Biologic Therapies: A Systematic Review of the Indications, Efficacy, Safety, and Outcomes in Ear, Nose, and Throat Diseases

Biologic therapies, such as omalizumab, mepolizumab, and dupilumab, are novel therapeutic agents that offer a targeted approach for managing chronic inflammatory and immune-mediated ear, nose, and throat (ENT) conditions. However, the indications, efficacy, and adverse events of these medications in various ENT disorders have not been studied before. Therefore, this systematic review was performed to evaluate their indications, clinical efficacy, and safety in ENT management. A systematic search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across five major databases: PubMed, Embase, Cochrane Library, Medline, and Web of Science. Studies published between 2015 and May 2025 were considered, and additional manual searches and reference screening were also performed. Eligible studies included those written in English, assessing biologics in ENT diseases, and reporting on at least one of the following outcomes: clinical efficacy, safety, or indications. The study characteristics, population details, medications used, and outcomes were assessed. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool, with disagreements resolved by a senior assessor. A total of 497 records were identified, and after screening and quality assessment, 10 trials involving 2,406 patients were included. The primary indication of biologics use across nine studies was chronic rhinosinusitis with nasal polyps (CRSwNP), while one study assessed allergic rhinitis. Most trials compared biologics to a placebo, except one study that evaluated mepolizumab in combination with functional endoscopic sinus surgery. Biologics consistently demonstrated clinically significant reductions in endoscopic nasal polyp scores (P<0.05) and improvements in Visual Analogue Scale (P<0.05), SinoNasal Outcome Test (P<0.05), and olfactory function (P<0.001). Imaging findings (Lund-Mackay scores) were also in favor of biologics (P<0.05). Furthermore, biologics were associated with reduced need for repeat surgery (mepolizumab), lower serum immunoglobulin E (IgE) levels (dupilumab), and better productivity and quality of life (omalizumab). The safety profile was favorable, with nasopharyngitis (4-47%), headache (7-25%), and injection-site reactions (6-40%) being the most common adverse events, while no fatal events were reported (0%). In summary, biologics improved clinical symptoms, nasal polyp scores, olfaction, and quality of life in ENT conditions, particularly CRSwNP and allergic rhinitis, with favorable safety profiles and additional benefits, including reduced need for surgery and lower IgE levels.