Treating Severe Asthma with Biologics

What is Asthma?

Asthma is a chronic lung condition that is characterized by inflammation and narrowing of the airways. It is commonly referred to as “reactive airway disease” because patients’ airways overreact to different triggers.

What is Severe Asthma?

Severe persistent asthma is characterized by symptoms that persist throughout the day necessitating frequent use of a rescue inhaler. It results in a significant limitation of normal activities and severe impairment of lung function, with pulmonary function testing showing values below 60% of predicted.

Symptoms of Asthma

Shortness of breath, coughing, wheezing, chest tightness, chest pain, chest heaviness, chest squeezing, decreased endurance with activity.

How Do We Diagnose Asthma?

Asthma is diagnosed based on history, physical exam, and pulmonary function testing.

How Do We Treat Severe Asthma?

The first step in treating severe asthma is trying to identify the underlying cause. The most common trigger of Severe Asthma is allergies. Therefore, allergy testing is performed for individuals who have a clinical history of asthma. Other potential causes include Adenoid Hypertrophy, Gastroesophageal Reflux, and Cardiac Disease.

In addition to identifying the underlying cause, we often need medications to decrease airway inflammation. Examples of anti-inflammatory medications include inhaled corticosteroids, leukotriene antagonists, Long-Acting Beta-2 Agonists (LABAs), and Long-Acting Anti-muscarinic agents (LAMAs).

What are the goals of our treatment for patients with Severe Asthma?

1. To have patients simple “feel better” and be able to live healthy active lifestyles.
2. Minimize the incidence of asthma attacks
3. Minimize the chance of airway remodeling (scarring) from chronic airway inflammation.
4. Minimize the adverse effects from use of steroids – both inhaled and systemic (oral and IV).

Biologics have become a key treatment option for Severe Asthma. All Biologics approved for asthma demonstrated a decrease in annualized asthma exacerbation rate compared to placebo in the clinical studies that led to FDA approval.

When considering a biologic treatment for asthma, we first need to obtain laboratory tests to look at “biomarkers.” This essentially means we are looking for specific targets – the cells or proteins that are causing asthma.

Examples of Biomarkers:

• Total serum immunoglobulin E (IGE) – this is an indicator for allergies. IGE initiates the allergic pathway involved in asthma.
• Absolute Eosinophil Count (AEC) – Eosinophils are a type of white blood cell that directly cause airway inflammation. Eosinophils get pulled into airway tissue by multiple triggers – including allergens, infections, and pollutants. Eosinophils then release their chemicals resulting in damage or inflammation of the airway.

Based on one’s clinical history and biomarkers, the physicians at Impact Medical will choose which biologic will most likely help a patient with severe asthma. This means we are not just choosing an asthma medication and hoping it helps, but rather based on one’s lab results, we are choosing a medication with a greater likelihood of helping decrease one’s asthma symptoms and requirement for steroids.

What are examples of Biologics for Asthma?

Omalizumab (Xolair)

Monoclonal antibody that binds to circulating IGE in the bloodstream. This prevents the binding of IGE to the high-affinity IGE Receptor (FcεRI) on the surface of allergy cells (mast cells and basophils), therefore limiting the release of mediators of the allergic response.

Dosing Frequency: Subcutaneous injection every 2-4 weeks

Dupilumab (Dupixent)

Monoclonal antibody that inhibits IL-4 and IL-13 signaling by specifically binding to the IL-4 receptor alpha subunit. This lessens allergic inflammation.

Dosing Frequency: Subcutaneous injection every 2 weeks

Mepolizumab (Nucala)

Monoclonal antibody that specifically targets IL-5 and binds to it. This inhibits IL-5 signaling, reducing the production and survival of eosinophils. Eosinophils are one of the main inflammatory cells involved in allergic inflammation.

Dosing Frequency: Subcutaneous injection every 4 weeks.

Benralizumab (Fasenra)

Antibody that directly binds to the alpha subunit of the IL-5 receptor on eosinophils. This leads to programmed cell death or apoptosis of Eosinophils. Eosinophils are one of the main inflammatory cells involved in allergic inflammation.

Dosing Frequency: Subcutaneous injection every 4 weeks X 3 doses, then every 8 weeks

Tezepelumab-ekko (Tezspire)

Monoclonal antibody that targets a protein called thymic stromal lymphopoietin (TSLP) which is a protein within the Alarmin cytokine family that initiates and perpetuates airway inflammation.

Dosing Frequency: Subcutaneous injection every 4 weeks

If you would like to further discuss asthma treatment options, please schedule an appointment at Impact Medical – Allergy, Asthma and Immunology.