Non-adherence to inhaled corticosteroids and the risk of asthma exacerbations in children

Figures & data

Figure 1 Flowchart for patient selection.

Abbreviations: PHARMO RLS, PHARMO Record Linkage System; ICS, inhaled corticosteroid.

Table 1 Characteristics of analyzed patient moments

Variable	Categories/details	Event moments (with asthma exacerbation) (n=40)	Control moments (without exacerbation) (n=1,596)	P-valuea
Type of ICS, N (%)	Fluticasone	30 (75.0)	1,127 (70.6)	0.613
	Beclomethasone	3 (7.5)	283 (17.7)
	Budesonide	7 (17.5)	186 (11.6)
ICS dose, mean (SD)	Proportion of the defined daily dose	0.60 (0.36)	0.57 (0.67)	0.650
Dosing frequency ICS, N (%)	1 time a day	1 (2.5)	78 (4.9)	0.497
	1–2 times a day	0 (0.0)	16 (1.0)
	2 times a day	38 (95.0)	1,440 (91.3)
	2–3 times	0 (0.0)	2 (0.1)
	3 times a day	1 (2.5)	36 (2.3)
	4 times a day	0 (0.0)	5 (0.3)
Time from cohort entry to index date, mean (SD)	Years	1.87 (1.41)	1.80 (1.29)	0.184
Type of inhaler, N (%)	pMDI	23 (57.5)	878 (55.0)	0.938
	Extrafine particle pMDI	1 (2.5)	31 (1.9)
	DPI	16 (40.0)	687 (43.0)
Prescriber, N (%)	General practitioner	28 (70.0)	1,310 (82.1)	0.134
	Pediatrician	10 (25.0)	238 (14.9)
	Pulmonologist	2 (5.0)	33 (2.1)
	Other	0 (0.0)	15 (0.9)
SABA, number of Rx preceding the index date, mean (SD)	SABA 12 months	2.9 (2.0)	1.8 (2.0)	0.002
	SABA 3 months	1.3 (1.4)	0.6 (1.0)	0.001
LABA, number of Rx preceding the index date, mean (SD)	LABA 12 months	1.5 (2.5)	0.8 (1.8)	0.004
	LABA 3 months	0.6 (1.0)	0.3 (0.8)	0.013
Combined LABA and ICS, number of Rx preceding the index date, mean (SD)	LABA + ICS 12 months	1.3 (2.3)	0.7 (1.7)	0.015
	LABA + ICS 3 months	0.5 (0.9)	0.3 (0.7)	0.030
SAMA, patient moments with ≥1 Rx preceding the index date, N (%)	SAMA 12 months	2 (5)	12 (0.8)	NAb
	SAMA 3 months	2 (5)	4 (0.3)
Leukotriene antagonists, patient moments with ≥1 Rx preceding the index date, N (%)	Montelukast	3 (7.5)	69 (4.3)	NAb
	12 months
	Montelukast 3 months	1 (2.5)	53 (3.3)
Antihistaminergic agents, number of Rx preceding the index date, mean (SD)	AHIST 12 months	0.9 (1.5)	0.5 (1.2)	0.050
	AHIST 3 months	0.2 (0.6)	0.1 (0.5)	0.240
Nasal decongestants, number of Rx preceding the index date, mean (SD)	Xylomethazoline	0.9 (1.4)	0.7 (1.4)	0.364
	12 months
	Xylomethazoline	0.6 (0.9)	0.3 (0.7)	0.020
	3 months
Systemic antibiotics, number of Rx preceding the index date, mean (SD)	Antibiotics 12 months	1.2 (1.4)	0.7 (1.3)	0.024
	Antibiotics 3 months	0.2 (0.4)	0.1 (0.5)	0.337
Systemic corticosteroid use >15 days, patient moments with ≥1 Rx preceding the index date, N (%)	SCS 12 months	1 (2.5)	6 (0.4)	NAb
	SCS 3 months	0 (0.0)	3 (0.2)

Notes:

a Analyzed with a multiplicative intensity model.

b Not enough data for statistical testing.

Abbreviations: ICS, inhaled corticosteroid; SD, standard deviation; pMDI, pressurized metered dose inhaler; DPI, dry powder inhaler; SABA, short-acting beta-agonist; Rx, prescription; LABA, long-acting beta-agonist; SAMA, short-acting muscarinic antagonist; NA, not available; AHIST, antihistaminergic agent; SCS, systemic corticosteroid.

Table 2 Refill adherence to ICS in all children, in children with recent LABA use, and in children without recent LABA use

Adherence measures	Event moments (with asthma exacerbation)	Control moments (without asthma exacerbation)
All children, n=1,636	n=40	n=1,596
Refill adherence to ICS, mean (SD) (IQR, %)	67.9 (30.2) (49.6; 87.5)	54.2 (35.6) (28.5; 71.2)
Refill adherence to ICS ≥80%, n (%)	14 (35.0)	322 (20.2)
No recent LABA use n=1,342	n=27	n=1,315
Refill adherence to ICS, mean (SD) (IQR, %)	60.3 (28.9) (44.8; 72.6)	51.3 (35.8) (27.5; 65.6)
Refill adherence to ICS ≥80%, n (%)	5 (18.5)	226 (17.2)
Recent LABA use, n=294	n=13	n=281
Refill adherence to ICS, mean (SD) (IQR, %)	83.8 (27.4) (72.6; 102.6)	67.7 (31.6) (44.3; 86.5)
Refill adherence to ICS ≥80%, n (%)	9 (69.2)	96 (34.1)

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; SD, standard deviation; IQR, interquartile range.

Table 3 Association of refill adherence to ICS with the intensity of asthma exacerbations in children using LABA and in children not using LABA

Adherence measures	Intensity ratio of exacerbations (95% CI)
	Univariable	Multivariablea
No recent LABA use, n=1,342
Adherence to ICS ≥80%b	1.270 (0.471; 3.419); P=0.637	1.067 (0.391; 2.916); P=0.899
Recent LABA use, n=294
Adherence to ICS ≥80%b	4.459 (1.287; 15.454); P=0.018	4.340 (1.204; 15.640); P=0.025

Notes:

a Adjusted for confounding by recent SABA use.

b Refill adherence to inhaled corticosteroids.

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta-agonist; SABA, short-acting beta-agonist; CI, confidence interval.