A Retrospective Claims Database Study to Clarify Disease Burden of Severe Asthma Patients with Type 2 High or Low Inflammation

Figures & data

Figure 1 Study design. Index date: latest date of the eosinophil count assessed at least 1 year prior to the last visit. Baseline period: 1 year before the index date. Follow-up period: 1 year after the index date.

Figure 2 Analysis population.

Abbreviations: ICD-10, International Statistical Classification of Diseases and Related Health Problems, 10th Revision; ICS, inhaled corticosteroids; IgE, immunoglobulin E; OCS, oral corticosteroids; RWD-DB, Real World Data database.

Figure 3 Proportion of severe asthma patients classified by eosinophil counts and total IgE.

Abbreviations: EOS, eosinophil; IgE, immunoglobulin E.

Table 1 Patients’ Demographics and Baseline Characteristics in T2-High and T2-Low Populations

	T2-High	T2-Low
Total number of patients	599 (81.8)	133 (18.2)
Age, years, mean (SD)	64.6 (18.6)	65.5 (18.8)
Sex, female	329 (54.9)	101 (75.9)
BMI, kg/m^2, n = 283	n = 231	n = 52
Mean (SD)	23.5 (4.2)	23.2 (4.8)
Quan-Charlson comorbidity index score, mean (SD)	2.1 (1.8)	2.2 (1.7)
Comorbidities
Respiratory infection	36 (6.0)	4 (3.0)
Allergic rhinitis	163 (27.2)	33 (24.8)
Gastroesophageal reflux disease	142 (23.7)	33 (24.8)
Chronic obstructive pulmonary disease	143 (23.9)	40 (30.1)
Chronic paranasal sinusitis	49 (8.2)	6 (4.5)
Atopic dermatitis	15 (2.5)	1 (0.8)
Nasal polyp	5 (0.8)	0
Psychiatric disorder/anxiety/depression	36 (6.0)	15 (11.3)
Treatments
SABA	316 (52.8)	64 (48.1)
ICS	135 (22.5)	42 (31.6)
LABA	28 (4.7)	8 (6.0)
LAMA	151 (25.2)	35 (26.3)
ICS/LABA	530 (88.5)	110 (82.7)
ICS/LABA/LAMA	2 (0.3)	1 (0.8)
LTRA	409 (68.3)	79 (59.4)
Theophylline	267 (44.6)	49 (36.8)
OCS	278 (46.4)	69 (51.9)
Maintenance OCS	60 (10.0)	13 (9.8)
Injectable steroid	321 (53.6)	73 (54.9)
Biomarkers
Eosinophils, cells/µL, median (IQR)	248.2 (356.2)	70.0 (73.5)
Neutrophils, cells/µL, n = 616	n = 503	n = 113
Median (IQR)	4150 (2970)	4700 (3460)
Basophils, cells/µL, n = 726	n = 594	n = 132
Median (IQR)	33 (41)	21 (25)
Monocytes, cells/µL, median (IQR)	424 (235)	357 (230)
Lymphocytes, cells/µL, median (IQR)	1710 (974)	1558 (898)
Total IgE, IU/mL, median (IQR)	300.0 (649.1)	29.6 (34.3)
Specific IgE for perennial antigen
Tested	179 (29.9)	35 (26.3)
Positive in tested patients	91 (50.8)	7 (20.0)
CRP, mg/dL, n = 665	n = 545	n = 120
Median (IQR)	0.21 (0.56)	0.22 (0.77)

Note: Data are n (%) unless otherwise indicated.

Abbreviations: BMI, body mass index; CRP, C-reactive protein; ICS, inhaled corticosteroid; IgE, immunoglobulin E; IQR, interquartile range; LABA, long-acting beta agonist; LAMA, long-acting muscarinic antagonist; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; SABA, short-acting beta agonist; SD, standard deviation; T2, type 2.

Table 2 Asthma-Related Exacerbation Events and Medicine Cost During the Follow-Up Period in the T2-High and T2-Low Populations

	T2-High	T2-Low
Patients with asthma-related exacerbation, % (95% CI)
Composite outcome	30.6 (26.9–34.4)	34.6 (26.6–43.3)
OCS burst	18.4 (15.3–21.7)	21.1 (14.5–29.0)
Injectable steroid	21.9 (18.6–25.4)	26.3 (19.1–34.7)
Hospitalization	9.7 (7.4–12.3)	14.3 (8.8–21.4)
Medicine cost, JPY/patient-year
Total cost, median (IQR)	175,487 (298,926)	165,322 (334,775)
Asthma-related cost, median (IQR)	76,961 (127,287)	75,061 (123,764)

Abbreviations: CI, confidence interval; IQR, interquartile range; JPY, Japanese Yen; OCS, oral corticosteroids; T2, type 2.

Figure 4 Proportion of patients with asthma exacerbation in the T2-high population and T2-low population.

Abbreviations: OCS, oral corticosteroids; T2, type 2 phenotype.

Table 3 Asthma-Related Exacerbation Events and Medicine Cost During the Follow-Up Period in the T2-High Subpopulation

	Eosinophil Low-IgE High	Eosinophil High-IgE Low	Eosinophil High-IgE High
Patients (n)	158	107	334
Patients with asthma-related exacerbation, % (95% CI)
Composite outcome	34.8 (27.4–42.8)	25.2 (17.3–34.6)	30.2 (25.4–35.5)
OCS burst	19.6 (13.7–26.7)	13.1 (7.3–21.0)	19.5 (15.4–24.1)
Injectable steroid	28.5 (21.6–36.2)	17.8 (11.0–26.3)	20.1 (15.9–24.8)
Hospitalization	13.3 (8.4–19.6)	8.4 (3.9–15.4)	8.4 (5.6–11.9)
Medicine cost, JPY/patient-year
Total cost, median (IQR)	173,298 (360,285)	172,012 (307,078)	175,565 (260,316)
Asthma-related cost, median (IQR)	74,978 (126,719)	53,400 (118,125)	80,461 (130,966)

Abbreviations: CI, confidence interval; IgE, immunoglobulin E; IQR, interquartile range; JPY, Japanese Yen; OCS, oral corticosteroids; T2, type 2.

Table 4 Proportions of Patients and Asthma-Related Exacerbation Events During the Follow-Up Period in T2-High and T2-Low Populations Stratified by Different T2 Criteria

Cutoff Values for T2 Criteria^a			Patients With T2-High or T2-Low, %	Patients With Asthma Exacerbations, % (95% CI)
Eosinophil, Cells/μL	IgE, IU/mL
150	75	T2-high	81.8	30.6 (26.9–34.4)
		T2-low	18.2	34.6 (26.6–43.3)
150	30	T2-high	90.8	30.4 (26.9–34.0)
		T2-low	9.2	40.3 (28.5–53.0)
150	150	T2-high	76.9	30.0 (26.3–34.0)
		T2-low	23.1	35.5 (28.3–43.2)
300	75	T2-high	74.0	31.2 (27.3–35.3)
		T2-low	26.0	31.6 (25.0–38.7)

Note: ^aT2-high was defined as an eosinophil count ≥ cutoff value and/or an IgE level ≥ cutoff value; T2-low was defined as an eosinophil count < cutoff value and an IgE level < cutoff value.

Abbreviations: CI, confidence interval; IgE, immunoglobulin E; T2, type 2.