Asthma

1. Asthma- Part 4
Advanced Therapies in Severe Asthma
Sandhya Khurana, MD, FCCP
Professor, Pulmonary & Critical Care Medicine
Director, Mary Parkes Center for Asthma, Allergy & Pulmonary Care
University of Rochester, NY

2. • Define severe asthma and prevalence
• Review available biologic therapies and mechanism of action
• Discuss management of non-T2 asthma
Learning Objectives

3.  Research funding – GSK, Sanofi
 Royalties – Springer
Disclosures

4. Asthma that requires treatment at GINA steps 4–5 or systemic CS for
>50% of the previous year to prevent it from becoming ‘‘uncontrolled’’
or remains ‘‘uncontrolled‘‘ despite this therapy
Or
Controlled asthma that worsens on tapering of these high doses of ICS
or systemic CS (or additional biologics)
Severe Asthma - Definition
Chung et al. Eur Respir J 2014; 43: 343–373

6. © Global Initiative for Asthma, www.ginasthma.org
What proportion of asthma in adults is severe?
GINA 2021, Box 3-15: What proportion of adults with asthma have severe asthma?

7. Available Biologics in Asthma
Drug Mechanism Route Setting
Omalizumab Anti-IgE Subcutaneous Home/Clinic
Mepolizumab Anti-IL5 Subcutaneous Home/Clinic
Reslizumab Anti-IL5 Intravenous Clinic
Benralizumab Anti-IL5Ra Subcutaneous Home/Clinic
Dupilumab Anti-IL4Ra Subcutaneous Home
Omalizumab
Dupilumab
Mepolizumab
Reslizumab
Benralizumab

8.  Anti-IgE humanized recombinant monoclonal antibody
 Binds to free circulating IgE at the same site as high-affinity IgE receptor
 Indication
– Moderate-Severe allergic asthma
– Serum IgE 30-700 IU/ml with sensitivity to >1 perennial allergen
 AEs: Small risk of delayed anaphylactic reactions (0.2%)
 Administration: Subcutaneous injection every 2-4 weeks
Anti-IgE Monoclonal Antibody (Omalizumab)

9.  Anti-IL5 monoclonal antibodies (mepolizumab, reslizumab)
 Anti-IL5 receptor monoclonal antibody (benralizumab)
 Indication: Add-on maintenance therapy for patients with
severe asthma with an eosinophilic phenotype
 Administration:
– Mepolizumab: 100 mg subcutaneous injection every 4 weeks
– Reslizumab: Weight-based intravenous infusion every 4 weeks
– Benralizumab: 30 mg subcutaneous every 4 weeks x 3, then every 8 weeks
Anti-IL5 Therapy
IL-5
IL-5R

10.  Fully human monoclonal antibody
 Binds to alpha subunit of IL-4 receptor
 Inhibits the activity of both Il-4 and IL-13
 Indication: moderate-to-severe, eosinophilic asthma and OCS-dependent asthma
 Dose: 400 mg or 600 mg initial loading dose, then 200mg or 300 mg every 2 weeks
subcutaneously
 Higher dose in OCS-dependent asthma or comorbid atopic dermatitis
Anti-IL4R antibody (dupilumab)

11. Biologics for Type 2 Asthma
ICER 2018
6

12. Biologics for Type 2 Asthma: Efficacy
Drug
Asthma
Exacerbations
Rate Ratio
OCS
% dose
reduction
% Off OCS FEV1 (L) ACQ
Omalizumab 0.52 - - 0.06 -
(0.37-0.73) (0.02-0.10)
Mepolizumab 0.45 -50% vs 0% 14% vs 8% 0.10 -0.42
(0.36-0.55) (0.01-0.18) (-0.56 to -0.28)
Reslizumab 0.43 - - 0.12 -0.27
(0.33-0.55) (0.08-0.16) (-0.36 to -0.19)
Benralizumab 0.59 -75% vs -25% 52% vs 19%
0.13 -0.23
(0.51-0.68) (0.08-0.19) (-0.34 to -0.12)
Dupilumab
200mg
0.52
(0.41-0.66)
- - 0.14
(0.08-0.19)
-0.39
(-0.53 to -0.25)
Dupilumab
300mg
0.54
(0.43-0.68)
-70% vs -42% 52% vs 29%
0.13
(0.08-0.18)
-0.22
(-0.36 to -0.08)

13. Treatment of Type 2 Low Asthma
 40 - 50% of asthma patients do not have Type 2 inflammation
 Severe, uncontrolled asthma without evidence for Type 2 inflammation
referred to as ‘Type 2 low asthma’
 Potential targets for Type 2 low asthma:
 Macrolide antibiotics
 Bronchial Thermoplasty

14. N=420
Symptomatic asthma despite ICS/LABA
Azithromycin 500 mg thrice weekly vs
placebo for 48 weeks
Azithromycin in asthma
AMAZES
Gibson, Peter G et al. The Lancet 2017

15. Bronchial Thermoplasty
AIR2 Trial
Improvement in Asthma Quality of Life
Reduction in Health Care Utilization
Castro M, et al, Am J Respir Crit Care Med 2010; 81 : 116

16. Tezepelumab – anti-TSLP ab
Menzies-Gow et al. Respir Res 2020
Menzies-Gow et al. NEJM 2021

17. Thank you!