Pneumologie 2018; 72(S 01): S14
DOI: 10.1055/s-0037-1619154
Sektion 7 – Klinische Pneumologie
Posterbegehung – Titel: Asthma I
Georg Thieme Verlag KG Stuttgart · New York

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

Authors

  • BE Chipps

    1   Capital Allergy and Respiratory Disease Center, Sacramento, CA, USA

  • P Newbold

    2   Medimmune LLC, Gaithersburg, MD, USA

  • I Hirsch

    3   Astrazeneca, Gaithersburg, MD, USA

  • F Trudo

    3   Astrazeneca, Gaithersburg, MD, USA

  • M Goldman

    3   Astrazeneca, Gaithersburg, MD, USA
Further Information

Publication History

Publication Date:
21 February 2018 (online)

Also available at
 

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.