Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs). Although high-dose aspirin therapy after desensitization (ATAD) and surgery are effective, adverse effects and high dropout rates limit its use. The emergence of biologics for asthma and/or CRSwNP entails rethinking the management of AERD. There is no consensus on choosing between ATAD and biologics. This systematic review evaluates current evidence on the role of biologics in the management of AERD, focusing on their potential to induce NSAID tolerance and proposing a management algorithm. A systematic literature search was conducted across PubMed, Embase, and Scopus up to March 2025. Studies were selected based on predefined criteria, excluding editorials, reviews, case reports, guidelines, and publications not in English. Data were extracted from clinical trials, real-world studies, and retrospective analyses. The various inflammatory pathways targeted by biologics included immunoglobulin E (omalizumab), subunit alpha of the interleukin 4 receptor (IL-4Ra) (dupilumab), IL-5/IL-5Ra (mepolizumab, benralizumab), and thymic stromal lymphopoietin (tezepelumab). These drugs have demonstrated efficacy in improving asthma and CRSwNP in AERD. The most consistent evidence seems to favor omalizumab and dupilumab for enhancing tolerance to NSAIDs. Although evidence remains inconclusive, the combination of ATAD and biologics may offer additive benefits in selected patients. Biologics represent a promising alternative in the management of AERD, particularly for patients with poor tolerance to aspirin. Further prospective, controlled studies are needed to define optimal treatment algorithms and identify biomarkers predictive of therapeutic response.
Keywords: ATAD; Aspirin-exacerbated respiratory disease (AERD); Biological therapies; Desensitization; Dupilumab; Mepolizumab; NSAID hypersensitivity; Omalizumab.