Eosinophilic Asthma Resource Centre

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Roundtable: Targeted therapy in the management of severe asthma patients

Speakers: Prof. Roland Buhl (Mainz, Germany), Prof. William Busse (Madison, WI, USA), Prof. Ian Pavord (Oxford, UK)

Roundtable: Targeted therapy in the management of severe asthma patients

In this roundtable discussion Prof. Buhl, Prof. Busse, and Prof. Pavord discuss the daily management of severe asthma, the current challenges in severe asthma treatment, and emerging targeted therapies.

Summary

The goals of this roundtable discussion are to recognise the challenges in severe asthma management, to explain how management is changing with new targeted therapies, and to describe key factors for selecting patients for targeted therapy.

Severe asthma is a complex condition that cannot be controlled despite high-intensity treatment. It can include recurrent asthma attacks, poor symptom control, poor lung function or a combination of the three.

It is important to ask your patients what problems they are having as some patients may adjust their lifestyle to compensate for their disease. It is also important to correctly diagnose severe asthma and to attempt to address any comorbidities contributing to symptoms.

Exacerbations in severe asthma are those events that cannot be treated using rescue medication, but are usually treated using corticosteroids. The level of control is indicated by the number of refills of rescue medication or the number of times corticosteroids have been prescribed. A high frequency of exacerbations can lead to irreversible loss of lung function and lack of treatment response.

Diagnosing severe asthma involves evaluating symptoms and onset, doing lung function tests, allergy tests and other tests to determine the endotype/pathophysiology to individualise targeted therapy.

 It is important to determine the mechanism of disease as it guides treatment selection. The profs discuss differentiating between eosinophilic and T2-high inflammation and T2-low asthma to administer the correct therapies.

The eosinophilic phenotype is characterised by: severe disease, often late onset, that is unresponsive to treatment, compromised lung function and sense of taste and smell, elevated exhaled NO, elevated eosinophils and often allergenic.

Eosinophilic asthma patients are often caught in a cycle of physician visit – corticosteroid therapy – improvement – tapering of steroids – relapse and return to physician. These patients are taking high doses of steroids, LABAs and prednisone/prednisolone.  They require referral to a specialist to explore other treatment options due to significant morbidity associated with oral steroid use.

Biologics, such as omalizumab, mepolizumab, reslizumab and benrazilumab may offer benefits for this asthma subpopulation. Patients should be told that the biologics offer a new option that is injected once a month. They have a favourable side-effect profile, but they are not necessarily going to be the solution that eliminates severe asthma overnight. The patients must continue to take existing medications and be evaluated after 2-3 months, whereby dose reductions of those medications may take place.

IL-5 therapies are most effective in patients with an eosinophil count >500 who have nasal polyps. Treatment can improve lung function, asthma symptoms and quality of life.

Response to IL-5 is measured by a drop in eosinophils, an effect on lung function, positive effects on sleep and steroid intake and return of taste/smell (in patients with nasal polyps). If response is observed, then oral steroids can be titrated down. If no response, then discontinue the biologic and monitor the patient.

The role of eosinophils in asthma is not clearly understood, but when the number of eosinophils decreases, the disease improves.

There is much work to be done in the subset of asthma patients with T2-low asthma. They are less likely to be atopic, have no eosinophils and low FeNO. Steroids are not beneficial and may do more harm and anti-IL-5 and anti-IgE treatment is not effective. New treatment options are needed for these patients.