Disease burden and treatment adherence among children and adolescent patients with asthma

Figures & data

Figure 1. Study design scheme for (A) the asthma cohort and (B) the treatment cohorts. HRU, healthcare resource utilization; ICS: inhaled corticosteroid; LABA: long-acting beta₂ agonist.

Table 1. Baseline characteristics: asthma cohort.^a

Characteristics	Overall Age 5–17 years ( N  = 186,868)	Children Age 5–11 years ( n  = 112,689)	Adolescents Age 12–17 years ( n  = 74,179)
Age, years, mean ± SD [median]^b	10.5 ± 3.6 [10.0]	7.9 ± 2.0 [8.0]	14.3 ± 1.7 [14.0]
Female, n (%)^b	75,406 (40.4)	42,549 (37.8)	32,857 (44.3)
Asthma medication, n (%)
≥1 ICS	47,982 (25.7)	33,380 (29.6)	14,602 (19.7)
≥1 LTRA	36,619 (19.6)	22,531 (20.0)	14,088 (19.0)
≥1 ICS/LABA	16,367 (8.8)	7,171 (6.4)	9,196 (12.4)
≥1 SABA	82,689 (44.2)	49,718 (44.1)	32,971 (44.4)
≥1 OCS	44,764 (24.0)	29,979 (26.6)	14,785 (19.9)
≥1 Asthma exacerbation, n (%)^c	37,405 (20.0)	25,704 (22.8)	11,701 (15.8)
≥1 Moderate exacerbation^c	33,223 (17.8)	22,594 (20.0)	10,629 (14.3)
≥1 Severe exacerbation^c	4,182 (2.2)	3,110 (2.8)	1,072 (1.4)
Asthma-related HRU, n (%)
Inpatient visit	4,157 (2.2)	3,091 (2.7)	1,066 (1.4)
ED visit	20,669 (11.1)	14,204 (12.6)	6,465 (8.7)
Outpatient visit	152,702 (81.7)	94,660 (84.0)	58,042 (78.2)

Notes: ED: emergency department; HRU: healthcare resource utilization; ICS: inhaled corticosteroid; LABA: long-acting beta₂ agonist; LTRA: leukotriene receptor antagonist; OCS: oral corticosteroid; SABA: short-acting beta₂ agonist; SD: standard deviation.

^aBaseline data reflect 12 months prior to the index date.

^bBaseline characteristics including age and sex were evaluated on the index date.

^cModerate exacerbations were defined as an asthma-related ED visit or outpatient visit with systemic/oral corticosteroid dispensing within ±5 days. Severe exacerbations were defined as an asthma-related inpatient visit or ED visit resulting in an inpatient visit within +1 day. Patients with two or more exacerbations within 14 days of each other were considered as one exacerbation and classified according to the highest severity.

Table 2. Follow-up treatment patterns: asthma cohort.

Medication use	Overall Age 5–17 years ( N  = 186,868)	Children Age 5–11 years ( n  = 112,689)	Adolescents Age 12–17 years ( n  = 74,179)
Observation period, days, mean ± SD	1,041.4 ± 440.5	1,039.1 ± 439.3	1,044.8 ± 442.5
Asthma maintenance medications, n (%)
ICS	56,644 (30.3)	39,020 (34.6)	17,624 (23.8)
LTRA	45,899 (24.6)	28,541 (25.3)	17,358 (23.4)
ICS/LABA	23,235 (12.4)	11,548 (10.2)	11,687 (15.8)
LAMA	331 (0.2)	127 (0.1)	204 (0.3)
LABA	158 (0.1)	68 (0.1)	90 (0.1)
Mast cell stabilizers	85 (0.0)	50 (0.0)	35 (0.0)
Methylxantines	87 (0.0)	27 (0.0)	60 (0.1)
Biologics	110 (0.1)	33 (0.0)	77 (0.1)
Asthma rescue medications, n (%)
SABA	94,579 (50.6)	56,743 (50.4)	37,836 (51.0)
OCS	62,767 (33.6)	39,049 (34.7)	23,718 (32.0)
SAMA or SABA/SAMA	4,390 (2.4)	2,724 (2.4)	1,666 (2.2)

ICS: inhaled corticosteroid; LABA: long-acting beta₂ agonist; LAMA: long-acting muscarinic antagonist; LTRA: leukotriene receptor antagonist; OCS: oral corticosteroid; SABA: short-acting beta₂ agonist; SAMA: short-acting muscarinic antagonist; SD: standard deviation.

