Jonathan Corren, MD, discusses asthma management in this CME activity titled "Targeted Treatment in Severe Asthma: Moving Toward Precision Medicine." For the full presentation, downloadable infographics, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2It37Pk. CME credit will be available until June 3, 2019.

1. This additional resource has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Insights Into the Heterogeneity
of Severe Asthma
DPP-4: dipeptidyl peptidase-4; FeNO: exhaled nitric oxide; IgE: immunoglobulin E; IL-13: interleukin 13; LTE4
: leukotriene E4; Th2: T helper 2.
1. Erzurum SC et al. Clin Chest Med. 2012;33:459-471. 2. Shiobara S et al. Respir Res. 2016;17:28.
ADDITIONAL RESOURCES
Access the activity,“Targeted Treatment in Severe Asthma: Moving Toward Precision Medicine,”
at www.peerview.com/CFA930.
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 (investigational)
• Marker of cysteinyl leukotriene pathway activation
FeNO
Total and specific IgE
Periostin and DPP-4
LTE4
Biomarker
Biomarkers That May Help Identify the Underlying Biologic Pathways
of Asthma Phenotypes/Endotypes1,2
Pathway

2. Access the activity,“Targeted Treatment in Severe Asthma: Moving Toward
Precision Medicine,”at www.peerview.com/CFA930.
New Horizons in the Treatment
of Severe Asthma
This additional resource has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
ADDITIONAL RESOURCES
• Similar results observed for the 200-mg Q2W dose group
• Extent of patient response correlated with blood eosinophils and other markers—less activity was observed
in patients with <150 eosinophils/mcL
QUEST Study: Improvements With Dupilumab 300 mg Q2W
Clinical Trial Data for Emerging Treatment Options: Dupilumab5-9
a
P < .001 vs placebo for all groups.
Overall rates of AEs, deaths, infections, conjunctivitis, herpes,
and discontinuations comparable with placebo
Injection-Site Reactions
Dupilumab 300 mg Q2W: 18.4%
Matched placebo: 10.3%
Overall Population
≥300 Eosinophils/mcL
1,795 Adults
107 Adolescents
9
18
0
5
10
15
20
25
30
FEV1
at 12 Wk, %a
130 mL
240 mL
Exacerbations at 52 Wk, %a
-46
-67
-60
-80
-40
-20
0
Parameter Mepolizumab Reslizumab Benralizumab
Patient age ≥12 y ≥18 y ≥12 y
Route SubQ IV SubQ
Dosing Q4W
Q4W
Adjusted
by weight
Q4W for
first 3 doses,
then Q8W
Eosinophils ≥150/mcL ≥400/mcL ≥150/mcL
Which Anti–IL-5 to Choose?1-4
No head-to-head studies
• Rates of AEs, including infections, conjunctivitis, and herpes, comparable between groups
• Injection-site reactions more common in dupilumab group (9%) vs placebo group (4%)
• Increase in eosinophil counts more frequent in dupilumab group (14%) vs placebo group (1%);
mostly mild and resolved spontaneously
Improvements in lung function and exacerbations
observed despite decreased OCS use
Outcomes
Overall Population
Patients With
≥300 Eosinophils/mcL
Dupilumab
300 mg Q2W
P vs Placebo
Dupilumab
300 mg Q2W
P vs Placebo
$ Maintenance OCS use 70% < .0001 80% .0001 (nominal)
$ Exacerbations 59% < .0001 71% Not listed
# FEV1
15% (220 mL) .0007 25% (320 mL) .0049 (nominal)
LIBERTY ASTHMA VENTURE, 24-Wk Phase 3 Data, 210 Patients Requiring Oral Steroids

3. Access the activity,“Targeted Treatment in Severe Asthma: Moving Toward
Precision Medicine,”at www.peerview.com/CFA930.
New Horizons in the Treatment
of Severe Asthma
This additional resource has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
ADDITIONAL RESOURCES
• Significantly improved annualized rate of asthma exacerbations at wk 52 in all dose groups
• Significantly improved prebronchodilator FEV1
at wk 52 in all dose groups
• Greater proportion of patients in tezepelumab groups either well or partially controlled at wk 52
• 2 patients in medium-dose group, 3 in high-dose group, and 1 in placebo group discontinued because of AEs
Subpopulation Analysis
Blood Eosinophil Count,
cells/mcL
Clinical Trial Data for Emerging Treatment Options: Tezepelumab10-13
0
0.2
0.4
0.6
0.8
1.0
FeNO,
ppb
Th2
Status
HighLow≥24<24≥250<250
AnnualizedRateofExacerbations,
Events/Patient-Year
P = .03 P = .001
P = .001
P = .02
P = .006
P = .006
P = .03
P < .001
P < .001
P < .001
P = .008
P < .001
P = .004
P = .005
P = .02
n Placebo
n Low-dose tezepelumab
(70 mg Q4W)
n Medium-dose tezepelumab
(210 mg Q4W)
n High-dose tezepelumab
(280 mg Q2W)
Significantly $ eosinophilic
inflammation in sputum and
bronchial submucosa
in patients with persistent
moderate to severe asthma
and sputum eosinophilia
Significantly improved AQLQ(S) scores, post-bronchodilator FEV1
, and functional residual capacity in all patients,
and ACQ-7 scores in the predefined subgroup of patients who had uncontrolled asthma at baseline
Favorable safety profile, with no deaths or serious AEs reported
Clinical Trial Data for Emerging Treatment Options: Fevipiprant14-19
16
8
4
2
1
0.5
1260 18
Treatment Washout
Time, wk
FoldReductioninSputum
EosinophilCount
Fevipiprant
Placebo
P = .0014
P = .0077
P = .92

