Dupilumab Efficacy in Patients Stratified by Baseline Treatment Intensity and Lung Function

Figures & data

Table 1 Baseline Demographic and Clinical Characteristics by Baseline ICS Dose and FEV₁% Predicted – ITT Population

Characteristics	Medium ICS Dose and FEV1% Predicted 60–90%				High ICS Dose and FEV1% Predicted <60%
	1.14 mL/200 mg q2w		2 mL/300 mg q2w		1.14 mL/200 mg q2w		2 mL/300 mg q2w
	Placebo (n = 75)	Dupilumab (n = 180)	Placebo (n = 91)	Dupilumab (n = 171)	Placebo (n = 80)	Dupilumab (n = 176)	Placebo (n = 93)	Dupilumab (n = 171)
Age, mean (SD), years	42.7 (18.3)	44.0 (17.1)	43.8 (16.7)	43.5 (16.7)	49.9 (13.7)	51.5 (13.1)	50.3 (13.8)	50.6 (14.1)
Female, n (%)	43 (57.3)	105 (58.3)	65 (71.4)	105 (61.4)	45 (56.3)	99 (56.3)	56 (60.2)	108 (63.2)
Height, mean (SD), cm	165.4 (10.5)	166.9 (10.0)	165.2 (9.4)	165.3 (10.0)	165.4 (9.3)	165.5 (9.4)	165.9 (11.2)	164.1 (9.6)
BMI, mean (SD), kg/m^2	26.9 (5.8)	28.2 (6.6)	28.2 (6.9)	28.1 (7.2)	31.1 (6.8)	29.4 (5.8)	30.1 (6.5)	29.8 (6.6)
Pre-bronchodilator FEV1, mean (SD), L	2.2 (0.6)	2.2 (0.6)	2.1 (0.5)	2.2 (0.5)	1.4 (0.5)	1.4 (0.5)	1.4 (0.4)	1.4 (0.5)
Pre-bronchodilator FEV1, mean (SD), % predicted	69.5 (6.2)	69.3 (6.2)	69.8 (6.4)	69.4 (6.1)	46.9 (9.1)	46.6 (9.2)	46.5 (8.3)	45.5 (10.3)
FEV1 reversibility, mean (SD), %	21.9 (13.7)	22.7 (18.2)	23.2 (16.7)	20.5 (16.2)	26.3 (16.0)	32.2 (25.6)	29.7 (16.5)	34.5 (32.8)
Severe asthma exacerbations in past year, mean (SD), n	1.7 (1.0)	1.8 (3.8)	1.9 (1.7)	1.8 (2.1)	2.4 (2.0)	2.1 (2.1)	2.7 (2.5)	2.2 (1.5)
ACQ-5 score, mean (SD)	2.6 (0.6)	2.5 (0.6)	2.6 (0.6)	2.6 (0.7)	2.9 (0.8)	2.9 (0.9)	2.9 (0.8)	3.0 (0.8)
AQLQ score, mean (SD)	4.5 (1.0)	4.6 (1.0)	4.7 (0.9)	4.5 (1.0)	4.0 (1.1)	4.3 (1.1)	4.1 (1.0)	4.0 (1.1)
Blood eosinophil count, median (IQR), cells/µL	260 (130–440)	240 (120–440)	210 (120–410)	230 (130–450)	305 (165–600)	250 (140–470)	360 (180–540)	290 (130–500)
FeNO, median (IQR), ppb	26 (16–56)	25 (17–43)	27.50 (18–51)	24 (13–40)	23 (13–38)	24 (12–43)	30 (15.5–51.5)	25 (15–41)
Serum total IgE, median (IQR), IU/mL	182 (81–493)	153 (65–378)	205 (53–496)	178 (67–546)	225 (54–564)	147 (49–504)	162 (77–319)	192 (71–436)

Abbreviations: ACQ-5, 5-item Asthma Control Questionnaire; AQLQ, Asthma Quality of Life Questionnaire; BMI, body mass index; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; ITT, intent-to-treat; IQR, interquartile range; ppb, parts per billion; q2w, every 2 weeks; SD, standard deviation.

Figure 1 Annualized rate of severe exacerbations over the 52-week treatment period in patients with (A) medium-dose ICS and FEV₁% predicted ≥60–90% and ≥150 eosinophils/µL, (B) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL, (C) medium-dose ICS and FEV₁% predicted ≥60–90% and ≥150 eosinophils/µL or ≥25 ppb FeNO, and (D) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL or ≥25 ppb FeNO at baseline – ITT population. ***P<0.001; **P<0.01; *P<0.05 vs matched volume placebo.

Abbreviations: CI, confidence interval; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; ITT, intent-to-treat; LS, least squares; ppb, parts per billion; q2w, every 2 weeks.

Figure 2 Change from baseline in pre-bronchodilator FEV₁ (L) over the 52-week treatment period in patients with (A) medium-dose ICS and FEV₁% predicted ≥60–90% and ≥150 eosinophils/µL, (B) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL, (C) medium-dose ICS and FEV₁% predicted ≥60–90% and ≥150 eosinophils/µL or ≥25 ppb FeNO, and (D) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL or ≥25 ppb FeNO at baseline – ITT population. ***P<0.001; **P<0.01; *P<0.05 vs matched volume placebo.

Abbreviations: FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; ITT, intent-to-treat; LS, least squares; ppb, parts per billion; q2w, every 2 weeks; SE, standard error.

Figure 3 Change from baseline in ACQ-5 score over the 52-week treatment period in patients with (A) medium-dose ICS and FEV₁% predicted ≥60–90% and ≥150 eosinophils/µL, (B) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL, (C) medium-dose ICS and FEV₁% predicted ≥60–90% and ≥150 eosinophils/µL or ≥25 ppb FeNO, and (D) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL or ≥25 ppb FeNO at baseline – ITT population. ***P<0.001; **P<0.01; *P<0.05 vs matched volume placebo.

Abbreviations: ACQ-5, 5-item Asthma Control Questionnaire; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; ITT, intent-to-treat; LS, least squares; ppb, parts per billion; q2w, every 2 weeks; SE, standard error.

Figure 4 Change from baseline in AQLQ score over 52 weeks in patients with (A) medium-dose ICS and FEV_1% predicted ≥60–90% and ≥150 eosinophils/µL, (B) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL, (C) medium-dose ICS and FEV₁% predicted ≥60–90% and ≥150 eosinophils/µL or ≥25 ppb FeNO, and (D) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL or ≥25 ppb FeNO at baseline – ITT population. **P<0.01; *P<0.05 vs matched volume placebo.

Abbreviations: AQLQ, Asthma Quality of Life Questionnaire; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; ITT, intent-to-treat; LS, least squares; ppb, parts per billion; q2w, every 2 weeks; SE, standard error.

Figure 5 Median FeNO (ppb) during the 52-week treatment period in patients with (A) medium-dose ICS and FEV₁% predicted ≥60–90% and ≥150 eosinophils/µL, (B) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL, (C) medium-dose ICS and FEV₁% predicted ≥60–90% and ≥150 eosinophils/µL or ≥25 ppb FeNO, (D) high-dose ICS and FEV₁% predicted <60% and ≥150 eosinophils/µL or ≥25 ppb FeNO at baseline – exposed population. ***P<0.001; **P<0.01 vs matched volume placebo (P-values based on change from baseline vs placebo).

Abbreviations: CI, confidence interval; FeNO, fractional exhaled nitric oxide; FEV₁, forced expiratory volume in 1 second; ICS, inhaled corticosteroids; ppb, parts per billion; q2w, every 2 weeks; SE, standard error.