Impact of Race on Baseline Asthma Severity and Response to Biologic Therapy in the First 12 Months Post Biologic Initiation

1 Study Overview

1.1 Background

The purpose of the study is to identify racial and socioeconomic factors that may impact outcomes in patients with moderate to severe asthma. The first phase of the study will describe the moderate to severe asthma patient population at VUMC prescribed biologic asthma therapies and identify differences in rates of healthcare utilization, asthma exacerbations (as determined by refill frequency of short-acting beta agonist (SABA) inhalers, systemic corticosteroids prescribed, hospitalizations/urgent care visits), clinical response to treatment (as defined as change in FEV1 in mL from baseline, SABA inhaler and systemic corticosteroid frequency), adherence and persistence to specialty medications, and clinic engagement by racial and socio-economic status within the healthcare system.

1.2 Methods

Retrospective cohort review of patients prescribed benralizumab, dupilumab, mepolizumab and omalizumab from 01/01/2019-6/30/2022.

1.3 Outcomes

Primary Outcome: Determine if there is an association between race, ethnicity, or socioeconomic status (SES) and baseline disease status at the time of biologic initiation.

2 Patient Demographics and Characteristics

2.1 Main Summary

Characteristic N Overall, N = 2151 Black or African American, N = 591 Other/Unknown, N = 81 White, N = 1481
Age at referral 215



    Mean (SD)
44 (21) 34 (20) 39 (21) 48 (20)
    Median (IQR)
48 (26, 60) 33 (16, 52) 41 (21, 47) 53 (37, 62)
    Range
6, 84 7, 79 15, 80 6, 84
Age Category 215



    Adolescent (<= 18)
44 (20.5%) 22 (37.3%) 2 (25.0%) 20 (13.5%)
    Adult (19-64)
133 (61.9%) 35 (59.3%) 5 (62.5%) 93 (62.8%)
    Elder adult (65+)
38 (17.7%) 2 (3.39%) 1 (12.5%) 35 (23.6%)
Gender 215



    Female
118 (54.9%) 33 (55.9%) 7 (87.5%) 78 (52.7%)
    Male
97 (45.1%) 26 (44.1%) 1 (12.5%) 70 (47.3%)
Race 215



    White
148 (68.8%) 0 (0%) 0 (0%) 148 (100.0%)
    Black or African American
59 (27.4%) 59 (100.0%) 0 (0%) 0 (0%)
    Middle Eastern
3 (1.40%) 0 (0%) 3 (37.5%) 0 (0%)
    American Indian or Alaska Native
2 (0.93%) 0 (0%) 2 (25.0%) 0 (0%)
    Native Hawaiian or Other Pacific Islander
1 (0.47%) 0 (0%) 1 (12.5%) 0 (0%)
    Race not mentioned
1 (0.47%) 0 (0%) 1 (12.5%) 0 (0%)
    Mixed race
1 (0.47%) 0 (0%) 1 (12.5%) 0 (0%)
Ethnicity 215



    None of these
70 (32.6%) 25 (42.4%) 2 (25.0%) 43 (29.1%)
    Not Hispanic, Latino/a, or Spanish origin
67 (31.2%) 17 (28.8%) 2 (25.0%) 48 (32.4%)
    Unknown
59 (27.4%) 14 (23.7%) 1 (12.5%) 44 (29.7%)
    Prefer not to answer
5 (2.33%) 2 (3.39%) 0 (0%) 3 (2.03%)
    Unable to provide
4 (1.86%) 1 (1.69%) 0 (0%) 3 (2.03%)
    Mexican, Mexican American, or Chicano/a
3 (1.40%) 0 (0%) 2 (25.0%) 1 (0.68%)
    Null
3 (1.40%) 0 (0%) 0 (0%) 3 (2.03%)
    Other Hispanic, Latino/a, or Spanish origin
2 (0.93%) 0 (0%) 0 (0%) 2 (1.35%)
    Hispanic or Latino
1 (0.47%) 0 (0%) 1 (12.5%) 0 (0%)
    Decline to Answer
1 (0.47%) 0 (0%) 0 (0%) 1 (0.68%)
Diagnosis 215



    Moderate-persistent asthma
113 (52.6%) 27 (45.8%) 6 (75.0%) 80 (54.1%)
    Severe-persistent asthma
102 (47.4%) 32 (54.2%) 2 (25.0%) 68 (45.9%)
Medication 215