4. Access the activity,“Targeted Treatment in Severe Asthma: Moving Toward
Precision Medicine,”at www.peerview.com/CFA930.
New Horizons in the Treatment
of Severe Asthma
This additional resource has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
ACQ-7: Asthma Control Questionnaire–7; AEs: adverse events; AQLQ(S): standardized Asthma Quality of Life Questionnaire; BID: twice daily; FeNO: exhaled nitric oxide; FEV1
: forced expiratory
volume in 1 second; IL-5: interleukin 5; OCS: oral corticosteroids; QD: once daily; QxW: every x weeks; Th2: T helper 2.
1. Maselli D et al. J Asthma Allergy. 2016;9:155-162. 2. Nucala (mepolizumab) Prescribing Information. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125526Orig1s000Lbl.pdf.
Accessed March 5, 2018. 3. Cinqair (reslizumab) Prescribing Information. http://cinqair.com/pdf/PrescribingInformation.pdf. Accessed May 4, 2018. 4. Fasenra (benralizumab) Prescribing
Information. https://www.azpicentral.com/fasenra/fasenra_pi.pdf. Accessed March 5, 2018. 5. https://www.prnewswire.com/news-releases/fda-to-review-dupixent-dupilumab-as-potential-
treatment-for-moderate-to-severe-asthma-300607094.html. Accessed May 4, 2018. 6. https://www.prnewswire.com/news-releases/regeneron-and-sanofi-announce-positive-dupilumab-
topline-results-from-phase-3-trial-in-uncontrolled-persistent-asthma-300516839.html. Accessed May 4, 2018. 7. https://globenewswire.com/news-release/2017/10/31/1169458/0/en/
Sanofi-Dupilumab-Significantly-Reduced-Steroid-Use-Asthma-Attacks-and-Improved-Lung-Function-in-a-Phase-3-Study-of-People-with-Severe-Steroid-Dependent-Asthma.html. Accessed
May 4, 2018. 8. Castro M et al. N Engl J Med. May 21, 2018. [Epub ahead of print]. 9. Rabe KF et al. N Engl J Med. May 21, 2018. [Epub ahead of print]. 10. https://www.clinicaltrials.gov/ct2/show/
NCT03347279. Accessed May 4, 2018. 11. Corren J et al. N Engl J Med. 2017;377:936-946. 12. Corren J et al. American Academy of Allergy, Asthma and Immunology and World Allergy Organization
2018 Joint Congress (AAAAI/WAO 2018). Abstract 257. 13. Corren J et al. American Thoracic Society Conference 2018 (ATS 2018). Abstract A5962. 14. https://www.clinicaltrials.gov/ct2/show/
NCT03052517. Accessed May 4, 2018. 15. https://www.clinicaltrials.gov/ct2/show/NCT02563067. Accessed May 4, 2018. 16. https://www.clinicaltrials.gov/ct2/show/NCT02555683. Accessed May 4,
2018. 17. Bateman ED et al. Eur Respir J. 2017;50:1700670. 18. Kerwin EM et al. ATS 2018. Abstract 1408. 19. Gonem S et al. Lancet Respir Med. 2016;4:699-707.
ADDITIONAL RESOURCES
a
P values are not adjusted for multiplicity.
Change in FEV1
After 12 Wk of Treatment
Treatment Group Difference vs Placebo, L (95% CI) Pa
Fevipiprant 1 mg QD 0.075 (-0.048 to 0.198) .2296
Fevipiprant 3 mg QD 0.087 (-0.035 to 0.209) .1609
Fevipiprant 10 mg QD 0.002 (-0.125 to 0.129) .9760
Fevipiprant 30 mg QD 0.091 (-0.027 to 0.210) .1311
Fevipiprant 50 mg QD 0.052 (-0.071 to 0.175) .4072
Fevipiprant 75 mg QD 0.111 (-0.007 to 0.230) .0652
Fevipiprant 150 mg QD 0.164 (0.044 to 0.285) .0075
Fevipiprant 300 mg QD 0.120 (0.003 to 0.237) .0442
Fevipiprant 450 mg QD 0.077 (-0.012 to 0.167) .0901
Fevipiprant 2 mg BID -0.014 (-0.135 to 0.107) .8230
Fevipiprant 25 mg BID 0.145 (0.030 to 0.260) .0133
Fevipiprant 75 mg BID 0.179 (0.052 to 0.307) .0059
Fevipiprant 150 mg BID 0.064 (-0.054 to 0.181) .2871
Montelukast 10 mg 0.134 (0.045 to 0.222) .0033
Significant improvement in
primary endpoint of change in
predose FEV1
at wk 12
(P = .0035) with a maximum
model-averaged difference to
placebo of 0.112 L
Fevipiprant Phase 2 Data in
Uncontrolled Allergic Asthma