Exacerbations, treatment patterns, utilization, and costs before and after initiating of benralizumab for the treatment of severe eosinophilic asthma

Figures & data

Figure 1. Study diagram.

Figure 2. Patient selection diagram.

Figure 3. Changes in asthma exacerbations before and after starting benralizumab. McNemar’s χ² for counts of patients and paired t-test for mean exacerbations.

Table

Diseases	ICD-10-CM diagnosis code
Acute asthma exacerbation^a	J45.21, J42.22, J45.31, J45.32, J45.41, J45.42, J45.51, J45.52, J45.901, J45.902
Acute myocardial infarction	I21%
Allergic bronchopulmonary aspergillosis (ABPA)	B44.81
Allergic conjunctivitis	H10.45
Allergic rhinitis	J30.1, J30.2, J30.5, J30.81, J30.89, J30.9
Asthma	J45%
Atopic dermatitis	L20.89, L20.9
Autoimmune diseases^b	L63%, M45%, M08.1, K90.0, N03, L50.8, K50%, M31.5, M31.6, E05.0, E06.0, D55%, D59%, D69.3, G35%, K74.3, L40%, J84.1, M05, M06, M08.0, M08.2, M08.3, M08.4, M35.0, M32%, M34%, E10, K51, L80%
Chronic idiopathic urticaria	L50.1, L50.9, L50.8
Chronic obstructive pulmonary disease (COPD)	J41%–J44%
Congestive heart failure	I09.9, I11.0, I13.0, I13.2, I25.5, I42.0, I42.5-I42.9, I43, I50, P29.0
Eosinophilic esophagitis (EOE)	K20.0
Eosinophilic granulomatosis with poly angiitis (EGPA)	M30.1
Gastroesophageal reflux disease	K21%
Hypereosinophilic syndrome/idiopathic hypereosinophilic syndrome (HES)	D72%
Hyperlipidemia	E78.5
Hypertension	I10%
Infections—Non-respiratory	G00%, G01%, G02%, G03%, R65.2, R65.21, T81.12, T81.4%, L03%, L02%, L08%, N39.0, N30.0%, N10%
Infections—Respiratory	J00-06%, J12%, J13%, J14%, J15%, J16%, J17%, J18%, J20%
Nasal polyps	J33.1, J33.8, J33.0, J33.9
Obesity	E66%
Obstructive sleep apnea	G47.33

^aAcute asthma exacerbation includes asthma with (acute) exacerbation and asthma with status.

^bAutoimmune diseases include alopecia areata, ankylosing spondylitis, celiac disease, chronic glomerulonephritis, chronic urticaria, Crohn’s disease, giant cell arteritis, Graves’ disease, Hashimoto thyroiditis, hemolytic anemia, immune thrombocytopenia purpura, multiple sclerosis, primary biliary cirrhosis, psoriasis, psoriatic arthritis, pulmonary fibrosis, rheumatoid arthritis, Sjӧgren syndrome, systemic lupus erythematosus, systemic sclerosis, type 1 diabetes, ulcerative colitis, and vitiligo.

Table 1. Patient demographic and clinical characteristics during baseline and on index date for the claims sample and the medical record sample.

