Will an Immunomodulator Help Your Asthma?

Nurse giving immunomodulator injection to patient
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An immunomodulator is a class of asthma medication that is indicated for patients with difficult-to-control asthma. As an add-on therapy for your asthma, an immunomodulator is a controller medication rather than a short acting medication for the acute relief of asthma symptoms. For the nearly one-third of asthmatic patients who either do not respond to inhaled steroids or have a poor response, an immunomodulator may offer some hope for better asthma control.

Xolair, a monoclonal antibody, is the only currently approved immunomodulator therapy available for asthma. This immunomodulator is appropriate for moderate persistent or severe persistent asthma patients with:

  • A positive skin test or other blood test indicating an allergy to a known asthma trigger, such as dust mites, dog, cat or cockroach dander.
  • Symptoms that are inadequately controlled with inhaled corticosteroids.

The other immunomodulator commonly used in allergy and immunology practices today is Cinryze, a treatment for a recurring swelling in the face and neck called hereditary angioedema.

How Immunomodulators Work

Immunomodulators decrease both asthma symptoms and the need for systemic corticosteroids. Needing systemic corticosteroids more than twice per year is a sign of poor asthma control. Immunomodulators can also decrease inflammation by impacting a number of different places in the pathophysiology of asthma, including:

An immunomodulator binds to IgE and prevents it from binding to basophils and mast cells. Additionally, an immunomodulator decreases the number of circulating basophils and prevents mast cells from releasing substances that will make your symptoms worse.

How Immunomodulators Help

An immunomodulator is sometimes referred to as a steroid-sparing drug that improves airway and lung function. Additionally, an immunomodulator will decrease asthma symptoms such as:

Treatment with an immunomodulator has been associated with a decreased frequency of asthma exacerbations and emergency room visits as well as improvements in lung function and quality of life. Generally, an immunomodulator will not replace other asthma treatment, but will be added to it. The addition of an immunomodulator has been associated with as much as a 25 percent decrease in steroid use.

Potential Side Effects

While your immunomodulator should be well tolerated, there are a number of common side effects and uncommon side effects to be aware of, including:

  • Urticaria and anaphylactic reactions—Urticaria, or hives, is an allergic reaction that can have serious consequences if not treated promptly and appropriately. Your doctor will require you to be monitored for a period of time in the office after each injection. While most reactions occur within one to two hours after one of the initial injections, allergic reactions have occurred after many injections and many hours since receiving the injection.
  • Cancer—While not totally clear at this point, cancers were more common among patients receiving Xolair. However, the reason why this relationship between cancer and the immunomodulator was seen is not yet totally understood.
  • Injection site pain—As with any injection, pain at the injection site is a known side effect and may occur in up to 20 percent of patients receiving an immunomodulator.
  • Upper respiratory tract infections—Make sure you discuss with your doctor what to do and when it is appropriate to seek care if you experience these symptoms.
  • A sore throat and headache—If these symptoms do not resolve with conservative measures, like fluid and over-the-counter pain medication, then you should talk with your doctor.

    Immunomodulators in Development

    A number of other immunomodulators targeting different stages of the pathogenesis of asthma are in the pipeline:

    • Daclizumab is a monoclonal antibody that impacts a number of places in the asthma cascade. It has been tested in a clinical trial of 115 asthma patients, but demonstrated only small improvements in lung function and asthma control.
    • Lebrikizumab is a human monoclonal antibody that binds to and blocks interleukin-13 activity, another component of the pathophysiology of asthma. Two clinical trials, VERSE and LUTE, demonstrated a decreased rate of asthma exacerbations and improved lung function in patients (with no significant safety concerns) with moderate-to-severe asthma who have poor control despite optimized current standard-of-care treatment. Patients most noted to benefit in these studies had high levels of periostin, a protein known to increase levels of inflammation.
    • Reslizumab is a humanized monoclonal antibody targeting interleukin-5 (IL-5). In clinical trials, it has been used in adult and adolescent asthma patients with elevated blood eosinophils, despite an inhaled corticosteroid based regimen. Reslizumab demonstrated decreased asthma exacerbation and improved lung function in phase III clinical trials in more than 1,700 adolescent and adult patients. Based on the trials, it is expected that the indications will be similar to that of Xolair. Reslizumab is being looked at by the FDA and TEVA took action on their application back in 2016. Several other drug companies, such as AstraZeneca, have similar drugs in their pipelines, too.
    • Eculizumab (Soliris®) is a humanized monoclonal antibody targeting the complement system and is currently approved by the FDA for the treatment of paroxysmal nocturnal hemoglobinuria. A small clinical trial demonstrated improvements in lung function and allergic symptoms. However, this drug has been associated with life-threatening and fatal meningococcal infections. As a result, the drug is restricted and doctors need to register to be able to prescribe it. 
    • Suplatast has shown positive results as well, but the three times per day dosing leaves concerns about asthma compliance.
    • Tumor necrosis factor-alpha (TNF-α) is an immunomodulator that also acts in several places in the pathophysiology of asthma. Other than improved control in a series of overweight asthma patients (a known condition leading to TNF-α overexpression), TNF-α has not decreased exacerbations or improved lung function. More specifically, Infliximab (Remicade®) and etanercept (Enbrel®) are immunomodulators currently used for other diseases, such as rheumatoid arthritis. These drugs are associated with increased risks of infection.
    • Peroxisome proliferator activated receptor-gamma (PPAR-γ) is another class of medication under study. These drugs are already being used in the treatment of diabetes, where it was discovered that they had potential anti-inflammatory actions. Guinea pigs treated with rosiglitazone specifically were found to have significant decreases in blood levels of IL-5 and IgE. When the animals were euthanized, tIL-5 and IgE were also found to be decreased in the lungs. This lead investigators to assume that it might be a useful asthma treatment, too.
    • Syk kinase is an intracellular protein tyrosine kinase that prevents degranulation of mast cells. The drug was found to decrease nasal congestion and discharge, sneezing, itching of the nose and throat, post-nasal drip, cough, headache, and facial pain in patients undergoing allergic rhinitis in a lab setting. A study using an inhaled formulation is planned for asthma patients.


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