Real-World Effectiveness of Dupilumab for Patients with Severe Asthma: A Retrospective Study

Figures & data

Table 1 Patient Characteristics at Baseline (n = 26)

	All Patients (n = 26)	Previous Biologics (-) (n = 10)	Previous Biologics (+) (n = 16)	P value Between Two Groups
Male, n (%)	4 (15)	2 (20)	2 (13)	0.63*
Age (years), mean (SD) (range)	48.9 (12.4) (21–74)	46.9 (13.6) (21–67)	50.1 (11.8) (31–74)	0.83^†
Duration of disease (years), mean (SD) (range)	18.8 (16.7) (1–55)	17.5 (18.3) (3–55)	19.7 (16.2) (1–53)	0.62^†
Body mass index (kg/m^2), mean (SD)	22.7 (5.5)	23.6 (7.8)	22.1 (3.6)	> 0.99^†
Smoking (never/former/current), n	19/6/1	7/2/1	12/4/0	0.43^‡
Allergies (seasonal/perennial/both), n	3/4 /12	1/2/5	2/2/7	0.91^‡
Initial treatments use
–ICS/LABA, n (%)	26 (100)	10 (100)	16 (100)	–
–ICS dose (µg), mean (SD)	948 (279)	920 (229)	966 (311)	0.80^†
–LAMA, n (%)	19 (73)	7 (70)	12 (75)	> 0.99*
–LTRA, n (%)	23 (88)	9 (90)	14 (88)	> 0.99*
–xanthine derivative, n (%)	10 (38)	3 (30)	7 (44)	0.68*
–maintenance therapy of OCS, n (%)	9 (35)	3 (30)	6 (38)	0.42*
–daily dose of OCS (mg), mean (range)	11.6 (1–30) (n = 9)	23.3 (10–30) (n = 3)	5.7 (1–17.5) (n = 6)	0.037^†
Comorbidities
–ECRS, n (%)	17 (65)	5 (50)	12 (75)	0.23*
–EOM, n (%)	5 (19)	1 (10)	4 (25)	0.62*
–AERD, n (%)	10 (38)	3 (30)	7 (44)	0.68*
–EGPA, n (%)	2 (8)	1 (10)	1 (6)	> 0.99*
–atopic dermatitis, n (%)	6 (23)	2 (20)	4 (25)	> 0.99*
–chronic eosinophilic pneumonia, n (%)	1 (4)	0 (0)	1 (6)	> 0.99*
Previous biologics
–omalizumab, n (%)/mean (range) (month)	7 (27)/41.5 (6–134)	–	7 (44)/41.5 (6–134)	–
–mepolizumab, n (%)/mean (range) (month)	10 (38)/21.2 (7–48)	–	10 (63)/21.2 (7–48)	–
–benralizumab, n (%)/mean (range) (month)	5 (19)/5.0 (1–14)	–	5 (31)/5.0 (1–14)	–
Observation period (months), mean (range)	12.6 (1–30)	10.7 (2–25)	13.8 (1–30)	0.37^†

Notes: Data are presented as n (%) or mean (standard deviation), unless otherwise stated. *Fisher’s exact test, ^†Mann–Whitney U-test, ^‡Chi-square test.

Abbreviations: SD, standard deviation; OCS, oral corticosteroids; ECRS, eosinophilic chronic rhinosinusitis; EOM, eosinophilic otitis media; AERD, aspirin-exacerbated respiratory disease; EGPA, eosinophilic granulomatosis with polyangiitis.

Table 2 Change from Baseline to Last Follow-Up in Asthma Patients Who Received Dupilumab Treatment

