Asthma Symptom Improvements with Benralizumab are Associated with Improvements in Activity Function and Quality of Life for Patients with Severe, Uncontrolled Asthma

Introduction:

Benralizumab is a humanized, anti-eosinophilic monoclonal antibody that improves exacerbations and daily symptoms in patients (pts) with severe, uncontrolled eosinophilic asthma. This study investigated the association of asthma symptom improvements with activity impairment assessments and quality of life (QOL).

Methods:

Analysis of pooled data for adult pts with severe asthma receiving high-dosage ICS/LABA in the Phase III SIROCCO (Lancet. 2016;388:2115 – 27) and CALIMA (Lancet. 2016;388:2128 – 41) trials. Pts received benralizumab (n = 1,474 total) or placebo (n = 742). Daily asthma symptoms; daily activity function (activity limitations, activity avoidance, need to pace oneself during activities); feeling stress; feeling tired; rescue medication use; night-time awakenings; Asthma Control Questionnaire 6 (ACQ-6); and Standardized Asthma QOL Questionnaire for pts ≥12yrs (AQLQ[S]+12) were captured with an electronic diary. Spearman's rank correlation coefficient was used to assess daily asthma symptoms association with diary items and FEV₁ at baseline and end of treatment. Associations of < 0.2, 0.2–< 0.4, 0.4–< 0.6, 0.6–< 0.8, and 0.8 – 1.0 were considered “very weak,” “weak,” “moderate,” “strong,” and “very strong,” respectively.

Results:

Associations were observed between asthma symptoms and daily activity function items, daily stress, ACQ-6, AQLQ(S)+12 overall and domain scores, and FEV₁ in both benralizumab and placebo arms (table). Strong correlations were observed between daily symptoms and daily assessments of activity function items (r = 0.66 – 0.77), feeling tired (r = 0.66 – 0.76), and ACQ-6 scores (r = 0.58 – 0.68) at baseline and change from baseline to end of treatment. Moderate correlations were observed between symptom scores and feeling stressed (r = 0.36 – 0.50); rescue medication use (r = 0.49 – 0.57); and AQLQ(S)+12 domains: overall, symptoms, activity limitation, and emotional domains (r = –0.41 to –0.62). Benralizumab-treated pts had a better correlation between symptom improvement and FEV₁ improvement compared with placebo (r = –0.21 vs. –0.13).

Tab. 1:

Spearman's Rho Correlation Between Asthma-Related Symptoms and Other Patient-reported Outcomes and FEV₁ at Baseline and End of Treatment

Variables For Correlation	Baseline		Change From Baseline to End of Treatment
	Benralizumab	Placebo	Benralizumab	Placebo
Daily diary assessments
Activity function: limitation of activities	0.77	0.76	0.73	0.66
Activity function: avoidance of activities	0.76	0.73	0.72	0.67
Activity function: need to pace self	0.76	0.72	0.71	0.66
Feeling tired	0.76	0.72	0.70	0.66
Feeling stressed	0.50	0.48	0.49	0.36
Percentage of night-time awakening	0.65	0.62	0.48	0.45
Total rescue medication use (puffs per day)	0.57	0.56	0.51	0.49
ACO-6 score	0.68	0.68	0.64	0.58
AQLQ(S)+12
Overall	-0.60	-0.55	-0.61	-0.52
Symptoms	-0.62	-0.59	-0.61	-0.53
Activity limitation	-0.54	-0.50	-0.55	-0.48
Emotional function	-0.47	-0.44	-0.54	-0.41
Environmental stimulation	-0.37	-0.33	-0.42	-0.35
Prebronchodilator FEV1 (L)	-0.09	-0.08	-0.21	-0.13
ACQ-6, Asthma Control Questionnaire 6; AQLQ(S)+12, Standardized Asthma Quality of Life Questionnaire for patients 12 years and older; FEV1, forced expiratory volume in 1 second. All p< 0.05.

Conclusions:

Asthma-related symptoms and improvements are associated with other important aspects of improvement in patient well-being, especially in those with severe, uncontrolled asthma receiving optimal care.