Choosing the Optimal Biologic for Severe Asthma

Nicholas J. Gross, MD, PhD


April 09, 2018

In most asthmatic patients, the disease can be controlled by a corticosteroid with the addition of a beta-agonist if necessary; however, a small number of patients are still symptomatic and liable to have exacerbations despite these modalities.

We now have biologic agents, including the anti-immunoglobulin (Ig) E monoclonal antibody omalizumab (Xolair®), that may be able to control asthma in patients who do not adequately respond to the optimal use of conventional therapies. What is the recommended care pathway to use for any of these agents? A recent authoritative statement[1] provides an answer.

Clearly, one must ensure that the asthmatic patient has used all of the recommended medications before embarking on a novel and expensive medication.

If the asthma still is poorly controlled and the patient is having exacerbations, the first step is to determine whether the asthma is associated with allergens and an elevated blood IgE level. If both are high, a trial of omalizumab should be instituted. The dose is determined by IgE level and body weight.[2] Omalizumab is approved in adults and children older than 6 years and is given by subcutaneous injection every 2-4 weeks.[1] If this is therapeutically effective, it can be continued. If not and exacerbations are not eliminated or substantially diminished, one of the other biologic agents that address eosinophils should be given.

If the initial investigation reveals the presence of eosinophilia, one can start with an anti-interleukin (IL)-5 antibody biologic agent.

Mepolizumab (Nucala®) is an agent that addresses and inactivates the IL-5 component of eosinophilia. It may take many weeks to become fully active. One trial[3] randomly assigned patients to receive one of three doses of intravenous mepolizumab (75 mg, 250 mg, or 750 mg); a 52% reduction in clinically significant exacerbations after 52 weeks was reported for the highest dose. When effective, its use may enable a cautious reduction in corticosteroid administration. It should not be used to address an acute exacerbation of asthma. Side effects include headache, back pain, and fatigue.

Other biological agents that address "difficult asthma" are available.

Benralizumab (FasenraTM), also an anti-IL-5 agent, reduces exacerbations at about the same amount as mepolizumab and has been reported to enable a 75% reduction in corticosteroid use.[4]

Dupilumab inhibits IL-4 and IL-13 and shows evidence for improving severe asthma that resists conventional management.[5] It has yet to be approved by the US Food and Drug Administration for asthma.

None of the above agents address the needs of an acute exacerbation. Rather, they require long-term administration, and it may be many weeks before any improvements are seen. Their safety appears to be relatively good—but, like all novel agents, side effects may yet appear.

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