorized			0.745
0, n (%)	742 (75.8%)	748 (76.4%)
1+, n (%)	237 (24.2%)	231 (23.6%)
Primary-care consultations
Mean (SD)
All consults	8.8 (8.1)	8.9 (8.7)	0.659
Asthma-related	0.9 (1.1)	0.9 (1.0)	0.658
Asthma, no oral steroids	0.8 (1.1)	0.8 (0.9)	0.784
Respiratory prescriptions
Mean (SD)
All scripts	10.8 (9.9)	12.6 (10.1)	<0.001
Allergy scripts	1.9 (4.4)	2.5 (4.7)	0.006
SABA scripts	4.1 (4.5)	4.5 (4.8)	0.012
ICS scripts	4.8 (3.4)	5.8 (3.6)	<0.001
ICS inhalers	5.5 (3.8)	6.9 (4.7)	<0.001
Average daily SABA dose (μg)c
Mean (SD)	281.3 (390.9)	332.7 (441.9)	<0.001
Median (IQR)	164.4 (54.8, 383.6)	219.2 (109.6, 438.4)
Categorized			<0.001
0, n (%)	143 (14.6%)	134 (13.7%)
1–200, n (%)	365 (37.3%)	326 (33.3%)
201–400, n (%)	260 (26.6%)	268 (27.4%)
401+, n (%)	211 (21.5%)	251 (25.6%)
LABA use
Yes, n (%)	101 (10.3%)	160 (16.3%)	<0.001
Average daily ICS dose (μg)d
Mean (SD)	355.1 (304.8)	493.6 (462.1)	<0.001
Median (IQR)	274 (164, 438)	329 (192, 658)
Categorized			<0.001
1–200, n (%)	327 (33.4%)	249 (25.4%)
201–400, n (%)	375 (38.3%)	315 (32.2%)
401–800, n (%)	202 (20.6%)	235 (24.0%)
801+, n (%)	75 (7.7%)	180 (18.4%)
Asthma-related hospitalizatione
A&E attendance, n (%)	2 (0.2%)	5 (0.5%)	0.274
Inpatient admission, n (%)	2 (0.2%)	2 (0.2%)	1.000
Inpatient (incl vague), n (%)	16 (1.6%)	12 (1.2%)	0.451
Outpatient attendance, n (%)	41 (4.2%)	14 (1.4%)	<0.001
Controller–reliever ratio
Mean (SD)	0.6 (0.2)	0.6 (0.2)	0.590
Median (IQR)	0.5 (0.5, 0.8)	0.5 (0.5, 08)
Categorized			0.430
<0.5, n (%)	272 (27.8%)	258 (26.4%)
≥0.5, n (%)	707 (72.2%)	721 (73.6%)

Notes:

a These patients were on OH during their baseline year but were switched to EH at IPD;

b conditional logistic regression;

c salbutamol-equivalent dosages;

d BDP-equivalent dosages;

e any asthma- or respiratory-related hospital attendance/admission during the baseline year. Easyhaler^® (Orion Pharma UK Ltd, Newbury, Berkshire, England). The numbers in bold are statistically significant (P<0.05).

Abbreviations: a/b, antibiotic; A&E, Accident and Emergency department; ATS/ERS, American Thoracic Society/European Respiratory Society; BDP, beclomethasone dipropionate; EH, Easyhaler^®; ICS, inhaled corticosteroid; IPD, index prescription date; IQR, interquartile range; LABA, long-acting β₂ receptor agonist; LRTI, lower respiratory tract infection; N/A, not applicable; OH, other inhalers; SABA, short-acting β₂ receptor agonist; SD, standard deviation.

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