Efficacy of Benralizumab for Patients with Severe, Uncontrolled Atopic Asthma by Serum Immunoglobulin E Concentrations

Introduction:

Patients with severe asthma may have eosinophilia and/or allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody that demonstrated efficacy in severe, uncontrolled eosinophilic asthma. We investigated benralizumab efficacy for patients with severe, uncontrolled atopic asthma with serum IgE concentrations 30 – 700 kU/L. This is similar criteria to that used for patients who qualify for omalizumab treatment.

Methods:

We conducted an analysis of pooled data from two Phase III studies (SIROCCO [Lancet. 2016;388:2115 – 27] and CALIMA [Lancet. 2016;388:2128 – 41]). Patients included adults with severe, uncontrolled asthma with ≥2 exacerbations in the previous year and receiving high-dosage inhaled corticosteroids/long-acting β2-agonists, with or without other controllers. Patients received add-on benralizumab 30 mg every 8 weeks (Q8W; first three doses Q4W) or placebo. At screening, patients tested as atopic and had serum IgE concentrations 30 – 700 kU/L.

Results:

A total of 538 patients met the atopy and IgE criteria (252 placebo and 286 benralizumab Q8W). Benralizumab reduced exacerbations by 37% (95% CI, 20 to 51; p < 0.001) and increased FEV₁ by 81 mL (95% CI, –4 to 166; p = 0.06) vs. placebo. Similar trends were observed for Asthma Control Questionnaire 6 (ACQ-6) improvements. Patient stratification by baseline blood eosinophils (≥300 or < 300 cells/µL) revealed greater efficacy for patients with ≥300 than < 300 cells/µL. Similar efficacy was observed for patients who did not meet the atopy and IgE criteria (table).

Tab. 1:

Effects of Benralizumab QSW on AER and on FEV₁

	Patients who met criteria of having atopya and serum IgE 30 – 700 kU/L		Patients who did not meet criteria of having atopya and serum IgE 30 – 700 kU/L
Baseline blood eosinophil count (cells/µL)	AER reduction [%], mean (95% CI) b	FEV1 change from baseline [mL]. mean (95% CI) c	AER reduction [%], mean (95% CI) b	FEV1 change from baseline [mL], mean (95% CI) c
All patients	37 (20 to51)d	81 (-4 to 166)	38 (24 to 49)d	129 (69 to 190)d
High (≥300)	47 (27 to 62)d	140 (28 to 252)d	41 (25 to 54)d	157 (78 to 235)d
Low (< 300)	27 (-7 to 50)	28 (-101 to 158)	32 (5 to 51)d	85 (-11 to 181)
AER, annual exacerbation rate; CI, confidence interval: FEV1, forced expiratory volume in 1 second; IgE, immunoglobulin E; Q4W, every 4 weeks; QSW, every 8 weeks (Q4W for the first three doses). aBy Phadiatop test. bEstimates were calculated using a negative binomial model, with adjustment for study, treatment, region, oral corticosteroid use at time of randomization, and prior exacerbations. cEstimates were calculated using a mixed-effects model for repeated measures analysis with adjustment for study, treatment, region, oral corticosteroid use at time of randomization, and baseline FEV1. dp ≤0.05 vs. placebo.

Conclusion:

Benralizumab reduced exacerbations and improved lung function for patients with severe, uncontrolled atopic asthma with serum IgE 30 – 700 kU/L. Efficacy was greater for patients with greater vs. lesser blood eosinophil counts.

 

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