	Claims sample	Medical record sample
Number of patients, N	506	123
Age (years), n (%)
Mean (SD)	52.2 (14.3)	53.1 (13.5)
Age categories
12–17	15 (3%)	≤10
18–39	67 (13.2%)	11 (8.9%)
40–64	344 (68%)	88 (71.5%)
65–74	60 (11.9%)	17 (13.8%)
≥75	20 (4%)	≤10
Gender, n (%)
Female	350 (69.2%)	85 (69.1%)
Plan type, n (%)
PPO	305 (60.3%)	73 (59.4%)
HMO	128 (25.3%)	28 (22.8%)
CDHP	73 (14.4%)	22 (17.9%)
Insurance type, n (%)
Commercial	456 (90.1%)	104 (84.6%)
Medicare advantage	24 (4.7%)	15 (12.2%)
Medicare other (Supplemental and Part D)	26 (5.1%)	≤10
Residence region, n (%)
Northeast	89 (17.6%)	22 (17.9%)
Midwest	87 (17.2%)	27 (22.0%)
South	207 (40.9%)	42 (34.2%)
West	102 (20.2%)	29 (23.6%)
Missing	21 (4.2%)	3 (2.4%)
Year of index date, n (%)
2017	≤10	≤10
2018	179 (35.4%)	51 (41.5%)
2019	197 (38.9%)	34 (27.6%)
2020	126 (24.9%)	24 (19.5%)
2021	N/A	12 (9.8%)
Index treatment physician specialty^a, n (%)
Allergist/immunologist	196 (38.7%)	75 (61.0%)
Pulmonologist	170 (33.6%)	36 (29.3%)
Primary care physician^b	19 (3.8%)	≤10
Nonphysician clinician^c	45 (8.9%)	≤10
Other^d	67 (13.2%)	≤10
Unknown/missing	≤10	≤10
Quan-Charlson Comorbidity Index (QCI), continuous
Mean (SD)	1.6 (1.1)	1.7 (1.2)
Median (IQR)	1.0 (1.0-2.0)	1.0 (1.0-2.0)
QCI, categorical, n (%)
0	0 (0%)	0 (0.0%)
1	369 (72.9%)	85 (69.1%)
2	41 (8.1%)	11 (8.9%)
≥3	96 (19%)	27 (22.0%)
Other clinical conditions, n (%)
Allergic bronchopulmonary aspergillosis (ABPA)	13 (2.6%)	≤10
Allergic conjunctivitis	30 (5.9%)	13 (10.6%)
Allergic rhinitis	362 (71.5%)	91 (74.0%)
Atopic dermatitis	18 (3.6%)	≤10
Autoimmune diseases	37 (7.3%)	≤10
Chronic idiopathic urticaria	23 (4.5%)	≤10
Chronic obstructive pulmonary disease (COPD)	145 (28.7%)	33 (26.8%)
Congestive heart failure	24 (4.7%)	≤10
Eosinophilia	79 (15.6%)	12 (9.8%)
Hypereosinophilic syndrome (HES)	0 (0%)	0 (0.00%)
Eosinophilic esophagitis (EOE)	12 (2.4%)	≤10
Eosinophilic granulomatosis with poly angiitis (EGPA)	≤10	≤10
Gastroesophageal reflux disease	213 (42.1%)	61 (49.6%)
Hyperlipidemia	143 (28.3%)	35 (28.5%)
Hypertension	238 (47.0%)	54 (43.9%)
Infections	396 (78.3%)	87 (70.7%)
Respiratory infection	379 (74.9%)	75 (61.0%)
Non-respiratory infection	103 (20.4%)	31 (25.2%)
Nasal polyps	103 (20.4%)	26 (21.1%)
Obesity	187 (37.0%)	39 (31.7%)
Obstructive sleep apnea	138 (27.3%)	34 (27.6%)

Note. HMO, Health Maintenance Organization; PPO, Preferred Provider Organization; CDHP, Consumer-Driven Health Plan.

Counts ≤ 10 are blinded for patient privacy.

^aBased on the physician specialty on index date; multiple specialties were reclassified based on the following hierarchy: Allergist/Immunologist > pulmonologist > primary care physician > non-physician clinician > others > unknown/missing. For specialty listed as facility, other, or unknown/missing, claims for outpatient visits in the 30 days preceding the index date were assessed to determine if an allergist/immunologist, pulmonologist, or primary care physician was seen. If so, the specialty was recoded as such. For medical records, providers who ordered spirometry tests were targeted for record abstraction.

^bPrimary Care Physician includes general/family practice, internal medicine, and geriatric medicine.

^cNonphysician clinician includes nurse practitioner and physician assistant.

^dOther specialties include: cardiology, cardiothoracic surgery, critical care, emergency medicine, facility, gastroenterology, hematology/oncology, infectious disease, neurology, obstetrics gynecology (ob/gyn), otolaryngology, rheumatology, sports medicine, surgery, urology.

Table 2. Asthma Control Test and symptoms before and after starting benralizumab.

Measure	Baseline	Follow-up	p Value
ACT score (n = 47), n (%)
<19	34 (72.3%)	21 (44.7%)	<.01
≥19	13 (27.7%)	26 (55.3%)
Mean (SD) | median	14.7 (6.1) | 14	18.4 (6.1) | 19
Asthma symptoms (n = 123)
Coughing
Patients with ≥ 1, n (%)	101 (82.1%)	72 (58.5%)
Wheezing
Patients with ≥ 1, n (%)	87 (70.7%)	57 (46.3%)
Shortness of breath
Patients with ≥ 1, n (%)	95 (77.2%)	64 (52.0%)
Chest tightness/pain/pressure
Patients with ≥ 1, n (%)	66 (53.7%)	32 (26.0%)

Table 3. Asthma medication use before and after starting benralizumab.

