Clinical characteristics of complete responders versus non-complete responders to omalizumab, benralizumab and mepolizumab in patients with severe asthma: a long-term retrospective analysis

Figures & data

Table 1. Baseline data of the overall study population and according to biological agent.

Variables	All patients (n = 90)	Biological agent			p value
		Omalizumab (n = 44)	Benralizumab (n = 24)	Mepolizumab (n = 22)
Women, n (%)	66 (73.3)	31 (70.5)	16 (66.7)	19 (86.4	.267
Age, years, mean (SD)	55.3 (15.0)	49.5 (20.0)	63.8 (11.0)	58.1 (12.5)	.001
Age at diagnosis, years, mean (SD)	50.7 (16.5)	42.4 (16.4)	61.3 (11.2)	55.9 (11.8)	<.001
Duration of treatment, months, mean (SD)	55 (49.3)	86.6 (53.2)	22.1 (11.4)	27.7 (16.1)	<.001
Obesity, BMI ≥ 30 kg/m^2, n (%)	6 (6.7)	2 (4.5)	4 (16.7)	0	.057
Never smokers, n (%)	68 (75.6)	11 (25.0)	6 (25.0)	5 (22.7)	.856
Rhinosinusitis, n (%)	25 (27.8)	15 (34.1)	3 (12.5)	7 (31.8)	.146
Nasal polyposis, n (%)	23 (25.6)	10 (22.7)	6 (25.0)	7 (31.8)	.725
Bronchiectasis, n (%)	19 (21.1)	9 (20.5)	4 (16.7)	6 (27.3)	.671
Anxiety, n (%)	21 (23.3)	10 (22.7)	6 (25.0)	5 (22.7)	.970
Food allergy, n (%)	10 (11.1)	8 (18.2)	1 (4.2)	0	.036
Atopic dermatitis, n (%)	3 (3.3)	2 (4.5)	1 (4.2)	0	.603
Family history of atopy, n (%)	59 (65.6)	42 (95.5)	11 (45.8)	6 (27.3)	<.001
Gastroesophageal reflux disease, n (%)	13 (14.4)	4 (9.1)	3 (12.5)	6 (27.3)	.134
Obstructive sleep apnea, n (%)	12 (13.3)	5 (11.4)	5 (20.8)	2 (9.1)	.436
Aspirin-exacerbated respiratory disease, n (%)	10 (11.1)	4 (9.1)	3 (12.5)	3 (13.6)	.831
Eosinophilic granulomatosis with polyangiitis, n (%)	5 (5.5)	0	2 (8.3)	3 (13.6)	.058
Allergic bronchopulmonary aspergillosis, n (%)	5 (5.5)	4 (9.1)	1 (4.2)	0	.351
Blood eosinophil count, cells/µL, mean (SD)	607 (1058)	669 (1507)	596 (404)	506 (404)	.845
FeNO, ppb, mean (SD)	48.5 (46.2)	44.6 (45.0)	48.1 (58.0)	56.6 (31.0)	.721
Total serum IgE, kU/L, mean (SD)	495 (724)	713 (899)	329 (419)	239 (401)	.026
Systemic oral corticosteroids, mg, mean (SD)	2.39 (8.5)	1.30 (6.1)	4.59 (13.0)	2.27 (5.0)	.329
Systemic oral corticosteroids, n (%)	16 (17.8)	4 (9.1)	6 (25.0)	6 (27.3)	.106
Exacerbations in the previous year, mean (SD)	3.43 (2.63)	3.75 (3.1)	3.25 (1.98)	3 (2.2)	.513
ACT score, mean (SD)	14.4 (5.4)	12.4 (4.9)	17 (5.2)	14.4 (5.3)	.001
FVC, %, mean (SD)	77.6 (17)	75.7 (17)	74.7 (15.5)	84.1 (31)	.129
FEV1, L, mean (SD)	1.96 (0.76)	2.17 (0.91)	1.68 (0.54)	1.90 (0.51)	.039
FEV1, %, mean (SD)	67.1 (25.6)	66.6 (23.5)	63.1 (20.7)	72.4 (18.3)	.346
Biologic switch, n (%)	10 (11.1)	1 (2.3)	5 (20.8)	4 (18.2)	.013

SD: standard deviation; BMI: body mass index; FeNO: fractional exhaled nitric oxide; ACT: Asthma Control Test; FVC: forced vital capacity; FVE₁: forced expiratory volume in one second.

