PMID- 29409951
OWN - NLM
STAT- MEDLINE
DCOM- 20190306
LR  - 20190306
IS  - 1534-4436 (Electronic)
IS  - 1081-1206 (Linking)
VI  - 120
IP  - 5
DP  - 2018 May
TI  - Benralizumab efficacy by atopy status and serum immunoglobulin E for patients 
      with severe, uncontrolled asthma.
PG  - 504-511.e4
LID - S1081-1206(18)30061-9 [pii]
LID - 10.1016/j.anai.2018.01.030 [doi]
AB  - BACKGROUND: Patients with severe asthma can have eosinophilic inflammation and/or 
      allergen sensitization. Benralizumab is an anti-eosinophilic monoclonal antibody 
      indicated for add-on maintenance treatment of patients with severe asthma aged 12 
      years and older, and with an eosinophilic phenotype. OBJECTIVE: To investigate 
      the efficacy of benralizumab by atopic status and serum immunoglobulin E (IgE) 
      concentrations. METHODS: We analyzed pooled results from the SIROCCO 
      (NCT01928771) and CALIMA (NCT01914757) phase III studies. Patients 12 to 75 years 
      old with severe, uncontrolled asthma on high-dosage inhaled corticosteroids plus 
      long-acting beta(2)-agonists received 30 mg of subcutaneous benralizumab every 4 
      weeks or every 8 weeks (first 3 doses every 4 weeks) or placebo every 4 weeks. 
      The analysis stratified patients who did and did not meet similar 
      omalizumab-qualifying criteria of atopy and serum IgE levels 30 to 700 kU/L. 
      Patients also categorized as having high serum IgE (>/=150 kU/L) or low serum IgE 
      (<150 kU/L) and as having atopy or no atopy. Efficacy outcomes were for all 
      patients and by blood eosinophil counts and included annual exacerbation rate 
      ratio and pre-bronchodilator forced expiratory volume in 1 second change at 
      treatment end vs placebo. RESULTS: Benralizumab every 8 weeks decreased 
      exacerbations by 46% (95% confidence interval 26-61, P = .0002) and increased 
      forced expiratory volume in 1 second by 0.125 L (95% confidence interval 
      0.018-0.232, P = .0218) vs placebo for patients with at least 300 eosinophils/muL 
      who met the atopy and IgE criteria. For patients with eosinophilia and high or 
      low IgE, treatment with benralizumab every 8 weeks resulted in 42% and 43% 
      decreases in exacerbation rate (P </= .0004) and 0.123- and 0.138-L increases in 
      forced expiratory volume in 1 second (P </= .0041) vs placebo, respectively. 
      CONCLUSION: Benralizumab treatment decreased exacerbations and improved lung 
      function for patients with severe, uncontrolled eosinophilic asthma regardless of 
      serum IgE concentrations and atopy status.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Chipps, Bradley E
AU  - Chipps BE
AD  - Capital Allergy and Respiratory Disease Center, Sacramento, California. 
      Electronic address: chipps@capitalallergy.com.
FAU - Newbold, Paul
AU  - Newbold P
AD  - MedImmune LLC, Gaithersburg, Maryland.
FAU - Hirsch, Ian
AU  - Hirsch I
AD  - AstraZeneca, Gaithersburg, Maryland.
FAU - Trudo, Frank
AU  - Trudo F
AD  - AstraZeneca, Wilmington, Delaware.
FAU - Goldman, Mitchell
AU  - Goldman M
AD  - AstraZeneca, Gaithersburg, Maryland.
LA  - eng
SI  - ClinicalTrials.gov/NCT01928771
SI  - ClinicalTrials.gov/NCT01914757
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180201
PL  - United States
TA  - Ann Allergy Asthma Immunol
JT  - Annals of allergy, asthma & immunology : official publication of the American 
      College of Allergy, Asthma, & Immunology
JID - 9503580
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Adrenergic beta-2 Receptor Agonists)
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 71492GE1FX (benralizumab)
SB  - IM
MH  - Adolescent
MH  - Adrenal Cortex Hormones/*therapeutic use
MH  - Adrenergic beta-2 Receptor Agonists/*therapeutic use
MH  - Adult
MH  - Aged
MH  - Anti-Asthmatic Agents/*therapeutic use
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Asthma/blood/*drug therapy/immunology/physiopathology
MH  - Child
MH  - Disease Progression
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Therapy, Combination
MH  - Eosinophils/drug effects/immunology/pathology
MH  - Female
MH  - Forced Expiratory Volume/drug effects/physiology
MH  - Humans
MH  - Immunoglobulin E/*blood
MH  - Male
MH  - Middle Aged
MH  - Pulmonary Eosinophilia/blood/*drug therapy/immunology/physiopathology
MH  - Severity of Illness Index
MH  - Treatment Outcome
EDAT- 2018/02/08 06:00
MHDA- 2019/03/07 06:00
CRDT- 2018/02/08 06:00
PHST- 2017/11/06 00:00 [received]
PHST- 2018/01/09 00:00 [revised]
PHST- 2018/01/24 00:00 [accepted]
PHST- 2018/02/08 06:00 [pubmed]
PHST- 2019/03/07 06:00 [medline]
PHST- 2018/02/08 06:00 [entrez]
AID - S1081-1206(18)30061-9 [pii]
AID - 10.1016/j.anai.2018.01.030 [doi]
PST - ppublish
SO  - Ann Allergy Asthma Immunol. 2018 May;120(5):504-511.e4. doi: 
      10.1016/j.anai.2018.01.030. Epub 2018 Feb 1.