Dupilumab May Lower Exacerbation Rates in Allergic Bronchopulmonary Aspergillosis

Aspergillus fumigatus
Aspergillus fumigatus
In a post hoc analysis of the LIBERTY ASTHMA QUEST study, researchers found that dupilumab may reduce exacerbations in patients with allergic bronchopulmonary aspergillosis.

This article is part of Pulmonology Advisor‘s coverage of the ACAAI 2019 meeting, taking place in Houston, TX. Our staff will report on medical research related to allergies, asthma, and more conducted by experts in the field. Check back regularly for more news from ACAAI 2019.

HOUSTON — In a post hoc analysis of the LIBERTY ASTHMA QUEST study (ClinicalTrials.gov Identifier: NCT02414854), researchers found that dupilumab reduced the annual number of exacerbations in patients with asthma and serologic evidence of allergic bronchopulmonary aspergillosis (ABPA). The data were presented at the American College of Allergy, Asthma, & Immunology Annual Scientific Meeting 2019 held November 7-11 in Houston, Texas.

The researchers identified 30 patients from the original study cohort who had serologic evidence of ABPA (baseline serum total IgE [immunoglobulin E], >1000 IU/mL, serum IgE-Af (IgE-Aspergillus  fumigatus) >0.35 IU/mL, and blood eosinophils >500 cells/µL). Using negative binomial regression models, the researchers examined annualized severe exacerbation rates during the 52-week treatment period, as well as least square mean change in forced expiratory volume 1 second (FEV1) from baseline to weeks 24 and 52 using mixed-effect models with repeated measures. They also measured total IgE, IgE-Af, and fractional exhaled nitric oxide (FeNO) at week 52 using the Wilcoxon rank-sum test.

Compared with placebo, combined dupilumab 200/300 mg reduced the annualized severe exacerbation rates by 81% (P =.01) and improved prebronchodilator FEV1 by 0.26 L (P =.09) and 0.33 L (P =.07) at weeks 24 and 52, respectively. In addition, dupilumab reduced total IgE, IgE-Af, and FeNO.

The most frequent adverse event reported in either the dupilumab or placebo group was injection site reaction.

Pulmonology Advisor spoke with one of the primary investigators of the analysis, Jonathan Corren, MD, of the David Geffen School of Medicine at the University of California Los Angeles, who commented on the future directions for this therapy, as well as the management of allergic diseases in general.

Editor’s Note: This interview was lightly edited for length and clarity.

Pulmonology Advisor: This was a small study population (N=30). Would you want to see these results replicated in a larger group?

Dr Corren: The post hoc analysis data were strongly suggestive that dupilumab may represent a potential new approach to treating ABPA, but yes, future large clinical trials are needed to confirm what we saw.

Pulmonology Advisor: What about looking at patients with ABPA and cystic fibrosis?

Dr Corren: I would say yes, this is a population that would be worth examining in clinical trials.

Pulmonology Advisor: Are there any plans to examine dupilumab in pediatric patients with ABPA?

Dr Corren: ABPA does typically appear in children with cystic fibrosis. but if it was approved for this indication, it would need to be approved in adults first.

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Pulmonology Advisor: A big theme at this year’s ACAAI meeting appears to be shared decision making. How do you think that fits into your research?

Dr Corren: The first big step with regard to shared decision making and starting a biologic medication or managing a type 2 inflammatory disorder is to decide whether a patient wants to take the big step of starting that medication. We should look at all the possible areas where we could improve: better adherence, proper utilization of therapies, working on home and other environments to deal with allergens, and aggressively addressing comorbidities such as gastroesophageal reflux disease.

Pulmonology Advisor: Has the sensitivity to Aspergillus fumigatus increased in recent years, and if so, could that be the result of climate change?

Dr Corren: The role of climate change in contributing to these type 2 inflammatory diseases is an area of very active investigation, but there are no definitive answers at this time. However, we do know that air pollution is a huge factor because of the changes it causes in the epithelium, and because it can introduce the inflammatory cascade.

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Corren J, Sher L, Zhu X, et al. Dupilumab efficacy in patients with uncontrolled, moderate-to-severe asthma and serologic evidence of allergic bronchopulmonary aspergillosis. Presented at: American College of Allergy, Asthma, & Immunology Annual Scientific Meeting 2019; November 7-11, 2019; Houston, TX. Abstract D201.