Short-Term Efficacy of Biologics in Recalcitrant AFRS: A Systematic Review and Meta-Analysis

CLINICAL QUESTION

Do biologic therapies improve symptoms, endoscopic findings, and inflammatory markers in patients with recalcitrant allergic fungal rhinosinusitis (AFRS)?

BOTTOM LINE

Biologic therapy—including dupilumab, mepolizumab, and omalizumab—significantly improved SNOT-22 scores, endoscopic scores, serum eosinophil counts, and total IgE levels in patients with refractory AFRS across six studies (60 patients). No adverse events, additional surgeries, or systemic corticosteroid requirements were reported during short-term follow-up (three to 14 months).

BACKGROUND: AFRS is a sub-type of chronic rhinosinusitis driven by type I and type III IgE-mediated hypersensitivity to fungal antigens. Despite endoscopic sinus surgery and post-operative steroid regimens, many patients experience persistent or recurrent disease. Given AFRS’s strong type 2 inflammatory signature, biologics used in chronic rhinosinusitis with nasal polyps (CRSwNP)—such as dupilumab, mepolizumab, and omalizumab—may offer therapeutic benefit, though specific evidence for AFRS has been limited.

STUDY DESIGN: Systematic review and meta-analysis of retrospective and prospective studies evaluating biologic therapy for refractory AFRS. Databases were searched through November 2024. Eligible studies included biologic treatment with quantifiable pre-treatment and post-treatment outcomes (SNOT-22, endoscopic scores, serum eosinophils, total IgE). Follow-up ranged from three to 14 months.

SETTING: International review, including studies from Canada, Saudi Arabia, Thailand, and Korea

SYNOPSIS: The review included 60 patients who received biologics after failing conventional medical and surgical management. Across all biologics, treatment resulted in significant improvements in patient-reported outcomes, endoscopic appearance, and inflammatory laboratory markers. SNOT-22 scores improved substantially, reflecting reductions in nasal obstruction, facial pressure, and overall symptom burden. Endoscopic scores demonstrated less mucosal edema, reduced allergic mucin, and improved sinus cavity appearance. Biologic therapy also led to decreases in serum eosinophil counts and total IgE levels, consistent with suppression of type 2 inflammatory pathways. Dupilumab—an inhibitor of IL-4 and IL-13 signaling—produced the broadest improvements across clinical and laboratory domains. Mepolizumab effectively reduced eosinophil counts and improved symptoms, while omalizumab improved symptoms and endoscopic findings but showed limited short-term reduction in total IgE. Importantly, none of the studies reported serious adverse effects, additional surgeries, or systemic corticosteroid requirements during follow-up. Limitations included small sample sizes, short follow-up durations, and heterogeneity across study methods and biologic types. Despite these limitations, the findings suggest biologics may be a valuable therapeutic option in recalcitrant AFRS, particularly for patients seeking to minimize systemic steroid exposure.

CITATION: Im YH, et al. Short-term efficacy of biologics in recalcitrant allergic fungal rhinosinusitis: a systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2025;173:840-847. doi: 10.1002/ohn.1339.

COMMENT: AFRS can be a challenging condition to treat with recurrence. Treatment typically relies on well-performed endoscopic sinus surgery, removal of fungal elements and inspissated secretions, and the delivery of topical corticosteroids in high-volume irrigations, often with the need for oral corticosteroids in cases of recurrence. The approval data for biologic medications specifically excluded these patients; however, this meta-analysis finds that in patients with refractory AFRS, biologics can provide significant benefit in those who have failed routine medical therapy. These medications may offer an additional option for these patients, who traditionally needed to have repeated courses of oral corticosteroids and/or revision surgeries for management of their disease.—Ashoke Khanwalkar, MD.