Jonathan Corren, MD, and Monica Kraft, MD, prepared useful practice aids pertaining to severe asthma for this CME activity titled "A MasterClass on New Avenues in Asthma Management: Finding the Right Patients for Targeted Therapies." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2yC6zBd. CME credit will be available until November 6, 2019.

1. DPP-4: dipeptidyl peptidase-4; FeNO: exhaled nitric oxide; IgE: immunoglobulin E; IL: interleukin; LTE4: leukotriene E4; Th2: T helper 2.
1. Chung KF et al. Eur Respir J. 2014;43:343-373. 2. Fajt ML, Wenzel SE. J Allergy Clin Immunol. 2015;135:299-310. 3. Willis JC, Lord GM. Nat Rev Immunol. 2015;15:323-329. 4. Wenzel SE. Nat Med. 2012;18:716-725. 5. Mohanan S et al. Exp Biol Med (Maywood). 2014;239:1531-1540.
6. Douwes J et al. Thorax. 2002;57:643-648. 7. Erzurum SC et al. Clin Chest Med. 2012;33:459‐471. 8. Shiobara S et al. Respir Res. 2016;17:28.
Access the activity, “A MasterClass on New Avenues in Asthma Management: Finding the Right Patients for Targeted Therapies,” at
www.peerview.com/DAB40.
Th2 Asthma Phenotype4,5
Non-Th2 Asthma Phenotype4-6
Smoking
associated
Obesity relatedEarly-onset allergic Late-onset eosinophilic Exercise induced Neutrophilic Smooth-muscle
mediated,
paucigranulocytic
Biomarkers May Identify Underlying Biologic Pathways of Asthma Phenotypes/Endotypes7,8
Asthma Patients1
One Size Fits All Stratified Medicine Personalized Medicine2,3
Most often associated with ...
 Type 1 hypersensitivity reactions
 Eosinophilic inflammation
 Response to corticosteroids
Often associated with ...
 Infections and environmental exposures (ozone, pollutants)
 Poor response to corticosteroids
Severe 5%-10%
UncontrolledSevere 2%
Asthma is now viewed as a
heterogeneous disease composed
of various phenotypes/endotypes2,4
Understanding major
phenotypes (Th2, non-Th2)
can help with diagnosis
and treatment selection
Biomarker Pathway
Blood/sputum eosinophils • Marker of excessive Th2 pathway activation (analyzing blood easier than sputum)
• Epithelial marker of type 2 airway inflammation (related to IL-13 release in the airway)
• Marker of excessive Th2 pathway activation
• Markers of IL-13 pathway/Th2 asthma
• Marker of cysteinyl leukotriene pathway activation
FeNO
Total and specific IgE
Periostin and DPP-4 (investigational)
LTE4
Insights Into the Heterogeneity of Severe Asthma
PRACTICE AID
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.

2. CS: corticosteroid; FEV1: forced expiratory volume in 1 second; IgE: immunoglobulin E; IL: interleukin; SBM: subepithelial basement membrane; Th2: T helper 2; Th17: T helper 17.
1. Wenzel SE. Nat Med. 2012;18:716-725. 2. Mohanan S et al. Exp Biol Med (Maywood). 2014;239:1531-1540. 3. Douwes J et al. Thorax. 2002;57:643-648.
Access the activity, “A MasterClass on New Avenues in Asthma Management: Finding the Right Patients for Targeted Therapies,” at
www.peerview.com/DAB40.
Early-onset
allergic
Late-onset
eosinophilic
Exercise induced Smoking
associated
Obesity related Smooth-muscle
mediated,
paucigranulocytic
Neutrophilic
Non-Th2 Asthma Phenotype1-3
Th2 Asthma Phenotype1,2
Genetics
17q12;
Th2-related genes
Response
to Therapy
CS-responsive;
Th2-targeted
Responsive to
anti–IL-5 therapy
and cysteinyl
leukotriene
modifiers;
CS-refractory
Responsive
to cysteinyl
leukotriene
modifiers,
β agonists, and
antibody to IL-9
Responsive to
weight loss,
antioxidants,
and possibly
hormonal therapy
Possibly
responsive to
macrolide
antibiotics
Pathobiology
and
Biomarkers
Specific IgE;
Th2 cytokines;
thick SBM
CS-refractory
eosinophilia; IL-5
Mast-cell activation;
Th2 cytokines;
cysteinyl
leukotrienes
Lack of Th2
biomarkers;
oxidative stress
No Th2
inflammation
Sputum
neutrophilia; Th17
pathways; IL-8
Clinical and
Physiological
Features
Allergic
symptoms and
other diseases
Possible asthma-
COPD overlap
syndrome
Sinusitis;
less allergic
Mild; intermittent
with exercise
Low FEV1
;
more air trapping
Primarily affects
women; very
symptomatic; airway
hyper-responsiveness
less clear
Natural
History
Early onset
(~3-10 y); mild
to severe
Adult onset;
often severe
Adult onset
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Features of Th2 and Non-Th2 Asthma Phenotypes
PRACTICE AID

