Biologic Therapy for Patients with Severe Asthma

Introduction

Presenter: Dr. Jonathan Koren, Associate Clinical Professor of Medicine and Pediatrics, UCLA.
Co-presenters: Dr. Michael Wexler and Sanaz Eftikari.
Event: Global Education Group in collaboration with the Asthma and Allergy Foundation of America at Immunology Live.
Interactive Session: Encouraging real-time questions from the audience.

Identify how epithelial alarmans impact type 2 and non-type 2 downstream inflammation in asthma.
Differentiate the mechanisms of action of available biologics for severe asthma.
Summarize efficacy and safety data related to alarmant blockade with biologic therapy targeting TSLP (thymic stromal lymphopoietin).
Identify patients who may benefit from TSLP-targeted treatment.

Severe Asthma: Requires GINA level 4 or 5 medications to be controlled or remains uncontrolled despite treatment.
Uncontrolled Severe Asthma: Defined by:
- Exacerbations requiring oral steroids.
- Serious exacerbations requiring escalation of care.
- Persistent airflow limitation (FEV1 < 80% of predicted).

Majority of patients report dissatisfaction with asthma control.
- Recent patient program showed about 50% reported their asthma control needed improvement.

Pathways: Asthma is categorized into three main pathobiologic pathways:
1. Type 2 (Th2) Asthma: Involves allergic responses, IgE, IL-4, and IL-13.
2. Eosinophilic Non-allergic Asthma: High eosinophils, related to IL-5.
3. Low Type 2 Asthma: Heterogeneous, may include Th17 and neutrophils.
Phenotypes vs. Endotypes:
- Phenotype: Observable characteristics influenced by genetics and environment.
- Endotype: Biological mechanisms underlying phenotypes (cytokines, cells involved).

Type 2 Asthma: Includes allergic asthma, eosinophilic asthma, and aspirin-exacerbated respiratory disease.
Type 2 Low Asthma: Often late-onset; patients may present with obesity, GERD, and chronic rhinosinusitis.

Epithelial alarmants (TSLP, IL-25, IL-33) play key roles in asthma pathophysiology:
- Induction of inflammation.
- Structural airway changes.
- Interaction with smooth muscle leading to airway hyper-responsiveness.

Biologics: Target specific pathways in asthma management for severe asthma patients (5-10% of population).
Biologic Therapies:
- Dupilumab: Blocks IL-4, IL-13 receptors, reducing exacerbations and improving lung function.
- Omalizumab: Anti-IgE therapy; reduces exacerbations and oral steroid use.
- Mepolizumab, Reslizumab, Benrolizumab: Anti-IL-5 therapies leading to reduced eosinophils and exacerbations.
- Tesipelumab: New anti-TSLP monoclonal antibody shown to reduce exacerbations in low type 2 asthma as well.

Biologics show:
- Reduction in asthma exacerbations (25-75% depending on the drug).
- Improved quality of life.
- Potential for corticosteroid sparing effects.
Safety: Generally well tolerated; adverse events similar to placebo.

Tezipleumab: Approved for patients 12 years and up with severe asthma.
- Significant reductions in exacerbations (61-71% across doses).
- Effective regardless of eosinophil counts or airway hyper-responsiveness status.

Importance of assessing patient-specific factors (comorbidities, biomarker levels) in treatment decisions.
Discussion of when to switch or discontinue biologic therapies.

Ongoing need for targeted therapies in non-type 2 asthma.
Importance of awareness and education on biologics for patients with severe asthma.
Continued research and exploration of diverse patient demographics in future studies.

Encouraged audience participation and addressed questions throughout the presentation.
Thanked audience and sponsors for their attention and participation.