Asthma Part 4 - Advanced Therapies in Severe Asthma_Khurana.pptx
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This document discusses advanced therapies for severe asthma, including biologics. It defines severe asthma and notes that approximately 5-10% of adults have severe asthma. It reviews the available biologic therapies for type 2 asthma, including their mechanisms of action and administration routes. These include anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4Ra (dupilumab) therapies. It discusses treatment options for type 2 low asthma, including macrolide antibiotics, bronchial thermoplasty, and anti-TSLP antibody tezepelumab.
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Asthma Part 4 - Advanced Therapies in Severe Asthma_Khurana.pptx
- 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 45 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: 343373
- 6. 息 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!