Anti–Interleukin-5 Monoclonal Antibody to Treat Severe Eosinophilic Asthma

Posted by • September 24th, 2014

Most asthma patients who come to your pulmonary office get better. With a regimen of inhaled therapies and possibly a short course of oral corticosteroids, the wheeze and cough and shortness of breath remit. But the patient you are seeing in clinic today is still struggling.

She’s tried every inhaler at its maximum dose and still has been taking oral corticosteroids for more than six months now. Each year, she’s in the hospital at least three times with a severe exacerbation of her symptoms, and an elevated eosinophil count in her peripheral blood. Reaching the limits of your therapeutic armamentarium, you are considering referring her to bronchial thermoplasty but otherwise, you’re not sure what else to offer.

Now, two studies published in this week’s NEJM lend promising evidence to a new therapy that could benefit your patient – a monoclonal antibody, mepolizumab, that targets one aspect of the inflammatory cascade leading to asthma symptoms.

Mepolizumab works by binding to IL-5 – a cytokine that recruits eosinophils from the bone marrow. As blood and sputum eosinophilia correlate with worsened asthma control, it stands to reason that a drug that decreases eosinophilia might improve asthma control. But how to tell which patients with severe asthma might benefit? Initial studies failed to find a benefit across the entire spectrum of those with severe asthma, but smaller studies demonstrated better outcomes in patients with asthma characterized by elevated levels of eosinophils. The pair of studies in this week’s NEJM further characterizes how to administer this drug and to what group of patients.

In one of the studies, Hector Ortega and colleagues enrolled 576 patients with severe asthma. All had more than two exacerbations of their asthma in the prior year despite high dose inhaled corticosteroids, and an elevated blood eosinophil count (≥300cells/µL). Patients were randomly assigned to receive intravenous mepolizumab, subcutaneous mepolizumab or placebo every four weeks, for 32 weeks. They found that both routes of administration decreased frequency of exacerbations by about one-half and improved measures of quality of life and asthma control.

The companion study, by Elisabeth Bel and colleagues, looks specifically at a subset of patients with glucorticoid-dependent severe asthma and persistently elevated eosinophil levels. Patients received monthly subcutaneous mepolizumab or placebo for twenty weeks. Those who were randomly assigned to mepolizumab were able to reduce their glucorticoid dose by fifty percent and – despite the reduced steroid dose – had fewer exacerbations and reported improved asthma control. Both studies showed the drug to have similar adverse event rates to placebo.

In an editorial, Parameswaran Nair, a pulmonologist and asthma researcher, writes that these studies leave open some key questions, specifically whether tracking sputum eosinophil levels might improve drug dosing, and what the most effective route and frequency of administration might be. He also notes that even the placebo group in the Ortega trial saw a significant decrease in exacerbation rates (although the drop was smaller than in those taking the study drug). Perhaps, Nair writes, for some patients, improving adherence might negate the need for a costly therapy like mepolizumab.

Despite these concerns, he notes that anti-interleukin 5 therapy offers “an important advance in our ability to care for patients with severe eosinophilic asthma, particularly as a method of decreasing exacerbations in patients who are dependent on daily use of oral glucocorticoids.” He concludes, “it is reasonable to consider anti–interleukin-5 therapy for patients with severe asthma who are receiving high doses of systemic glucocorticoids and who continue to have an elevated eosinophil count in sputum or blood regardless of their atopic status.”

When it comes to your patient, then, first make sure she’s truly been adherent with her prescribed medications. If she has been, then she will need to wait for regulatory approval as mepolizumab has not been approved for use in asthma.

 

 

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