Table 2. Clinical response at 12 months of follow-up.

Variables	All study patients (n = 87)			Omalizumab (n = 44)			Benralizumab (n = 22)			Mepolizumab (n = 21)
	Baseline	12 months	p value	Baseline	12 months	p value	Baseline	12 months	p value	Baseline	12 months	p value
Blood eosinophils, cells/µL, mean (SD)	648 (1126)	132 (179)	<.001	735 (1625)	236 (214)	.078	628 (416)	48 (22)	<.001	506 (248)	83 (69)	<.001
FeNO, ppb, mean (SD)	49 (47)	36 (36)	.040	44 (45)	36 (44)	.387	53 (61)	29 (32)	.176	57 (33)	43 (24)	.122
FVC, %, mean (SD)	77 (18)	88 (14)	<.001	75.7 (7.3)	85.7 (17)	<.001	74 (16.5)	89.2 (12)	<.001	81.8 (19)	91.7 (14)	<.001
FEV1, %, mean (SD)	66.6 (22)	77.5 (19)	<.001	66.7 (23.5)	76 (19)	<.001	61 (20)	76-7 (19)	<.001	69.5 (18)	79.6 (18)	<.001
FEV1, L, mean (SD)	1.97 (0.78)	2.23 (0.78)	<.001	2.17 (0.9)	2.39 (0.86)	.001	1.67 (0.6)	2.08 (0.7)	.004	1.81 (0.49)	2.04 (0.5)	.012
FEV1 < 80% predicted, % patients	74.4	53.8	<.001	70	57.5	.180	89.5	68.4	.125	68.4	31.6	.016
Exacerbations over 1 year, mean (SD)	3.4 (2.6)	0.29 (0.87)	<.001	3.75 (3.1)	0.23 (0.57)	<.001	3.09 (1.9)	0.36 (0.85)	<.001	3.05 (2.27)	0.33 (0.73)	<.001
No exacerbations, % patients	16.1	82.8	<.001	15.9	84.1	<.001	13.6	81.8	< .001	19	81	<.001
OCS, mg/day, mean (SD)	2.47 (8.6)	0.26 (0.96)	<.001	1.3 (6.2)	0.14 (0.67)	.219	5.02 (14)	0.12 (0.55)	.131	2.38 (5)	0.67 (1.6)	.059
OCS, % patients	18.4	6.9	.006	9.1	4.5	.625	27.3	4.5	.063	28.6	14.3	.250
ACT score, mean (SD)	13.9 (5.3)	21.7 (4.7)	<.001	12.3 (5.0)	21.3 (5)	<.001	16.7 (5)	22.1 (4.3)	.006	13.9 (5)	21.9 (4.6)	<.001
ACT score >20, % patients	17.2	73.4	<.001	7.1	75	<.001	33.3	72.2	.016	16.7	72.2	.002

SD: standard deviation; FeNO: fractional exhaled nitric oxide; FVC: forced vital capacity; FEV₁: forced expiratory volume in one second; OCS: oral corticosteroids; ACT: Asthma Control Test.

Table 3. Complete response (FEV₁ > 80%) at 12 months of follow-up (visit 2) and related factors.

