Baseline Predictors of Being Exacerbation-Free During 2 Years of Benralizumab Treatment

Introduction: Integrated analyses of Phase III trials are important in characterizing patients who have the greatest long-term benefits with benralizumab.We aimed to examine the relationship between exacerbation frequency during 2 years of benralizumab treatment, baseline characteristics, and efficacy.

Methods: We performed post-hoc subgroup integrated analysis of the 48-week SIROCCO (Lancet 2016;388 : 2115 – 27) and 56-week CALIMA (Lancet 2016;388 : 2128 – 41) studies with the 56-week BORA extension study (Lancet Respir Med 2019;7 : 46 – 59). Patients receiving benralizumab 30 mg subcutaneously every 8 weeks who had baseline blood eosinophil counts ≥ 300 cells/µL were assessed. Patients were evaluated based on number of exacerbations experienced during the 2-year treatment period (0, 1, ≥ 2).

Results: Baseline pre-bronchodilator forced expiratory volume in 1 second (FEV₁;%), pre-bronchodilator FEV₁/forced vital capacity (FVC), and prior requirement for mechanical ventilation were significantly different for patients with 0 vs.1 exacerbations, with additional significant differences for patients with 0 vs. ≥ 2 exacerbations ([Table 1]). Greater improvements in Asthma Control Questionnaire-6 (ACQ-6) and Standardized Asthma Quality of Life Questionnaire for patients 12 years and older (AQLQ(S)+12) scores were observed for patients with 0 vs. 1/≥ 2 exacerbations, while lesser improvement in FEV₁ and ACQ-6 and AQLQ(S)+12 scores was observed for the ≥ 2 exacerbation group vs. the other groups by 16 weeks and was sustained for 2 years.

Table 1 Association of exacerbation frequency during the 2-year benralizumab Q8W treatment with baseline characteristics^a.

	Exacerbations in 2-year period			P-values
	0 (n = 161)	1 (n = 80)	≥ 2 (n = 77)	0 vs. 1	0 vs. ≥ 2
ACQ-6, Asthma Control Questionnaire 6; BD, bronchodilator; ED, emergency department; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; ICU, intensive care unit; PN, predicted normal; Q8W, every 8 weeks (first three doses every 4 weeks); SD, standard deviation. a Pts also received high-dosage inhaled corticosteroids/long-acting β2-agonists. b Means (SD). c n (%). d Missing data.
Pre-BD FEV1 PN [%]b	60 (15)	56 (14)	53 (14)	0.030	< 0.001
Body mass index [kg/m²]b	27 (5)	27 (5)	30 (8)	0.508	0.001
ACQ-6 scoreb	2.6 (0.9)	2.7 (0.7)	3.0 (1.0)	0.328	0.001
Age at asthma diagnosis [years]b	32 (17)	29 (20)	25 (17)	0.235	0.002
≥ 1 exacerbations in the past 12 months leading to ED visitc	16 (10)	10 (13)	18 (23)	0.240	0.002
Post-BD FEV1 PN [%]b,d	73 (18)	70 (19)	66 (19)	0.290	0.006
Time since asthma diagnosis [years]b	17 (13)	20 (14)	22 (14)	0.071	0.006
Previous admission to ICU for asthmac	8 (5)	8 (10)	13 (17)	0.171	0.006
Pre-BD FEV1 (L)b	1.84 (0.65)	1.68 (0.55)	1.61 (0.60)	0.057	0.009
Time since first asthma symptoms started [years]b	20 (14)	22 (15)	25 (14)	0.132	0.010
Post-BD FEV1/FVC [%]b,d	66 (13)	63 (14)	62 (12)	0.081	0.013
Number of exacerbations in the previous 12 monthsc
2	111 (69)	49 (61)	40 (52)	0.249	0.014
≥ 3	50 (31)	31 (39)	37 (48)
Pre-BD FEV1/FVC [%]b	63 (12)	59 (13)	58 (12)	0.020	0.015
Gastroesophageal refluxc	27 (17)	10 (13)	24 (31)	0.451	0.017
Post-BD FEV1 (L)b,d	2.23 (0.81)	2.10 (0.77)	1.98 (0.79)	0.212	0.027
Previously requiring mechanical ventilationc	2 (1)	5 (6)	5 (6)	0.042	0.038
Reversibility [%]b,d	22 (19)	27 (29)	25 (20)	0.153	0.321
≥ 1 exacerbations in the past 12 months leading to hospitalizationc	29 (18)	13 (16)	22 (29)	0.581	0.135

Conclusions: Patients who remained exacerbation-free during 2 years of benralizumab treatment were older at asthma onset, had better lung function, smaller intensive care unit asthma admission rate and body mass index, and less gastroesophageal reflux.