Treatment with tezepelumab, an anti-TSLP antibody, for otitis media with ANCA-associated vasculitis comorbid with asthma: A case report

We report a case in which tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) antibody, was effective for otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) comorbid with asthma and chronic rhinosinusitis (CRS) due to eosinophilic granulomatosis with polyangiitis (EGPA). The patient was a 42-year-old man with severe asthma and peripheral blood eosinophilia. Dupilumab, an anti-interleukin-4 (IL-4) receptor alpha antibody, was first used to treat his asthma. Thereafter, he developed myeloperoxidase specific (MPO)-ANCA positive EGPA. Hence, glucocorticoid (GC) administration was commenced, and mepolizumab, an anti-IL-5 antibody, was introduced, leading to sustained remission for 15 months. After gradually tapering off the GC, he developed bilateral CRS, for which endoscopic sinus surgery (ESS) was performed. After mepolizumab was tapered, the respiratory symptoms flared up again, along with left-sided hearing loss, earache, and otorrhea, which was diagnosed as OMAAV. The treatment was switched to benralizumab, an anti-IL-5 receptor antibody. However, as the GC was gradually tapered, serum MPO-ANCA levels increased again, with relapse of coughing and shortness of breath. Hence, the treatment was switched to tezepelumab. Immediately thereafter, his MPO-ANCA level became negative, and the various symptoms, including OMAAV, CRS, and respiratory symptoms, improved, with sustained remission despite tapering of GC. • This is the first report of the efficacy of tezepelumab for refractory asthma, OMAAV, and CRS associated with EGPA. Our patient had been treated with multiple biologics (dupilumab, mepolizumab, and benralizumab) and eventually, after the introduction of tezepelumab, MPO-ANCA levels became negative, airway symptoms, OMAAV, and CRS improved, and remission was maintained while tapering off steroids. • TSLP is a cytokine secreted by the airway epithelial cells in response to viral infection or allergen exposure. Eosinophils, basophils, and mast cells express TSLP receptors and may be directly activated by TSLP. Genetic evaluations have shown an association between EGPA and the TSLP gene. • Tezepelumab may be a therapeutic option for selected cases of OMAAV associated with eosinophilic inflammation, such as those linked to EGPA.