Dupilumab An Option When Other Targeted Agents Fail In Aspirin-Exacerbated Respiratory Disease

Dupilumab, a monoclonal antibody targeting interleukin-4 (IL-4) receptor alpha, should be considered in patients with aspirin-exacerbated respiratory disease (AERD) whose symptoms are not adequately controlled by monoclonal antibodies targeting the IL-5 pathway, clinicians from Boston say based on their clinical experience.

"AERD, the triad of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and respiratory reactions to cyclooxygenase-1 inhibitors, is characterized by difficult-to-treat upper and lower respiratory symptoms," they note in a paper in the Journal of Allergy and Clinical Immunology: In Practice.

The IL-4 receptor alpha inhibitor dupilumab is approved in the U.S. for moderate-to-severe eosinophilic asthma and inadequately controlled CRSwNP and has shown efficacy for upper and lower airway symptoms in AERD.

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Dr. Kathleen M. Buchheit of Brigham and Women's Hospital, Harvard Medical School and colleagues reviewed the charts of 41 patients with AERD enrolled in the BWH AERD registry; 38 were treated with mepolizumab, one with reslizumab and two with benralizumab; 27 patients subsequently transitioned to dupilumab for inadequately controlled upper and/or lower respiratory symptoms, and 14 continued with mepolizumab.

According to the researchers, all patients with inadequate response to the IL-5 pathway inhibitors mepolizumab, benralizumab, or reslizumab had "significant improvements" in upper and lower airway symptoms and reductions in asthma exacerbations after transitioning to dupilumab.

Patients who mounted a satisfactory response to mepolizumab and continued on the drug reported improvements in upper- and lower-airway symptoms with mepolizumab.

The researchers say their study also points to the "possibility of different AERD endotypes, which may be partially driven by specific type 2 cytokines."

"While the availability of respiratory biologic medications has broadened treatment options for AERD patients, limited data exists to guide biologic selection. To our knowledge, this is the first comparison of monoclonal antibodies targeting IL-5/IL-5R-alpha and IL-4R-alpha in patients with AERD," the researchers say.

The retrospective nature of the study and small number of patients are limitations of the analysis.

"Nonetheless, in this real-world setting, we found that AERD patients who failed to improve with mepolizumab, benralizumab, or reslizumab had improvements in asthma control, nasal congestion and anosmia, and reduced asthma exacerbations during subsequent dupilumab treatment. Clinicians should consider dupilumab for AERD patients with inadequate response to anti-IL-5/IL-5R-alpha therapy," Dr. Buchheit and colleagues conclude.

"Head-to-head, prospective studies of respiratory biologics for AERD patients would allow for further identification of the responder endotype to guide selection of appropriate biologic therapy," they add.

Support for the study was provided by the National Institutes of Health and by generous contributions from the Vinik and Kaye Families. Dr. Buchheit has served on scientific advisory boards for AstraZeneca and GlaxoSmithKline.

—Reuters Staff

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