	All Patients (n = 26)			Previous Biologics (-) (n = 10)			Previous Biologics (+) (n = 16)			p value Between Two Groups at Baseline
	Baseline	Follow Up	p Value	Baseline	Follow Up	p value	Baseline	Follow Up	p value	p value
Peripheral blood eosinophil counts (/µL)	148 (171)	528 (787)	< 0.01	240 (202)	284 (280)	0.37	91 (123)	698 (977)	< 0.01	< 0.05
Peripheral blood basophil counts (/µL)	38 (22)	62 (47)	< 0.01	41 (18)	39 (19)	0.37	36 (25)	77 (54)	< 0.01	0.37
Serum IgE (IU/mL)	181 (238)	65 (84)	< 0.001	163 (305)	20 (28)	0.02	190 (207)	90 (95)	< 0.01	0.73
FeNO (ppb)	39 (34)	19 (10)	< 0.01	33 (30)	20 (11)	0.06	43 (37)	18 (10)	0.03	0.32
%FVC (%)	99.1 (13.7)	100.3 (15.3)	0.75	95.4 (11.0)	93.0 (13.9)	0.61	101.6 (15.0)	104.0 (15.1)	0.53	0.16
%FEV1 (%)	91.1 (16.5)	92.5 (14.6)	0.61	90.8 (17.7)	91.4 (18.8)	0.74	91.3 (16.3)	93.0 (12.9)	0.86	0.70
FEV1/FVC (%)	76.7 (10.9)	77.2 (9.4)	0.20	78.5 (9.6)	81.6 (5.3)	< 0.05	75.5 (11.8)	75.1 (10.4)	0.81	0.62
FEV1 (mL)	2303 (593)	2280 (590)	0.76	2395 (621)	2384 (552)	0.74	2241 (587)	2228 (621)	> 0.99	0.62
%PEF (%)	94.8 (20.8)	99.4 (18.3)	0.65	98.9 (20.4)	102.7 (20.1)	> 0.99	92.1 (21.3)	97.7 (17.9)	0.51	0.41
ACT (pts)	18.2 (5.3)	21.5 (4.3)	< 0.01	16.2 (4.8)	21.0 (4.2)	< 0.05	19.5 (5.3)	21.8 (4.5)	< 0.05	0.08
Number of annual exacerbations	3.4 (4.1)	1.6 (2.7)	< 0.01	4.6 (5.9)	2.0 (4.0)	0.24	2.7 (2.4)	1.3 (1.7)	< 0.01	0.56
Prednisone equivalent dose (mg/day), (n = 9)	11.6 (11.6)	5.3 (6.5)	< 0.05	23.3 (11.5) (n = 3)	8.3 (8.8) (n = 3)	0.11	5.7 (6.0) (n = 6)	3.8 (5.3) (n = 6)	< 0.05	< 0.05

Notes: Data are presented as the mean (standard deviation) and were analyzed using the Wilcoxon signed-rank test. The follow up data was used from six months after initiation except the number of annual exacerbations and prednisolone equivalent dose. These two data was adopted at last follow up.

Abbreviations: FeNO, fractional exhaled nitric oxide; FVC, forced volume capacity; FEV₁, forced expiratory volume in one second; PEF, peak expiratory flow; ACT, Asthma Control Test.

Figure 1 The change in the number of annual exacerbations before and after dupilumab treatment: subgroup analysis. The number of annual exacerbations before and after treatment was analyzed using the Wilcoxon signed-rank test based on the following biomarkers before use of the first biologic: (A) BEC ≥ 150, (B) BEC < 150, (C) BEC ≥ 300, (D) BEC < 300, (E) FeNO ≥ 25, (F) FeNO < 25, (G) IgE ≥ 167, and (H) IgE < 167. We reported the last follow-up data as “after treatment”. T bars represent the 95% confidence intervals.

Table 3 Clinical Efficacy Based on Each Evaluation

	Reduction Rate of AE (n = 20)	Change in ACT From Baseline (n = 26)
Effective, n (%)	13 (65)	16 (62)
No change, n (%)	2 (10)	8 (31)*
Worsening, n (%)	5 (25)	2 (7)

Notes: Data are presented as n (%). The evaluations based on the reduction rate of AE were as follows: effective (≤ −50%), worsening (> 0%) and no change (other). The evaluations based on the change in ACT were as follows: effective (≥ 3), worsening (≤ −3) and no change (other). Of the 26 patients, we excluded six patients who had not experienced any AE. *Of the eight patients, four patients had 25 points in the ACT score without MCID.

Abbreviations: AE, acute exacerbations; ACT, Asthma Control Test; MCID, minimal clinically important difference.

