Effects of Immunoglobin E Concentration, Eosinophil Concentration, and Atopy Status on Benralizumab Efficacy in Asthma

Introduction:

We investigated the efficacy of the anti-eosinophilic monoclonal antibody benralizumab for patients with severe, uncontrolled asthma by high versus low serum IgE concentrations and atopy status.

Methods:

We analyzed pooled data from two Phase III studies, SIROCCO (Lancet. 2016;388:2115 – 27; 48 weeks [N = 1,204]) and CALIMA (Lancet. 2016;388:2128 – 41; 56 weeks [N = 1,306]). Adult patients with severe, uncontrolled asthma on high-dosage inhaled corticosteroids and long-acting β₂-agonists received benralizumab 30 mg every 8 weeks (Q8W; first three doses Q4W) or placebo. Patients were analyzed into those patients with high vs. low serum IgE (≥150 or < 150 kU/L respectively). Each group was further divided by atopy status (Phadiatop test).

Results:

A total of 765 patients (390 placebo and 375 benralizumab Q8W) had high IgE, and 681 patients (340 placebo and 341 benralizumab Q8W) had low IgE. No correlation between blood eosinophil counts and IgE concentrations was observed in the total group, but a positive relationship was noted for atopic patients. Treatment with benralizumab resulted in 41% and 37% reductions in exacerbation rate (p< 0.05) and 112- and 122-mL FEV₁ increases (p< 0.05) versus placebo for patients with high or low IgE, respectively. Similar efficacy was observed across groups after stratification by atopy status and tended to be greater for patients with blood eosinophils ≥300 cells/µL irrespective of IgE or atopy status (table).

Tab. 1:

Effects of Benralizumab Q8W on AER and FEV₁ by Baseline IgE Concentration, Atopy Status, and Blood Eosinophil Count

IgE concentration (kUVL)	Atopy status by Phadiatop test	Blood eosinophil count (cells/µL)	AER reduction [%], mean (95% CI) a	FEV1 change from baseline [niL], mean (95% CI) b
High (≥150)	All patients	All patients	41 (26 to 52)c	112 (43 to 181)c
Low (< 150)	All patients	All patients	37 (22 to 50)c	122 (54 to 191)c
High (≥150)	All patients	High (≥300)	44 (21 to 57)c	137 (55 to 220)c
Low (< 150)	All patients	High (≥300)	44 (23 to 59)c	139 (44 to 234)c
High (≥150)	All patients	Low (< 300)	28 (-11 to 54)	-4 (-123 to 114)
Low (< 150)	All patients	Low (< 300)	27 (1 to 47)c	101 (5 to 197)c
High (≥150)	Positive	All patients	37 (20 to 51)c	91 (13 to 170)c
Low (< 150)	Positive	All patients	35 (7 to 55)c	116 (0 to 231)c
High (≥150)	Positive	High (≥300)	45 (26 to 59)c	128 (32 to 223)c
Low (< 150)	Positive	High (≥300)	40 (-3 to 65)	121 (-35 to 277)
High (≥150)	Positive	Low (< 300)	16 (-32 to 46)	-39 (-167 to 89)
Low (< 150)	Positive	Low (< 300)	36 (-5 to 60)	91 (-82 to 265)
High (≥150)	Negative	All patients	51 (17 to 71)c	198 (51 to 345)c
Low (< 150)	Negative	All patients	42 (23 to 56)c	135 (48 to 221)c
High (≥150)	Negative	High (≥300)	37 (-11 to 65)	177 (12 to 342)c
Low (< 150)	Negative	High (≥300)	50 (25 to 66)c	165 (43 to 286)c
High (≥150)	Negative	Low (< 300)	93 (35 to 99)c	221 (-115 to 558)
Low (< 150)	Negative	Low (< 300)	26 (-8 to 50)	110 (-4 to 224)
AER, annual exacerbation rate; CI, confidence interval; FEV1, forced expiratory volume in 1 second; IgE, immunoglobulin E; Q8W, every 8 weeks (every 4 weeks for the first three doses). aEstimates were calculated using a negative binomial model, with adjustment for study, treatment, region, oral corticosteroid use at time of randomization, and prior exacerbations. bEstimates 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. c p≤0.05 vs. placebo.

Conclusion:

Benralizumab reduced exacerbations and improved lung function for patients with severe uncontrolled asthma across categories of atopy status and baseline serum IgE concentrations, with more pronounced effects with blood eosinophils ≥300 cells/µL.