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 NSAIDs. Patients with AERD often suffer from 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 side effects or short-lived efficacy. In recent years, the emergence of targeted biologics-including anti-IL-5/5Rα (mepolizumab, benralizumab), anti-IgE (omalizumab), anti-IL-4Rα (dupilumab), and anti-TSLP (tezepelumab)-has significantly expanded the treatment landscape for AERD, providing non-surgical 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 NSAID 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 intervention to modify disease progression. While not curative, biologics offer meaningful improvements in quality of life for many patients with AERD. Ongoing research and innovation are essential to realize a future where treatment decisions are guided by precision, accessibility, and sustained disease control.