Table 3. Follow-up asthma-related HRU and healthcare costs: asthma cohort and treatment cohort.

HRU and healthcare cost measures^a	Asthma cohort ( N  = 186,868)			Treatment cohort ( n  = 57,523)
	Overall Age 5–17 years ( N  = 186,868)	Children Age 5–11 years ( n  = 112,689)	Adolescents Age 12–17 years ( n  = 74,179)	Twice-daily ICS ( n  = 47,276)	Twice-daily ICS/LABA ( n  = 10,247)
Observation period, days, mean ± SD	1,041.4 ± 440.5	1,039.1 ± 439.3	1,044.8 ± 442.5	70.0 ± 79.8	82.5 ± 91.1
Rate of asthma-related HRU event, PPPY
Inpatient visits	0.012	0.013	0.009	0.016	0.013
ED visits	0.069	0.078	0.055	0.082	0.067
Outpatient visits	1.073	1.158	0.945	2.807	2.809
Asthma-related HRU event, n (%)
Inpatient visits	4,711 (2.5)	3,313 (2.9)	1,398 (1.9)	136 (0.3)	27 (0.3)
ED visits	21,425 (11.5)	14,439 (12.8)	6,986 (9.4)	666 (1.4)	137 (1.3)
Outpatient visits	127,091 (68.0)	80,256 (71.2)	46,835 (63.1)	16,056 (34.0)	3,835 (37.4)
Asthma-related costs, 2018 US$, PPPY, mean ± SD
Total (medical + pharmacy) costs	$521 ± 61,809	$525 ± 49,777	$517 ± 76,550	$1,365 ± 24,925	$1,920 ± 26,367
Total medical costs	$248 ± 51,728	$247 ± 40,250	$250 ± 65,419	$485 ± 22,290	$493 ± 22,356
Inpatient costs	$60 ± 25,131	$69 ± 24,139	$47 ± 26,560	$70 ± 16,009	$81 ± 15,294
ED costs	$24 ± 4,500	$26 ± 4,432	$21 ± 4,599	$36 ± 4,173	$29 ± 3,660
Outpatient costs	$163 ± 41,549	$151 ± 27,720	$182 ± 56,400	$379 ± 11,746	$383 ± 14,037
Pharmacy costs	$274 ± 26,686	$278 ± 23,823	$267 ± 30,525	$880 ± 9,482	$1,426 ± 12,722

Notes: ED: emergency department; HRU: healthcare resource utilization; ICS: inhaled corticosteroid; LABA: long-acting beta₂ agonist; PPPY: per patient per year; SD: standard deviation; US$: United States dollars.

^aHRU and healthcare costs were evaluated while the patients were on treatment.

Table 4. Baseline characteristics: treatment cohorts.

Characteristics	Twice-daily ICS ( n  = 47,276)	Twice-daily ICS/LABA ( n  = 10,247)
Age, years, mean ± SD	9.9 ± 3.7	12.5 ± 3.3
Female, n (%)	20,748 (43.9)	4,938 (48.2)
Prescribing provider specialty, n (%)^a
Primary care	30,514 (64.5)	4,984 (48.6)
Respiratory specialist	6,054 (12.8)	2,568 (25.1)
Asthma medication, n (%)
≥1 ICS	0 (0.0)	614 (6.0)
≥1 LTRA	10,929 (23.1)	3,163 (30.9)
≥1 SABA	30,940 (65.4)	6,785 (66.2)
≥1 OCS	18,399 (38.9)	4,164 (40.6)
≥1 Asthma exacerbation, n (%)^b	10,368 (21.9)	2,298 (22.4)
≥1 Moderate exacerbation^b	9,053 (19.1)	2,102 (20.5)
≥1 Severe exacerbation^b	1,315 (2.8)	196 (1.9)
Asthma-related HRU, n (%)
Inpatient visit	1,368 (2.9)	198 (1.9)
ED visit	3,732 (7.9)	775 (7.6)
Outpatient visit	36,539 (77.3)	8,460 (82.6)

Notes: ED: emergency department; HRU: healthcare resource utilization; ICS: inhaled corticosteroid; LABA: long-acting beta₂ agonist; LTRA: leukotriene receptor antagonist; OCS: oral corticosteroid; SABA: short-acting beta₂ agonist; SD: standard deviation.

