Dupilumab Provides Sustained Control of Eosinophilic Otitis Media Through Suppression of Type 2 Inflammation: A Long-Term Cohort Study With Molecular Profiling of Middle Ear Effusion

AIM: To evaluate the long-term clinical efficacy of dupilumab and elucidate its mechanism of action by analyzing local and systemic cytokine profiles in patients with severe eosinophilic otitis media (EOM). BACKGROUND: Long-term treatment outcomes and underlying molecular mechanisms for EOM, an intractable inflammatory disease, remain poorly understood. METHODS: In this prospective, single-center study, we enrolled 25 patients with severe EOM who received dupilumab for up to 3 years and 54 controls who received standard care. We assessed clinical parameters, including the EOM severity score, and performed comprehensive cytokine profiling on middle ear effusion (MEE) and serum samples collected at baseline and after treatment. RESULTS: Dupilumab treatment resulted in a rapid and sustained reduction in the EOM severity score (mean, 7.0 to 0.8) and temporal bone CT scores (8.0 to 1.9) over 3 years, whereas the control group showed no improvement. Molecular analysis revealed that dupilumab potently suppressed local inflammation, markedly reducing interleukin (IL)-4, IL-13, and eotaxin levels in the MEE. In contrast, systemic cytokine changes in serum were minimal. Baseline K-means clustering identified 3 distinct molecular endotypes of EOM, with 1 cluster characterized by a dominant type 2 inflammatory signature (high IL-4 and IL-13) that strongly aligned with the mechanism of action of dupilumab. CONCLUSIONS: Dupilumab provides effective and durable long-term control of severe EOM and coexisting sinus disease by potently suppressing localized type-2 inflammation. Identification of distinct molecular endotypes supports a personalized medicine approach for EOM. Hence, dupilumab may be a valuable long-term, tissue-preserving treatment for refractory EOM.