Does Dupilumab Improve Sinonasal Outcomes in AERD Patients?

BACKGROUND

Aspirin-exacerbated respiratory disease (AERD) is a chronic inflammatory condition characterized by asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and hypersensitivity to aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). It significantly affects patients’ quality of life with symptoms such as nasal congestion, anosmia, and recurrent polyp formation. Patients with AERD are at an increased risk of disease recurrence following functional endoscopic sinus surgery (FESS), often requiring additional interventions beyond topical and oral corticosteroids.

Historically, aspirin therapy after desensitization (ATAD) has been the primary long-term treatment option to reduce recurrence. However, its use is limited by challenges such as patient noncompliance, gastrointestinal intolerance, and the risk of anaphylaxis. As AERD is recognized as a form of type 2 inflammation, dupilumab has emerged as an adjunctive treatment option. Dupilumab is a human monoclonal antibody that inhibits interleukin IL-4 and IL-13 signaling. These cytokines play a key role in driving type 2 inflammation, the primary mechanism underlying CRSwNP and AERD pathophysiology. By blocking this pathway, dupilumab has been shown to reduce nasal polyp burden, improve sense of smell, and decrease the need for systemic corticosteroids in CRSwNP, including AERD.

The efficacy of dupilumab has been well documented in general CRSwNP populations. However, its specific impact on AERD patients, particularly those who have undergone prior FESS, warrants further exploration. This Best Practice review synthesizes evidence from five key clinical trials to evaluate whether dupilumab improves sinonasal outcomes in this challenging patient population.

BEST PRACTICE

Despite limited randomized trials specific to AERD, the consistent improvements in sinonasal outcomes across studies strongly support dupilumab as an effective treatment for AERD patients post-FESS. It significantly reduces nasal polyp burden, improves olfactory function, and enhances patient-reported outcomes with a favorable safety profile. Dupilumab also decreases the need for systemic corticosteroids and revision surgeries, making it a promising maintenance therapy for this challenging population.

Future studies should focus on longer follow-up periods, larger AERD populations, and comparisons to ATAD to validate dupilumab’s efficacy and cost-effectiveness in real-world settings.