^aPatients were classified as having either a respiratory (pulmonologist, allergist) or primary care (pediatrician, internal medicine, family medicine practitioner) specialist as a prescribing provider specialty. For patients with claims indicating both respiratory and primary care specialties, the claim closest to the index date was used to determine the physician specialty.

^bModerate exacerbations were defined as an asthma-related ED visit or outpatient visit with systemic/oral corticosteroid dispensing within ±5 days. Severe exacerbations were defined as an asthma-related inpatient visit or ED visit resulting in an inpatient visit within +1 day. Patients with two or more exacerbations within 14 days of each other were considered as one exacerbation and classified according to the highest severity.

Table 5. Follow-up treatment patterns: treatment cohorts.

	Twice-daily ICS ( n  = 47,276)	Twice-daily ICS/LABA ( n  = 10,247)
Medication use
Observation period, days, mean ± SD [median]	341.3 ± 60.5 [366.0]	342.6 ± 59.7 [366.0]
Time to treatment discontinuation, days, mean ± SD [median]^a	148.3 ± 130.8 [89.0]	160.7 ± 132.5 [119.0]
Twice-daily ICS dosage at initiation, n (%)^b	41,333 (87.8)	5,174 (50.5)
Low	15,134 (36.6)	2,365 (45.7)
Medium	20,697 (50.1)	2,177 (42.1)
High	5,502 (13.3)	632 (12.2)
Asthma maintenance medications, n (%)
ICS	47,276 (100.0)	953 (9.3)
ICS/LABA	2,577 (5.5)	10,247 (100.0)
LTRA	14,963 (31.7)	4,260 (41.6)
LAMA	30 (0.1)	48 (0.5)
LABA	36 (0.1)	10 (0.1)
Mast cell stabilizers	17 (0.0)	4 (0.0)
Methylxanthines	5 (0.0)	6 (0.1)
Biologics	2 (0.0)	0 (0.0)
Asthma rescue medications, n (%)
SABA	38,003 (80.4)	7,621 (74.4)
OCS	19,490 (41.2)	4,055 (39.6)
Adherence measures
At 180 days
Patients, n	44,814	9,716
PDC, mean ± SD [median]	0.30 ± 0.20 [0.17]	0.34 ± 0.22 [0.32]
Proportion with PDC ≥0.5, n (%)	8,706 (19.4)	2,592 (26.7)
Proportion with PDC ≥0.8, n (%)	1,915 (4.3)	595 (6.1)
At 365 days
Patients, n	37,943	8,341
PDC, mean ± SD [median]	0.21 ± 0.18 [0.16]	0.24 ± 0.20 [0.16]
Proportion with PDC ≥0.5, n (%)	2,721 (7.2)	887 (10.6)
Proportion with PDC ≥0.8, n (%)	694 (1.8)	230 (2.8)

Notes: ICS: inhaled corticosteroid; LABA: long-acting beta₂ agonist; LAMA: long-acting muscarinic antagonist; LTRA: leukotriene receptor antagonist; OCS: oral corticosteroid; PDC: proportion of days covered; SABA: short-acting beta₂ agonist; SD: standard deviation.

^aDuration of treatment was calculated as number of days between the first and end of last dispensing (i.e. start of last dispensing plus days’ supply) of the same class or end of follow-up, whichever occurred first.

^bIndex twice-daily ICS or the ICS component of the index twice-daily ICS/LABA was categorized based on Global Initiative for Asthma 2016/2018 clinical guidelines and Guidelines for the Diagnosis and Management of Asthma. Not all ICS dosages could be categorized as low, medium, and high ICS dosage as some brands/generics cannot be categorized by dosage and some brands/generics cannot be categorized for a specific age group.

Figure 2. Kaplan-Meier rates of persistence^a to twice-daily ICS or ICS/LABA. Notes: ^aNon-persistence (i.e. discontinuation) was defined as a gap of >45 days in days’ supply of medication (i.e. between the end of supply of one dispensing to the date of the following dispensing or the end of the follow-up period). ICS: inhaled corticosteroid; LABA: long-acting beta₂ agonist.

Data sharing statement

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