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Changing Paradigms in the Treatment of Severe Asthma: The Role of Biologic Therapies

https://doi.org/10.1016/j.jaip.2016.11.029Get rights and content

Cytokine antagonists are monoclonal antibodies that offer new treatment options for refractory asthma but will also increase complexity because they are effective only for patients with certain asthma subtypes that remain to be more clearly defined. The clinical and inflammatory heterogeneity within refractory asthma makes it difficult to manage the disease and to determine which, if any, biologic therapy is suitable for a specific patient. The purpose of this article is to provide a data-driven discussion to clarify the use of biologic therapies in patients with refractory asthma. We first discuss the epidemiology and pathophysiology of refractory asthma. We then interpret current evidence for biomarkers of eosinophilic or type 2-high asthma so that clinicians can determine potential treatments for patients based on knowledge of their effectiveness in specific asthma phenotypes. We then assess clinical data on the efficacy, safety, and mechanisms of action of approved and pipeline biologic therapies. We conclude by discussing the potential of phenotyping or endotyping refractory asthma and how biologic therapies can play a role in treating patients with refractory asthma.

Key words

Severe asthma
Refractory asthma
Biologic therapy
Monoclonal antibody
Eosinophil
FeNO
Periostin

Abbreviations used

AE
Adverse event
ATS
American Thoracic Society
CI
Confidence interval
CPK
Creatinine phosphokinase
DPP-4
Dipeptidyl peptidase-4
ED
Emergency department
EPR-3
Expert Panel Report 3
ERS
European Respiratory Society
FeNO
Fractional exhaled nitric oxide
FEV1
Forced expiratory volume in 1 second
GINA
Global Initiative for Asthma
IgE
Immunoglobulin E
ICS
Inhaled corticosteroids
ILC2
Group 2 innate lymphoid
IL-4Rα
IL-4 receptor alpha
LABA
Long-acting β-agonist
NAEPP
National Asthma Education and Prevention Program (US)
OCS
Oral corticosteroids
RR
Relative risk
SAE
Serious adverse event
SC
Subcutaneous
TENOR
The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens
Th2
T helper cell type 2
U-BIOPRED
Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes

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The authors were part of an expert panel hosted by the Cohen Family Asthma Institute at National Jewish Health in Denver, Colorado. This activity is supported by an independent educational grant from Teva Pharmaceuticals.

Conflicts of interest: R. K. Katial has received consultancy fees and travel support from Teva Pharmaceuticals; has received consultancy fees from AstraZeneca and Meda; and has received lecture fees from Meda. G. W. Bensch has received consultancy and lecture fees and travel support from Teva Pharmaceuticals; and payment for lectures including service on speakers bureaus from AstraZeneca. W. W. Busse has received consultancy fees and travel support from Teva Pharmaceuticals; is on the Boston Scientific and Circassia Data Safety Monitoring Boards; is on the ICON Clinical Research Limited Study Oversight Committee; has received consultancy fees from Novartis, GlaxoSmithKline, Genentech, Roche, Pfizer, Merck, Boehringer Ingelheim, Sanofi, AstraZeneca, Takeda, Aerocrine, 3M, and PrEPBiopharm; has received research support from National Institutes of Health (NIH)-National Institute of Allergy and Infectious Diseases (NIAID) and NIH-National Heart, Lung, and Blood Institute; and receives royalties from Elsevier. B. E. Chipps has received consultancy fees and travel support from Teva Pharmaceuticals; has received consultancy and lecture fees from AstraZeneca, Boehringer Ingelheim, Genentech, Meda, Merck, and Novartis. J. L. Denson declares no relevant conflicts of interest. A. N. Gerber has received consultancy fees from Teva Pharmaceuticals and Revon Systems, the latter outside the current work. J. S. Jacobs has received travel support from Teva Pharmaceuticals; has received consultancy fees from Teva Pharmaceuticals and Sanofi-Aventis; has received lecture fees from Teva Pharmaceuticals; and has received research support from Teva Pharmaceuticals, Genentech, and AstraZeneca. M. Kraft has received consultancy fees from Teva Pharmaceuticals and AstraZeneca; has received research support from the NIH, Chiesi, Roche, and Sanofi; and receives royalties from Elsevier. R. J. Martin has received consultancy fees from Teva Pharmaceuticals and PMD Healthcare; has received research support from MedImmune, NHLBI, and Chiesi Farmaceutici SpA; has received travel support from the Respiratory Effectiveness Group; and is on the advisory boards for AstraZeneca and Genentech. P. Nair has received travel support from Teva Pharmaceuticals; is on the scientific advisory boards for Teva Pharmaceuticals, AstraZeneca, and Sanofi; has received consultancy fees from Teva Pharmaceuticals, Sanofi, Roche, Daiichi Sankyo, Novartis, and Knopp; has received research support from AstraZeneca, Novartis, Sanofi, Boehringer Ingelheim, Roche, Teva Pharmaceuticals, and GlaxoSmithKline; and has received lecture fees from AstraZeneca, Novartis, and Teva Pharmaceuticals. M. E. Wechsler has received consultancy fees from Sepracor/Sunovion, Asthmatx/Boston Scientific, Merck, Regeneron, MedImmune, Ambitbio, Vectura, Sanofi, Teva Pharmaceuticals, Mylan, AstraZeneca, Genentech, Meda, Theravance, Novartis, Boehringer Ingelheim, GlaxoSmithKline, Tunitas, and Gliacure; and is on the advisory board for Teva Pharmaceuticals.

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