3. CRTh2: chemoattractant receptor-homologous molecule expressed on T-helper 2 cells; IgE: immunoglobulin E; IL-#R: interleukin-# receptor; TSLP: thymic stromal lymphopoietin.
1. Xolair (omalizumab) Prescribing Information. https://www.gene.com/download/pdf/xolair_prescribing.pdf. Accessed September 21, 2018. 2. Nucala (mepolizumab) Prescribing Information.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125526Orig1s000Lbl.pdf. Accessed September 21, 2018. 3. Cinqair (reslizumab) Prescribing Information. http://cinqair.com/pdf/
PrescribingInformation.pdf. Accessed September 21, 2018. 4. Fasenra (benralizumab) Prescribing Information. https://www.azpicentral.com/fasenra/fasenra_pi.pdf#page=1. Accessed September 21, 2018.
5. Dupixent (dupilumab) Prescribing Information. https://www.regeneron.com/sites/default/files/Dupixent_FPI.pdf. Accessed October 22, 2018. 6. https://www.prnewswire.com/news-releases/
tezepelumab-granted-breakthrough-therapy-designation-by-us-fda-for-the-treatment-of-patients-with-severe-asthma-without-an-eosinophilic-phenotype-300708680.html. Accessed September 21, 2018.
7. https://clinicaltrials.gov/ct2/show/NCT03347279. Accessed September 21, 2018. 8. https://clinicaltrials.gov/ct2/show/NCT03406078. Accessed September 21, 2018. 9. Corren J et al. N Engl J Med.
2017;377:936-946. 10. https://clinicaltrials.gov/ct2/show/NCT02563067. Accessed September 21, 2018. 11. https://clinicaltrials.gov/ct2/show/NCT03052517. Accessed September 21, 2018.
12. https://clinicaltrials.gov/ct2/show/NCT02555683. Accessed September 21, 2018.
Access the activity, “A MasterClass on New Avenues in Asthma Management: Finding the Right Patients for
Targeted Therapies,” at www.peerview.com/DAB40.
Agent/Target Indication/Current Status Route/Dosing
Patients ≥6 y with moderate to
severe persistent allergic asthma
inadequately controlled with
inhaled corticosteroids
Subcutaneous
75 mg to 375 mg every 2-4 weeks
(dosage based on IgE level
and body weight)
Add-on maintenance treatment of
patients ≥12 y with severe asthma
and an eosinophilic phenotype
Subcutaneous
100 mg every 4 weeks
Add-on maintenance treatment of
patients ≥18 y with severe asthma
and an eosinophilic phenotype
Intravenous infusion
3 mg/kg every 4 weeks over
20-50 minutes
Add-on maintenance treatment of
patients ≥12 y with severe asthma
and an eosinophilic phenotype
Subcutaneous
30 mg every 4 weeks for first
3 doses, then every 8 weeks
Add-on maintenance treatment of
patients ≥12 years with moderate to
severe asthma with an eosinophilic
phenotype or with oral
corticosteroid-dependent asthma
Subcutaneous
Initial dose of 400 mg followed by 200 mg
every 2 weeks or initial dose of 600 mg
followed by 300 mg every 2 weeks
Phase 3 trials; breakthrough
designation for
noneosinophilic phenotype
Subcutaneous
70 mg and 210 mg every 4 weeks and
280 mg every 2 weeks tested in
phase 2 trials
Phase 3 trials Oral
Dupilumab5
IL-4Rα
(IL-4/IL-13)
Tezepelumab6-9
TSLP
Fevipiprant10-12
CRTh2
Investigational
Omalizumab1
IgE
Mepolizumab2
IL-5
Reslizumab3
IL-5
Benralizumab4
IL-5Rα/βc
Approved
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
A Guide to Biologic Therapies for Severe,
Uncontrolled Asthma
PRACTICE AID