Table 4 Factors Predicting Super Responders According to the Logistic Regression Analysis

	Super-Responders (n = 9)	Odds Ratio (95% CI) (Univariate)	p value	Odds Ratio (95% CI) (Multivariate)	p value
Gender (male), n (%)	1 (11)	0.58 (0.05–6.6)	0.66	–	–
Age (≥ 65 year-old), n (%)	0 (0)	–	0.97	–	–
Duration of disease >20 (years), n (%)	2 (22)	0.52 (0.08–3.4)	0.50	–	–
BMI (≥ 25) (kg/m^2), n (%)	0 (0)	–	0.97	–	–
Smoking status (never), n (%)	7 (78)	1.46 (0.22–9.6)	0.70	–	–
Data prior to previous any biologics
–pre-bio BEC^† (≥ 150) (/µL), n (%)	9 (100)	–	0.97	–	–
–pre-bio BEC^† (≥ 300) (/µL), n (%)	8 (89)	11.4 (1.2–113)	0.037	10.4 (1.02–106)^§	0.048^§
–pre-bio serum IgE level^† (≥ 167) (IU/mL), n (%)	4 (44)	0.62 (0.12–3.2)	0.57	–	–
–pre-bio FeNO^† (≥ 25) (ppb), n (%)	6 (67)	1.75 (0.31–9.8)	0.52	–	–
Data prior to dupilumab administration
–pre-DUP BEC^‡ (≥ 150) (/µL), n (%)	6 (67)	9.3 (1.4–60.2)	0.019	9.8 (1.2–78.7)	0.031
–pre-DUP BEC^‡ (≥ 300) (/µL), n (%)	4 (44)	12.8 (1.1–143)	0.038	–	–
–pre-DUP serum IgE level^‡ (≥ 167) (IU/mL), n (%)	4 (44)	1.76 (0.33–9.5)	0.51	–	–
–pre-DUP FeNO^‡ (≥ 25) (ppb), n (%)	7 (78)	3.9 (0.63–24.7)	0.14	3.7 (0.47–29.4)	0.22
Comorbidities
–with AERD, n (%)	5 (19)	3.0 (0.56–16.1)	0.19	2.4 (0.38–15.8)^§ 3.2 (0.40–26.1)	0.35^§ 0.27
–with atopic dermatitis, n (%)	1 (4)	0.30 (0.03–3.1)	0.31	–	–
–with ECRS, n (%)	9 (35)	–	0.97	–	–
–with GERD, n (%)	2 (8)	0.32 (0.05–2.0)	0.23	–	–

Notes: We performed two patterns of multivariate logistic analysis: analyzed using biomarker prior to treatment of any biologics, and dupilumab. “Super responder” is defined more than two of the following criteria: as exacerbation-free, discontinuation of maintenance of oral corticosteroids, and improvement of the ACT score with three or greater points or ACT >19 after administration of dupilumab. ^†Pre-bio: The data were shown as those before the administration of any biologics. ^‡Pre-DUP: The data were shown as those before the administration of dupilumab. ^§Multivariate logistic analysis for pre-bio data, multivariate logistic analysis for pre dupilumab data.

Abbreviations: CI, confidence interval; ACT, Asthma Control Test; BMI, body mass index; BEC, blood eosinophil counts; FeNO, fractional exhaled nitric oxide; AERD, aspirin-exacerbated respiratory disease; ECRS, eosinophilic chronic rhinosinusitis; GERD, gastro-esophageal reflux disease.

Figure 2 The change in clinical parameters before and after dupilumab treatment. Number of the annual exacerbations: (A) all patients, (B) previous biologics (-) group, and (C) previous biologics (+) group. Change from baseline in ACT score: (D) all patients, (E) previous biologics (-) group, and (F) previous biologics (+) group. Change from baseline in BEC: (G) all patients, (H) previous biologics (-) group, and (I) previous biologics (+) group. All data were analyzed using Wilcoxon signed-rank test. The upper and lower bars represent the standard errors.

Notes: ^†p < 0.05 compared with baseline. ^‡p < 0.01 compared with baseline.

Abbreviations: pre-DUP, pretreatment with dupilumab; BEC, blood eosinophil count; m, month (s); n, number of patients for whom clinical data were available.