    Dupixent
179 (83.3%) 54 (91.5%) 7 (87.5%) 118 (79.7%)
    Nucala
23 (10.7%) 2 (3.39%) 1 (12.5%) 20 (13.5%)
    Xolair
7 (3.26%) 2 (3.39%) 0 (0%) 5 (3.38%)
    Fasenra
6 (2.79%) 1 (1.69%) 0 (0%) 5 (3.38%)
Insurance Type 215



    Commercial
115 (53.5%) 27 (45.8%) 5 (62.5%) 83 (56.1%)
    Medicare
48 (22.3%) 8 (13.6%) 0 (0%) 40 (27.0%)
    Medicaid
35 (16.3%) 19 (32.2%) 2 (25.0%) 14 (9.46%)
    Tricare
6 (2.79%) 4 (6.78%) 1 (12.5%) 1 (0.68%)
    Commercial/Medicaid
4 (1.86%) 0 (0%) 0 (0%) 4 (2.70%)
    None
4 (1.86%) 1 (1.69%) 0 (0%) 3 (2.03%)
    Medicare/Medicaid
2 (0.93%) 0 (0%) 0 (0%) 2 (1.35%)
    Other
1 (0.47%) 0 (0%) 0 (0%) 1 (0.68%)
Insurance Other 1



    WORKERS COMPENSATION OTHER
1 (100.0%) 0 (NA%) 0 (NA%) 1 (100.0%)
    Not Applicable
214 59 8 147
Smoking 215



    Never smoker/Never exposure or Unknown
129 (60.0%) 36 (61.0%) 7 (87.5%) 86 (58.1%)
    Exposure
21 (9.77%) 9 (15.3%) 1 (12.5%) 11 (7.43%)
    Previous
43 (20.0%) 7 (11.9%) 0 (0%) 36 (24.3%)
    Current
22 (10.2%) 7 (11.9%) 0 (0%) 15 (10.1%)
Distance to care (miles) 211



    Mean (SD)
3.4 (3.4) 2.8 (2.7) 3.9 (3.3) 3.7 (3.6)
    Median (IQR)
2.0 (1.0, 5.2) 2.0 (1.3, 3.1) 2.7 (1.5, 4.5) 2.1 (0.9, 5.9)
    Range
0.1, 15.1 0.2, 12.4 1.5, 10.6 0.1, 15.1
    Not Applicable
4 1 0 3
1 n (%)

2.2 Smoking

Smoking type Total (N = 64)
Cigarette 57 (89.1%)
Marijuana 6 (9.4%)
Chew 5 (7.8%)
Vaping 4 (6.2%)
Cigar 2 (3.1%)
Pipe 1 (1.6%)
Characteristic Black or African American, N = 591 Other/Unknown, N = 81 White, N = 1481
Smoking status


    Never smoker/Never exposure or Unknown 36 (61.0%) 7 (87.5%) 86 (58.1%)
    Exposure 9 (15.3%) 1 (12.5%) 11 (7.43%)
    Previous 7 (11.9%) 0 (0%) 36 (24.3%)
    Current 7 (11.9%) 0 (0%) 15 (10.1%)
1 n (%)
Characteristic Hispanic or Latino, N = 61 Not Hispanic, Latino/a, or Spanish origin, N = 1371 Unknown/Null/Decline or prefer not to answer/Unable to provide, N = 721
Smoking status


    Never smoker/Never exposure or Unknown 3 (50.0%) 83 (60.6%) 43 (59.7%)
    Exposure 3 (50.0%) 11 (8.03%) 7 (9.72%)
    Previous 0 (0%) 31 (22.6%) 12 (16.7%)
    Current 0 (0%) 12 (8.76%) 10 (13.9%)
1 n (%)

3 Baseline Disease Status

3.1 Descriptive Summaries

3.1.1 Main Summary

Characteristic N Overall, N = 2151 White, N = 1481 Black or African American, N = 591 Other/Unknown, N = 81
Degree of asthma severity 215



    moderate
106 (49.3%) 75 (50.7%) 27 (45.8%) 4 (50.0%)
    severe
109 (50.7%) 73 (49.3%) 32 (54.2%) 4 (50.0%)
Covid dx within 12 months prior to biologic initiation 215



    No
200 (93.0%) 137 (92.6%) 55 (93.2%) 8 (100.0%)
    Yes
15 (6.98%) 11 (7.43%) 4 (6.78%) 0 (0%)
1 n (%)

