Dupilumab Improves Lung Function, Reduces Exacerbations in Allergic, Non-Allergic Asthma

Nicola Hanania, MD

Describe the Phase 3 Liberty Asthma Quest study of dupilumab.

For physicians treating patients with asthma, why is it important to have dupilumab as an additional treatment option?

In an abstract released at the annual meeting of the American College of Asthma, Allergy and Immunology in Seattle, Washington, investigators found that add-on dupilumab (Dupixent, Sanofi/Regeneron) reduced severe asthma exacerbations and improved lung function in patients with allergic and non-allergic uncontrolled, moderate-to-severe asthma and was generally well tolerated. In an interview with MD Magazine, study co-author Nicola Alexander Hanania, MD, a pulmonologist at the Baylor College of Medicine in Houston, Texas, explained what the study means for practicing pulmonologists and allergists.This was an analysis of the large Quest Liberty study, which was the large 1900-patient study looking at patients with severe asthma and the effect of the aisle 4 receptor antagonist dupilumab in these patients. This abstract looks at the allergic subpopulation in the large study population. the main study was published in the New England Journal of Medicine, so this is a subgroup analysis. We looked at patients who had allergic asthma, defined by the presence of allergy specific IgE in the blood (one or more positive), and high serum ige -- that’s how we defined the population. We found in this population that about 56% of the patients had allergic phenotypes, which was shown in the large study. Looking at dupilumab, even though it's approved for eosinophilic asthma in the United States, it actually works very well in patients with allergic phenotypes, so that's really the take home messageWhen it comes to severe asthma, we have overlapping phenotypes. Some severe asthmatics have eosinophilic asthma and they don't have allergic symptoms and they're not sensitized. For those, we have several drugs currently approved, including the anti-aisle 5 therapies. Dupilumab will work with that as well.

What we also have is another phenotype that doesn't have very high eosinophils, but they have allergic asthma, which is characterized by sensitization to allergens and high IgE. Right now we have a treatment which is an anti-IgE, which is omalizumab, which has been approved for a long time for that population. What dupilumab does is it actually can target those populations, the eosinophilic and also allergic. It is an aisle 4 receptor antagonist that can block the IgE synthesis, and therefore it does work nicely in allergic asthma by reducing the production of IgE.

What are the best practices for prescribing dupilumab?

Coming back to clinicians, I think there's obviously overlap between all the biologics available, but knowing where each drug will work will help them identify the best treatment for the patient. So it’s mainly about improving the personalized approach to therapy, keeping in mind that there's going to be overlap between eosinophilic and allergic asthma in real life. Some patients with allergic asthma also have eosinophilic asthma, but knowing that the drug works in both populations is reassuring.This is true for all biologics, not just to dupilumab -- before we jump into describing a biologic one has to determine whether the patient that we are dealing with has severe disease. By definition, severe disease is in patients with asthma who require a high dose of inhaled corticosteroids, plus another controller like a long-acting beta2-agonist to maintain control, without which the pt is uncontrolled. So severe disease is all those patients who continue to be uncontrolled despite that therapy. Another very important group is those who are still dependent -- more than 50% that group with severe asthma.

This should be underlined: We have to rule out good adherence, comorbidities management, and chiggers. Because you may get patients who need all these medications because they're not taking their inhaler correctly or they're not taking their medication, or they’re continuously exposed to chiggers, or they have comorbidities. But if all these are dealt with and the patient is still needing inhaled steroids at a high dose to keep the asthma under control, then that’s severe asthma. That's when you need to biologic.