Patient-Reported Activity Impairment, Stress, and Tiredness Improvement in Patients with Severe, Uncontrolled Asthma with Eosinophilic Inflammation: Pooled Results from Two Phase III Trials of Benralizumab

Introduction:

Patients with severe, uncontrolled asthma may experience symptoms that impair their ability to engage in activities and increase their perceived feelings of stress and tiredness. We evaluated treatment with the humanized, anti-eosinophilic monoclonal antibody benralizumab on asthma-related activity impairment, stress, and tiredness.

Methods:

This analysis used pooled data for adult patients with severe asthma receiving high-dosage inhaled corticosteroids/long-acting β₂-agonists with baseline blood eosinophil counts ≥300 cells/µL in the Phase III SIROCCO (Lancet. 2016;388:2115 – 27) and CALIMA (Lancet. 2016;388:2128 – 41) trials. Patients received benralizumab 30 mg either every 4 weeks (Q4W, n = 515) or every 8 weeks (Q8W, first three doses Q4W, n = 501) or placebo Q4W (n = 514) to end of treatment (48 or 56 weeks). Patients in these trials completed a daily diary that included items concerning asthma-related activity limitations, the need to pace oneself during activities, activity avoidance, perceived stress, and tiredness. A 5-point categorical response scale was used for each item. Baseline for daily measures was the 10-day period before Week 0 (randomization). Daily assessments were summarized as biweekly means if ≥7 of 14 daily assessments were available. Each outcome measure was compared across treatment arms from baseline to end of treatment for patients in the full pooled data set using repeated-measures analyses, adjusting for baseline value, oral corticosteroid use, and geographic region.

Results:

Patients who received the benralizumab Q8W dosing regimen had statistically significant improvements in all three aspects of activity impairment, stress, and tiredness compared with placebo recipients at end of treatment (table). Compared with patients receiving placebo, patients receiving benralizumab Q4W had statistically significant improvements in activity limitations and pacing, but not in activity avoidance, stress, or tiredness.

Tab. 1:

Daily Stress and Activity' Impairment Assessments: 14-Day Summary Score Change From Baseline to End of Treatment for Two Benralizumab Dosing Regimens vs. Placebo

		Treatment Groups
Daily Assessment	Measures	Benralizumab 30 mg Q4W (n = 515)	Benralizumab 30 mg Q8W (n = 501)	Placebo (n = 514)
Stress	LS mean change	-0.35	-0.41	-0.32
	Difference (95% CI) (vs. placebo)	-0.04 (-0.08, 0.01)	-0.09 (-0.14, -0.04)	-
	P-value	0.158	< 0.001	-
Feeling tired	LS mean change	-0.74	-0.82	-0.67
	Difference (95% CI) (vs. placebo)	-0.07 (-0.17, 0.03)	-0.14 (-0.25, -0.04)	-
	P-value	0.159	0.005	-
Activity limitations	LS mean change	-0.77	-0.83	-0.66
	Difference (95% CI) (vs. placebo)	-0.11 (-0.20, -0.01)	-0.16 (-0.26, -0.07)	-
	P-value	0.025	< 0.001	-
Activity avoidance	IS mean change	-0.78	-0.85	-0.68
	Difference (95% CI) (vs. placebo)	-0.10 (-0.19, 0.00)	-0.16 (-0.26, -0.06)	-
	P-value	0.060	0.001	-
Activity pacing	LS mean change	-0.81	-0.87	-0.68
	Difference (95% CI) (vs. placebo)	-0.13 (-0.23, -0.03)	-0.19 (-0.30, -0.09)	-
	P-value	0.013	< 0.001	-
CI, confidence interval; LS, least squares; Q4W, every 4 weeks; Q8W, every 8 weeks (first three doses Q4W).

Conclusions:

Benralizumab treatment improved patient-reported activity impairment, stress, and tiredness. Results were consistent with previously published findings that benralizumab reduces exacerbations and asthma symptoms and improves asthma-specific health-related quality of life.