3.1.2 Previously treated with clinic administered medication

Value Other/Unknown (N = 8) Black or African American (N = 59) White (N = 148) Total (N = 215)
None of the above 6 (75%) 54 (91.5%) 127 (85.8%) 187 (87%)
Xolair 2 (25%) 3 (5.1%) 13 (8.8%) 18 (8.4%)
Nucala 1 (12.5%) 2 (3.4%) 5 (3.4%) 8 (3.7%)
Fasenra 0 (0%) 1 (1.7%) 4 (2.7%) 5 (2.3%)
Cinqair 1 (12.5%) 0 (0%) 1 (0.7%) 2 (0.9%)

4 PDC and Persistence

Characteristic N N = 1571
PDC 157
    Mean (SD)
0.90 (0.14)
    Median (IQR)
0.96 (0.88 - 1.00)
    Range
0.32 - 1.00
Fills 157
    Mean (SD)
10.80 (3.94)
    Median (IQR)
12.00 (8.00 - 14.00)
    Range
3.00 - 26.00
Number of switches 157
    0
148 (94.3%)
    1
8 (5.10%)
    3
1 (0.64%)
Gap days 157
    Mean (SD)
32.32 (47.17)
    Median (IQR)
13.00 (1.00 - 35.00)
    Range
0.00 - 238.00
Gaps >90 days 157
    0
149 (94.9%)
    1
8 (5.10%)
1 n (%)
Characteristic N White, N = 1041 Black or African American + Other, N = 531 p-value2
PDC 157

0.104
    Mean (SD)
0.92 (0.12) 0.87 (0.17)
    Median (IQR)
0.97 (0.91 - 1.00) 0.95 (0.74 - 0.99)
    Range
0.43 - 1.00 0.32 - 1.00
Fills 157

0.461
    Mean (SD)
11.00 (4.01) 10.42 (3.79)
    Median (IQR)
12.00 (8.75 - 14.00) 12.00 (8.00 - 14.00)
    Range
3.00 - 26.00 3.00 - 15.00
Number of switches 157

0.030
    0
96 (92.3%) 52 (98.1%)
    1
8 (7.69%) 0 (0%)
    3
0 (0%) 1 (1.89%)
Gap days 157

0.095
    Mean (SD)
26.32 (41.28) 44.11 (55.54)
    Median (IQR)
7.50 (0.75 - 29.50) 17.00 (2.00 - 85.00)
    Range
0.00 - 202.00 0.00 - 238.00
Gap days (percent) 157

0.126
    Mean (SD)
8.33 (12.32) 13.48 (16.80)
    Median (IQR)
2.73 (0.21 - 9.61) 5.31 (0.55 - 25.66)
    Range
0.00 - 56.74 0.00 - 68.00
Gaps >90 days 157

0.718
    0
98 (94.2%) 51 (96.2%)
    1
6 (5.77%) 2 (3.77%)
1 n (%)
2 Wilcoxon rank sum test; Fisher’s exact test

5 Follow-up

5.1 Descriptive Summary

Characteristic N Overall, N = 1851 White, N = 1261 Black or African American, N = 521 Other/Unknown, N = 71
Age 185



    Mean (SD)
43 (20) 47 (20) 36 (20) 33 (14)
    Median (IQR)
46 (24, 58) 52 (36, 61) 36 (16, 54) 40 (20, 44)
    Range
6, 84 6, 84 7, 79 15, 48
Gender 185



    Female
100 (54.1%) 64 (50.8%) 30 (57.7%) 6 (85.7%)
    Male
85 (45.9%) 62 (49.2%) 22 (42.3%) 1 (14.3%)
Race 185



    White
126 (68.1%) 126 (100.0%) 0 (0%) 0 (0%)
    Black or African American
52 (28.1%) 0 (0%) 52 (100.0%) 0 (0%)
    American Indian or Alaska Native
2 (1.08%) 0 (0%) 0 (0%) 2 (28.6%)
    Native Hawaiian or Other Pacific Islander
1 (0.54%) 0 (0%) 0 (0%) 1 (14.3%)
    Middle Eastern
3 (1.62%) 0 (0%) 0 (0%) 3 (42.9%)
    Race not mentioned
0 (0%) 0 (0%) 0 (0%) 0 (0%)
    Mixed race
1 (0.54%) 0 (0%) 0 (0%) 1 (14.3%)
Insurance type 185



