TY - JOUR
T1 - Targeting downstream type 2 cytokines or upstream epithelial alarmins for severe asthma
AU - Chan, Rory
AU - Stewart, Kirsten
AU - Misirovs, Rashad
AU - Lipworth, Brian
N1 - Funding Information:
Conflicts of Interest: B. J. Lipworth reports nonfinancial support (equipment) from GSK; grants, personal fees (consulting, talks, and advisory board), and other support (attending ATS and ERS) from AstraZeneca; grants, personal fees (consulting, talks, and advisory board), and other support (attending ERS) from Teva; personal fees (consulting) from Sanofi; personal fees (consulting, talks, and advisory board) from Circassia in relation to the submitted work; personal fees (consulting) from Lupin, Glenmark, Vectura, Dr Reddy, and Sandoz; grants, personal fees (consulting, talks, and advisory board), and other support (attending BTS) from Boehringer Ingelheim; and grants and personal fees (advisory board and talks) from Mylan outside of the submitted work. The son of B. J. Lipworth is presently an employee of AstraZeneca. The rest of the authors declare that they have no relevant conflicts of interest. No funding was received for this work.
Publisher Copyright:
© 2022 American Academy of Allergy, Asthma & Immunology
PY - 2022/6/1
Y1 - 2022/6/1
N2 - Biologics, including omalizumab, mepolizumab, benralizumab, and dupilumab, targeting downstream IgE, cytokines IL-5, and IL-4/13, respectively, have shown promising effects in terms of reduction in annualized asthma exacerbation rates (AER), oral corticosteroid-sparing effects, improvements in forced expiratory volume in 1 second, and improved Asthma Control Questionnaire scores. However, despite these welcome advances, approximately 30% of patients with severe asthma receiving biologics tailored to their specific downstream type 2 biomarkers, including total IgE, peripheral blood eosinophils, and fractional exhaled nitric oxide, do not experience meaningful improvements in their AER. Instead of blocking downstream cytokines, targeting upstream epithelial alarmins, including IL-33, thymic stromal lymphopoietin, and IL-25, has been proposed to tackle the immunologic heterogeneity of asthma. This review article aims to pragmatically summarize the latest key clinical data on antialarmin therapies in severe asthma and put these findings into context with regard to currently available downstream cytokine blockers.
AB - Biologics, including omalizumab, mepolizumab, benralizumab, and dupilumab, targeting downstream IgE, cytokines IL-5, and IL-4/13, respectively, have shown promising effects in terms of reduction in annualized asthma exacerbation rates (AER), oral corticosteroid-sparing effects, improvements in forced expiratory volume in 1 second, and improved Asthma Control Questionnaire scores. However, despite these welcome advances, approximately 30% of patients with severe asthma receiving biologics tailored to their specific downstream type 2 biomarkers, including total IgE, peripheral blood eosinophils, and fractional exhaled nitric oxide, do not experience meaningful improvements in their AER. Instead of blocking downstream cytokines, targeting upstream epithelial alarmins, including IL-33, thymic stromal lymphopoietin, and IL-25, has been proposed to tackle the immunologic heterogeneity of asthma. This review article aims to pragmatically summarize the latest key clinical data on antialarmin therapies in severe asthma and put these findings into context with regard to currently available downstream cytokine blockers.
KW - Antialarmins
KW - Biologics
KW - Brodalumab
KW - Cytokines
KW - Itepekimab
KW - Severe asthma
KW - Tezepelumab
UR - http://www.scopus.com/inward/record.url?scp=85125126133&partnerID=8YFLogxK
U2 - 10.1016/j.jaip.2022.01.040
DO - 10.1016/j.jaip.2022.01.040
M3 - Article
C2 - 35131510
SN - 2213-2198
VL - 10
SP - 1497
EP - 1505
JO - The Journal of Allergy and Clinical Immunology: In Practice
JF - The Journal of Allergy and Clinical Immunology: In Practice
IS - 6
ER -