	12 m Pre-index	12 m Post-index	p Value^a
Number of patients, N	722	722
Asthma controller medications
Inhaled corticosteroids (ICS)
≥1 Fill, n (%)	262 (36.3%)	181 (25.1%)	<.001
Number of fills
Mean (SD)	1.4 (2.9)	0.9 (2.2)	<.001
Median (IQR)	0 (0–1)	0 (0–0.8)
Long-acting beta agonists (LABA)
≥1 Fill, n (%)	27 (3.7%)	18 (2.5%)	.066
Number of fills
Mean (SD)	0.1 (0.9)	0.1 (0.7)	.087
Median (IQR)	0 (0–0)	0 (0–0)
ICS + LABA combination^b
≥1 fill, n (%)	624 (86.4%)	525 (72.7%)	<.001
Number of fills
Mean (SD)	4.2 (3.4)	3.4 (3.5)	<.001
Median (IQR)	3 (2-6)	2 (0-5)
Long-acting antimuscarinic antagonists (LAMAs)
≥1 Fill, n (%)	341 (47.2%)	253 (35.0%)	<.001
Number of fills
mean (SD)	1.6 (2.5)	1.6 (2.9)	.575
median (IQR)	0 (0–2)	0 (0–2)
ICS + LABA + LAMA combination^b
≥1 Fill, n (%)	270 (37.4%)	245 (33.9%)	.052
Number of fills
Mean (SD)	1.5 (2.6)	1.8 (3.1)	.017
Median (IQR)	0 (0–2)	0 (0–3)
Biologic asthma medications
Omalizumab
≥1 Fill, n (%)	107 (14.8%)	40 (5.5%)	<.001
Number of fills
Mean (SD)	1.4 (4.1)	0.3 (1.9)	<.001
Median (IQR)	0 (0–0)	0 (0–0)
Mepolizumab
≥1 Fill, n (%)	59 (8.2%)	22 (3.0%)	<.001
Number of fills
Mean (SD)	0.5 (2.1)	0.1 (1)	<.001
Median (IQR)	0 (0–0)	0 (0–0)
Reslizumab
≥1 Fill, n (%)	13 (1.8%)	≤10	.006
Number of fills
Mean (SD)	0.2 (1.4)	0 (0.3)	.006
Median (IQR)	0 (0-0)	0 (0-0)
Dupilumab
≥1 Fill, n (%)	22 (3.0%)	45 (6.2%)	.006
Number of fills
Mean (SD)	0.2 (1.2)	0.3 (1.2)	.120
Median (IQR)	0 (0–0)	0 (0–0)
Asthma rescue medications
Inhaled short-acting beta agonists (SABA)
≥1 Fill, n (%)	665 (92.1%)	509 (70.5%)	<.001
Number of fills
Mean (SD)	5.3 (5.1)	3.3 (4.4)	<.001
Median (IQR)	4 (2–7)	2 (0–4)
Systemic corticosteroids
≥1 Fill, n (%)	722 (100%)	555 (76.9%)	<.001
Number of fills
Mean (SD)	7.7 (5.1)	3.8 (7.1)	<.001
Median (IQR)	6 (4-10)	2 (1-5)
≥1 Fill, n (%)	722 (100%)	555 (76.9%)	<.001
≥2 Fills, n (%)	722 (100%)	428 (59.3%)	<.001
≥3 Fills, n (%)	675 (93.5%)	326 (45.2%)	<.001
≥4 Fills, n (%)	596 (82.5%)	254 (35.2%)	<.001
Oral corticosteroids (OCS)
≥1 Fill, n (%)	719 (99.6%)	506 (70.1%)	<.001
Number of fills
Mean (SD)	6.1 (3.9)	2.6 (3.5)	<.001
Median (IQR)	5 (3–8)	1 (0–3.8)
OCS dependent^c, n (%)	180 (24.9%)	96 (13.3%)	<.001
Injectable corticosteroids
≥1 Fill, n (%)	406 (56.2%)	292 (40.4%)	<.001
Number of fills
Mean (SD)	1.6 (2.4)	1.2 (5.9)	.039
Median (IQR)	1 (0–2)	0 (0–1)

Note. SD, standard deviation; IQR, interquartile range; m, month.

^ap Values for categorical variables were obtained using McNemar’s or binomial exact test and for continuous variables were obtained using paired t-test. Bolded p values indicate significance at the alpha = .05 level. 

^bICS + LABA/ICS + LABA + LAMA combinations as a single inhaler or as separate inhalers used concurrently.

^cPatients with at least 180 days of supply of OCS for 12 months or at least 450 mg of OCS over 90 days (average daily dose of 5 mg).