    Medicare
38 (20.5%) 30 (23.8%) 8 (15.4%) 0 (0%)
    Medicaid
30 (16.2%) 13 (10.3%) 16 (30.8%) 1 (14.3%)
    Tricare
6 (3.24%) 1 (0.79%) 4 (7.69%) 1 (14.3%)
    Commercial
103 (55.7%) 75 (59.5%) 23 (44.2%) 5 (71.4%)
    Medicare/Medicaid
1 (0.54%) 1 (0.79%) 0 (0%) 0 (0%)
    Commercial/Medicaid
4 (2.16%) 4 (3.17%) 0 (0%) 0 (0%)
    None
2 (1.08%) 1 (0.79%) 1 (1.92%) 0 (0%)
    Other
1 (0.54%) 1 (0.79%) 0 (0%) 0 (0%)
Smoking status 185



    Never smoker/Never exposure or Unknown
111 (60.0%) 72 (57.1%) 32 (61.5%) 7 (100.0%)
    Exposure
17 (9.19%) 10 (7.94%) 7 (13.5%) 0 (0%)
    Previous
39 (21.1%) 32 (25.4%) 7 (13.5%) 0 (0%)
    Current
18 (9.73%) 12 (9.52%) 6 (11.5%) 0 (0%)
Diagnosis 185



    Moderate-persistent asthma
96 (51.9%) 66 (52.4%) 25 (48.1%) 5 (71.4%)
    Severe-persistent asthma
89 (48.1%) 60 (47.6%) 27 (51.9%) 2 (28.6%)
Medication 185



    Dupixent
152 (82.2%) 99 (78.6%) 47 (90.4%) 6 (85.7%)
    Nucala
20 (10.8%) 17 (13.5%) 2 (3.85%) 1 (14.3%)
    Fasenra
6 (3.24%) 5 (3.97%) 1 (1.92%) 0 (0%)
    Xolair
7 (3.78%) 5 (3.97%) 2 (3.85%) 0 (0%)
1 n (%)

5.2 FEV1 Percent Predicted

Characteristic N = 431
FEV pp at follow-up
    Mean (SD) 77 (24)
    Median (IQR) 78 (64, 94)
    Range 21, 128
FEV pp at baseline
    Mean (SD) 70 (24)
    Median (IQR) 74 (57, 85)
    Range 21, 118
Race
    White 26 (60.5%)
    Black or African American + Other 17 (39.5%)
Smoking
    Never smoker/Never exposure or Unknown 27 (62.8%)
    Exposure 6 (14.0%)
    Previous 6 (14.0%)
    Current 4 (9.30%)
1 n (%)
Table 5.1: Table 5.2: MLR Model Summary for FEV1 Percent Predicted at follow-up
Estimate P-value
FEV1 pp at baseline 0.65 0.00
Black or African American + Other 2.04 0.71
Smoking (Reference: Never smoker/Never exposure or Unknown)
Exposure -7.01 0.35
Previous -14.89 0.06
Current -16.50 0.09
Table 5.3: Table 5.4: Results of bulk tests for factor variables
Degrees of freedom F statistic P-value
Smoking 3 1.94 0.14
Characteristic White, N = 26 Black or African American + Other, N = 17 p-value1
FEV1 percent predicted at baseline

0.2
    Mean (SD) 73 (25) 65 (24)
    Median (IQR) 74 (57, 87) 63 (54, 79)
    Range 21, 118 26, 112
FEV1 percent predicted at follow-up

0.6
    Mean (SD) 77 (25) 77 (24)
    Median (IQR) 82 (70, 93) 72 (63, 95)
    Range 21, 123 41, 128
Absolute change in FEV1 percent predicted from baseline to follow-up

0.7
    Mean (SD) 5 (12) 12 (25)
    Median (IQR) 3 (-2, 10) 4 (-1, 20)
    Range -28, 29 -26, 65
Percent change in FEV1 percent predicted from baseline to follow-up

0.6
    Mean (SD) 8 (16) 32 (66)
    Median (IQR) 3 (-2, 16) 6 (-2, 48)
    Range -26, 40 -27, 246
1 Wilcoxon rank sum exact test

6 Implementation Follow Up Analysis

Characteristic Gap > 14 days, N = 521 No gap > 14 days, N = 1051
Age at first fill

    Mean (SD) 37 (18) 44 (21)
    Median (IQR) 40 (18, 53) 48 (23, 60)
    Range 7, 67 6, 80
Race

    White 29 (55.8%) 75 (71.4%)
    Black or African American + Other 23 (44.2%) 30 (28.6%)
Insurance type

    Commercial 34 (65.4%) 60 (57.1%)
    Medicaid 12 (23.1%) 17 (16.2%)
    Medicare 4 (7.69%) 22 (21.0%)
    Tricare/Other/None 2 (3.85%) 6 (5.71%)
1 n (%)