Aspirin-exacerbated respiratory disease in the era of biologics.

Abstract

Aspirin-exacerbated respiratory disease (AERD) is a chronic, inflammatory syndrome defined by asthma, nasal polyposis, and respiratory sensitivity to cyclooxygenase-1-inhibiting nonsteroidal anti-inflammatory drugs. Patients with AERD often experience severe nasal polyps, frequent sinus surgeries, impaired sense of smell, and persistent asthma. Traditional therapies, including corticosteroids, endoscopic sinus surgery, and aspirin desensitization, have offered symptomatic relief but are often limited by adverse effects or short-lived efficacy. In recent years, the emergence of targeted biologics-including anti-interleukin-5/5Rα (mepolizumab and benralizumab), anti-IgE (omalizumab), anti-interleukin-4Rα (dupilumab), and anti-thymic stromal lymphopoietin (tezepelumab)-has significantly expanded the treatment landscape for AERD, providing nonsurgical options that directly modulate type 2 inflammation and improve both upper and lower airway symptoms. This review synthesizes available data on the efficacy and applicability of each available biologic in AERD, highlighting benefits such as restoration of smell, reduced corticosteroid use, fewer surgical interventions, and potentially diminished nonsteroidal anti-inflammatory drug sensitivity. However, challenges remain. Biologics are costly and not universally accessible, long-term safety data are limited, and no reliable biomarkers currently exist to guide therapeutic selection. Not all patients respond to every agent, underscoring the need for personalized medicine approaches. Future directions include developing predictive biomarkers, conducting head-to-head biologic trials, and exploring earlier biologic interventions to modify disease progression. Although not curative, biologics offer meaningful improvements in the quality of life for many patients with AERD. Ongoing research and innovation are essential to realize a future in which treatment decisions are guided by precision, accessibility, and sustained disease control.