Variables	All study patients (n = 79)			Omalizumab (n = 41)			Benralizumab (n = 19)			Mepolizumab (n = 19)
	Non-responders	Responders	p value	Non-responders	Responders	p value	Non-responders	Responders	p value	Non-responders	Responders	p value
Blood eosinophils, cells/µL, mean (SD)	664 (1147)	293 (262)	.001	713 (1647)	270 (319)	.058	670 (372)	150 (212)	.044	530 (266)	390 (125)	.371
FeNO, ppb, mean (SD)	52 (49)	49 (41)	.892	47.6 (47)	46.9 (50)	.617	55.3 (62)	13 (13)	.232	54.3 (33)	58.3 (12)	.624
FVC, %, mean (SD)	74.9 (18)	83.2 (17)	.060	73.3 (18)	83.5 (14)	.090	74.4 (15)	79.5 (33)	.894	78.8 (19)	88.3 (18)	.357
FEV1, %, mean (SD)	63.5 (21)	73.5 (21)	.064	64.3 (25)	74.1 (20)	.219	61.3 (19)	58 (38)	1	63.9 (16))	81. 7(17)	.035
FEV1, L, mean (SD)	1.81 (0.66)	2.35 (0.97)	.028	1.97 (0.77)	2.73 (1.1)	.033	1.65 (0.59)	1.58 (0.4)	.690	1.66 (0.38)	2.11 (0.57)	.075
Exacerbations over 1 year, mean (SD)	3.4 (2.7)	3.6 (2.7)	.802	3.9 (3.3)	3.6 (2.9)	.890	3.4 (1.8)	3 (1.4)	.733	2.5 (1.9)	3.9 (2.8)	.081
No exacerbations, % patients	16.1	13	.733	18.5	14.3	.733	5.9	0	.725	30.8	0	.126
OCS, mg/day, mean (SD)	2.37 (7.2)	3.22 (12.6)	.523	2.11 (7.8)	0	.135	2.3 (9.4)	30 (42)	.210	3.54 (6.2)	0.67 (1.6)	.416
OCS, % patients	21.4	13	.388	14.8	0	.130	23.5	50	.421	38.5	16.7	.342
ACT score, mean (SD)	14.4 (5.7)	13.1 (4.6)	.512	12.5 (5.2)	11.8 (4.8)	.809	16.9 (5.5)	14.5 (6.3)	.502	14.2 (5.6)	14.2 (4.1)	.959
ACT score > 20, % patients	22.2	5.9	.133	10.5	0	.312	40	0	.266	16.7	20	.870
Age, years, mean (SD)	56.6 (15.9)	50.8 (15.3)	.188	51.1 (17)	44.6 (15)	.322	64.6 (11)	64.5 (8)	.947	57.1 (14.1)	60.5 (11.1)	.598
Women, %	76.8	65.2	.290	77.8	57.1	.168	64.7	50	.683	92.3	83.3	.554
Treatment duration, months, mean (SD)	54.2 (48)	61.1 (51.2)	.493	83.5 (54)	83.7 (54)	.891	24.1 (10)	15 (4)	.206	32.9 (17)	24.8 (9.6)	.404
Age at diagnosis, years, mean (SD)	52.1 (16.7)	45.8 (16.6)	.102	44.1 (17)	37.8 (15)	.187	62.6 (12)	63(8)	.894	54.6 (14.3)	58.8 (12.1)	.568
Rhinosinusitis, % patients	23.2	39.1	.152	25.9	42.9	.269	6	50	.054	38.5	33.3	.829
Nasal polyposis, % patients	25	34.8	.378	22.2	28.6	.653	29.4	50	.554	23.1	50	.241
AERD, % patients	14.3	8.7	.497	11.1	7.1	.685	17.6	0	.517	15.4	16.7	.943
EGPA, number/total patients	2/56	3/23	.116	0/27	0/14		1/17	1/2		2/13	1/6	.943
ABPA, number/total patients	3/56	2/23	.580	2/27	2/14	.877	1/17	0/2	1	0/13	0/6	.381
Bronchiectasis, % patients	25	8.7	.101	25.9	7.1	.150	17.6	0	.517	30.8	16.7	.516
Anxiety, % patients	23.2	13	.307	25.9	7.1	.150	23.5	0	.440	23.1	16.7	.750
Obstructive sleep apnea, % patients	12.5	17.4	.568	11.1	14.3	.768	17.6	50	.288	7.7	16.7	.554
Obesity BMI ≥30 kg/m^2, % patients	7.1	4.3	.643	3.7	0	.659	17.6	50	.386	0	0	1
GERD, % patients	12.5	26.1	.139	7.4	14.3	.482	11.8	50	.161	23.1	50	.241
Never-smokers, % patients	73.2	78.3	.764	70.4	78.6	.712	70.6	100	.372	84.6	66.7	.372
Food allergy, % patients	10.7	13	.767	18.5	21.4	.824	5.9	0	.725	0	0	1
Atopic dermatitis, % patients	3.6	4.3	.870	3.7	7.1	.628	5.9	0	.725	0	0	1
Atopia, % patients	62.5	69.6	.551	92.6	100	.296	35.3	0	.310	30.8	33.3	.911
Bologic switch, number/total patients	7/56	1/23	.460	1/27	0/14	.466	3/17	0/2	.517	3/13	1/6	.533
Total serum IgE, kU/L, mean (SD)	482 (791)	474 (590)	.410	847 (1160)	555 (600)	.163	308 (290)	176 (318)	.081	281 (502)	182 (152)	.726

