Eosinophilic Asthma Severe but Now More Manageable

Eosinophilic asthma is a type of asthma characterized by an excess of specialized white blood cells called eosinophils in the airways. Classifying asthma is tricky, however, and there is a considerable amount of overlap of the eosinophilic phenotype with type 2 inflammation and atopic inflammation characterized by airway inflammation and mucus production. As a result, some patients with asthma may need multiple treatment modalities.

Waqas Ahmad, M.D., a family physician who runs the medical advisory board of Insurecast, a life and health insurance agency, says patients with eosinophilic asthma suffer from more frequent and more severe asthma attacks. Ahmad notes that eosinophilic asthma is quite rare, accounting for about 5% of all asthma cases and 50% to 60% of severe asthma cases. Acute eosinophilic asthma, which requires systemic corticosteroids or biologics, probably accounts for between 2% and 4% of all asthma cases, according to the American Partnership for Eosinophilic Disorders.

People with eosinophilic asthma tend to have developed asthma at a younger age — often in childhood — than those with other types of asthma, according to Marc C. Gauthier, M.D., assistant professor of medicine in the Division of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh School of Medicine.

Although there are several theories regarding allergen triggers, not all patients with eosinophilic asthma have allergies, and it’s not entirely understood why eosinophilic asthma occurs. Some studies suggest some people are genetically predisposed to developing the condition after being exposed to certain viruses in childhood.

“In general, once established, these patients have persistent inappropriate eosinophil response in the airways,” Gauthier says. “What maintains this inflammation is unclear.”

Treatment strategies

Treating patients with eosinophilic asthma revolves around inflammation control and eosinophil inhibition. “This is generally achieved with corticosteroids,” Gauthier says. “For many patients, inhaled steroids, when used consistently, are able to effectively suppress eosinophilic inflammation in the lungs. For patients who require additional treatment, systemic corticosteroids or biologic agents targeted toward eosinophils may be needed.” Bronchodilators such as albuterol are usually not effective as single-agent therapy because they do not address the underlying eosinophilic inflammation.

High-dose, short-acting inhaled corticosteroids may be combined with the inhaled form of long-acting beta-agonists, Ahmad says. When they are not effective, doctors may prescribe systematic corticosteroids, he says. The leukotriene modifiers Accolate (zafirlukast), Singulair (montelukast) and Zyflo (zileuton) also can be helpful, Ahmad says.

For patients with type 2 overlapping inflammation, treatment with Dupixent (dupilumab) is an option. Dupixent is an antibody against the interleukin-4 receptor alpha subunit that blocks both interleukin-4 and interleukin-13 signaling. It quells airway inflammation and reduces the production of mucus.

“For patients with atopy, drugs targeted to mast cells — montelukast against the leukotriene receptor or zileuton against the 5-lipoxygenase enzyme — may be helpful,” Gauthier says. “Allergen avoidance may also be of significant benefit, or [introducing] allergen immunotherapy in patients with mild to moderate disease.”

Additionally, for patients with severe disease or extrapulmonary manifestations, systemic treatment with corticosteroids or immune suppression may be needed — even with biologic therapy.

“The introduction of biologics in the last five years for eosinophilic asthma has dramatically changed the approach for therapy options,” Gauthier says. “Many patients who previously were hospitalized multiple times per year or had frequent emergency department or urgent care visits are now able to stay out of the hospital altogether on therapy. Many have had a significant improvement in their lung function and quality of life. Many patients who had to rely on systemic corticosteroids for years have been able to drastically reduce their dose or wean off steroids completely.”

Three choices

There are three biologics that directly target eosinophilic asthma via the interleukin-5 (IL-5) pathway. Nucala (mepolizumab) is an
anti-IL-5 antibody that directly binds IL-5, thereby preventing it from activating eosinophils. “This is a fixed-dose, once-a-month injection and can be given either in the [physician’s] office or at home,” Gauthier says. “The dose was designed to avoid complete elimination of eosinophils, but as a result this can lead to a slight underdose in some patients.”

Cinqair (reslizumab) is also an anti-IL-5 antibody that directly binds to IL-5, preventing it from activating eosinophils. It has weight-based dosing, which results in a slightly better efficacy anecdotally in larger patients, according to Gauthier. Some patients say that the effect of the drug, which is administered intravenously, can wear off prior to the next infusion, Gauthier adds.

Fasenra (benralizumab) is an antibody that directly binds to the IL-5 receptor on the surface of eosinophils. It is administered as an injection in the upper arm, thigh or abdomen, and Gauthier says there are formulations that can be delivered with a home injector.

All three of the antibody treatments tend to be more effective in people with higher eosinophil counts, Gauthier says.

Payel Gupta, M.D., FACAAI, an associate clinical professor at SUNY Downstate Medical Center in Brooklyn and Mount Sinai Health System in New York City and a volunteer for the American Lung Association, notes that for people with moderate to severe asthma who have not found relief with other therapies, biologics can help keep them out of the hospital and off oral steroid medications, which pose risks. The side effects vary, and some people are bothered by injections. On the other hand, the biologics space out treatment, and Fasenra and Nucala can be administered by the patient at home. Of course, insurance coverage is a factor, “Biologics are usually covered by insurance if a patient meets all the necessary criteria for approval, so they should not cost too much out of pocket for the patient,” Gupta says. But without coverage, they are not going to be a choice for most patients because of the expense.

Future research into eosinophilic asthma will examine whether other factors play a role in the disease. “Better understanding of the processes behind airway remodeling, exacerbations and overlapping inflammation will help us better understand this phenotype and develop additional therapies for patients who have incomplete responses to the current options,” Gauthier says.

Keith Loria is a freelance writer in the Washington, D.C., and a regular contributor to Managed Healthcare Executive®.