SD: standard deviation; FeNO: fractional exhaled nitric oxide; FVC: forced vital capacity; FEV₁: forced expiratory volume in one second; OCS: oral corticosteroids; ACT: Asthma Control Test; AERD: aspirin-exacerbated respiratory disease; EGPA: eosinophilic granulomatosis with polyangiitis; ABPA: allergic bronchopulmonary aspergillosis; GERD: gastroesophageal reflux disease.

Table 4. Clinical response at the end of follow-up.

Variables	All study patients (n = 90)			Omalizumab (n = 44)			Benralizumab (n = 24)			Mepolizumab (n = 22)
	Baseline	End of follow-up	p value	Baseline	End of follow-up	p value	Baseline	End of follow-up	p value	Baseline	End of follow-up	p value
Blood eosinophils, cells/µL, mean (SD)	647 (1168)	127 (139)	<.001	733 (1642)	214 (128)	.072	626 (444)	53 (23)	<.001	502 (253)	91.2 (120)	<.001
FeNO, ppb, mean (SD)	49 (47)	33 (33)	.012	44.4 (46)	25.8 (29)	.005	50.6 (58)	36.5 (43)	.448	58 (33)	42 (19)	.091
FVC, %, mean (SD)	77.5 (17)	89.6 (15)	<.001	75.7 (17)	89.3 (13)	<.001	74.3 (16)	91.8 (18)	<.001	84.5 (18.5)	87.5 (16)	.300
FEV1, %, mean (SD)	66.7 (22)	77.2 (20)	<.001	66.6 (23)	78.8 (18.9)	<.001	62.3 (21)	78.1 (22)	<.001	71.8 (18.5)	73.2 (21)	.627
FEV1, L, mean (SD)	1.95 (0.77)	2.18 (0.85)	<.001	2.17 (0.91)	2.41 (0.96)	<.001	1.68 (0.54)	2.1 (0.7)	.001	1.78 (0.47)	1.80 (0.80)	.903
FEV1 < 80% predicted, % patients	72.8	50.6	<.001	70	50	.021	86.4	59.1	.031	63.2	42.1	.125
Exacerbations over 1 year, mean (SD)	3.43 (2.6)	0.33 (0.79)	<.001	3.75 (3.1)	0.39 (0.89)	<.001	3.25 (1.98)	0.25 (0.73)	<.001	3 (2.2)	0.32 (0.6)	<.001
No exacerbations, % patients	15.6	81.1	<.001	15.9	79.5	.008	12.5	87.5	<.001	18.2	77.3	.001
OCS, mg/day, mean (SD)	2.39 (8.5)	0.12 (0.6)	.014	1.3 (6)	0.14 (0.67)	.219	4.59 (14)	0.11 (0.5)	.131	2.27 (4.9)	0.09 (0.4)	.054
OCS, % patients	17.8	4.4	.002	9.1	4.5	.625	25	4.2	.063	27.3	4.5	.063
ACT score, mean (SD)	14.4 (5.4)	21.8 (4.8)	<.001	12.4 (5)	21.4 (5)	<.001	17.1 (5)	21.9 (5)	.002	14.4 (5)	22.3 (4)	<.001
ACT score > 20, % patients	19.4	73.1	<.001	7.1	71.4	<.001	35	75	.008	21.1	73.7	.006

SD: standard deviation; FeNO: fractional exhaled nitric oxide; FVC: forced vital capacity; FEV₁: forced expiratory volume in one second; OCS: oral corticosteroids; ACT: Asthma Control Test.

Table 5. Complete response (FEV₁ > 80%) at the end of follow-up and related factors.

Variables	All study patients (n = 85)			Omalizumab (n = 43)			Benralizumab (n = 23)			Mepolizumab (n = 19)
	Non-responders	Responders	p value	Non-responders	Responders	p value	Non-responders	Responders	p value	Non-responders	Responders	p value
Blood eosinophils, cells/µL, mean (SD)	640 (1168)	376 (272)	.165	657 (1564)	299 (354)	.124	644 (466)	529 (243)	.788	577 (259)	353 (132)	.080
FeNO, ppb, mean (SD)	51.5 (54)	47.4 (32)	.586	49.2 (511)	38.3 (32)	.962	49.5 (69)	52.7 (32)	.190	61.3 (32.3)	54.4 (34)	.902
FVC, %, mean (SD)	73.7 (18)	85.5 (15)	.003	73.6 (18.5)	82.1 (13.5)	.128	71.5 (15)	83.4 (16)	.240	77.9 (20)	90.4 (15)	.156
FEV1, %, mean (SD)	60.3 (21)	79.6 (18)	.000	61.8 (24)	79.9 (17)	.012	57.4 (17)	75.7 (25)	.124	60.4 (15)	82.1 (15)	.006
FEV1, L, mean (SD)	1.74 (0.6)	2.3 1 (0.9)	.004	1.88 (0.70)	3.03 (0.97)	.001	1.58 (0.57)	1.81 (0.45)	.385	1.57 (0.25)	1.95 (0.54)	.146
Exacerbations over 1 year, mean (SD)	3.78 (2.6)	3.07 (2.6)	.234	4.0 (3)	3.44 (3.4)	.348	4 (1.8)	2(1.3)	.012	2.6 (2)	3.60 (2.4)	.356
No exacerbations, % patients	12.7	16.7	.618	13.3	23.1	.427	6.3	14.3	.529	22.2	10	.466
OCS, mg/day, mean (SD)	3.55 (11)	0.7 (1.9)	.064	1.9 (7.4)	0	.172	6.4 (17)	1.9 (3)	.737	4.7 (7.1)	0.8 (1.69)	.315
OCS, % patients	21.8	13.3	.339	13.3	0	.167	25	28.6	.858	44.4	20	.252
ACT score, mean (SD)	14.8 (5.6)	13.7 (5.1)	.435	13.1 (5.2)	10.9 (4.3)	.295	16.4 (6)	17.7 (2.8)	.741	16.4 (5)	13.8 (5.6)	.542
ACT score > 20, % patients	21.4	16.7	.640	10	0	.326	35.7	33.3	.919	25	22.2	.893
Age, years, mean (SD)	55.3 (16)	55.2 (15)	.984	51.5 (17)	44 (15)	.243	63.1 (13)	65 (5.6)	.815	54. 1(14)	63 (11)	.156
Women, %	76.4	73.3	.757	80	46.2	.026	56.3	100	.036	100	90	.330
Treatment duration, months, mean (SD)	57.5 (48)	52 (51)	.624	83.1 (50.7)	88.7 (58)	.751	19.8 (8.9)	29 (14.5)	.082	39 (17)	20.5 (10)	.050
Age at diagnosis, years, mean (SD)	50.5 (17)	51 (17)	.896	44.5 (17)	36.5 (15)	.193	61.4 (13)	63 (6)	.814	51 (14)	61.4 (11)	.094
Rhinosinusitis, % patients	29.1	26.7	.812	33.3	38.5	.746	12.5	0	.328	44.4	30	.511
Nasal polyposis, % patients	16.4	40	.016	20	30.8	.443	12.5	57.1	.025	11.1	40	.153
AERD, % patients	7.3	20	.082	10	7.7	.811	0	42.9	.005	11.1	20	.596
EGPA, number/total patients	57.5 (48)	52 (51)	.624	83.1 (50.7)	88.7 (58)	.751	19.8 (8.9)	29 (14.5)	.082	39 (17)	20.5 (10)	.050
ABPA, number/total patients	2/55	4/30	.095	2/30	2/13	.366	0/10	2/13	.729	0/9	0/10	1
Bronchiectasis, % patients	27.3	10	.063	30	0	.026	12.5	28.6	.349	44.4	10	.089
Anxiety, % patients	23.6	20	.701	23.3	15.4	.556	18.8	28.6	.599	33.3	20	.510
Obstructive sleep apnea, % patients	9.1	23.3	.072	6.7	23.1	.123	12.5	42.9	.104	11.1	10	.937
Obesity BMI ≥30 kg/m^2, % patients	3.6	10	.233	0	7.7	.124	12.5	28.6	.349	0/9	0/10	1
GERD, % patients	9.1	26.7	.031	6.7	15.4	.366	6.3	28.6	.144	22.2	40	.405
Never-smokers, % patients	70.9	80	.513	73.3	76.9	.799	62.5	100	.059	77.8	70	.622
Food allergy, % patients	9.1	13.3	.544	16.7	23.1	.620	0	14.3	.122	0/9	0/10	1
Atopic dermatitis, % patients	3.6	3.3	.942	6.7	0	.340	0	14.3	.122	0	0	1
Atopia, % patients	69.1	63.3	.589	93.3	100	.340	43.8	42.9	.968	33.3	30	.876
Bologic switch, number/total patients	4/55	4/30	.492	1/30	0/13	.505	2/16	2/7	.349	1/9	2/10	.622
Total serum IgE, kU/L, mean (SD)	556 (884)	384 (419)	.591	685 (1093)	708 (527)	.303	259 (266)	521 (717)	.882	382 (583)	138 (140)	.270

SD: standard deviation; FeNO: fractional exhaled nitric oxide; FVC: forced vital capacity; FEV₁: forced expiratory volume in one second; OCS: oral corticosteroids; ACT: Asthma Control Test; AERD: aspirin-exacerbated respiratory disease; EGPA: eosinophilic granulomatosis with polyangiitis; ABPA: allergic bronchopulmonary aspergillosis; GERD: gastroesophageal reflux disease.

Figure 1. Percentages of severe asthma patients with complete response to treatment with biologics. SEPAR criteria: no exacerbations, no use of corticosteroids, ACT score >20, and an FEV₁ >80% predicted (SEPAR: Spanish Society of Pneumology and Thoracic Surgery [15]).

Table 6. Causes of non-response to treatment with biologics in patients with severe asthma.

Variables	All patients (n = 90)			Omalizumab (n = 44)			Benralizumab (n = 24)			Mepolizumab (n = 22)
	Baseline	12 months	End of follow-up	Baseline	12 months	End of follow-up	Baseline	12 months	End of follow-up	Baseline	12 months	End of follow-up
FEV1 < 80% predicted, %	72.1	32.5	34.5	70	32.6	32.6	87.5	38.9	31.8	59.1	26.3	42
Exacerbations ≥ 1, %	83.9	17.2	18.9	84.1	15.9	20.5	86.4	18.2	12.5	81	19	18.2
ACT score < 20, %	73.4	26.6	26.9	92.9	25	28.6	66.7	27.8	25	83.3	28.6	26.3
mOCS, %	18.4	6.9	4.4	9.1	4.5	4.5	27.3	4.5	4.2	28.6	14.3	4.5

FEV₁: forced expiratory volume in one second; ACT: Asthma Control Test; mOCS: maintenance with oral corticosteroids. Data as percentage of patients.

Riccardi E, Guida G, Garino S, et al. “Head-to-head” comparison between biologics in severe asthma: a real-world study. Eur Respir J. 2023; 62:PA4739. doi: 10.1183/13993003.congress-2023.PA4739.

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Data availability statement

Study data are available from the authors (M.B. and C.M.) upon request.