{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:10:18Z","timestamp":1792444218776,"version":"4.5.0"},"reference-count":19,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Type 2 (T2) inflammation plays an important role in the pathogenesis of allergic diseases such as asthma, eosinophilic chronic rhinosinusitis (ECRS), or eosinophilic otitis media (EOM). Currently, in severe asthma with the T2 phenotype, biologics targeting mediators of T2 inflammation dramatically improve the management of severe asthma. While treatment with a single biologic is common, little is known about cases of the sequential use of two biologics. Here, we report a case of severe asthma with refractory ECRS and EOM in which total control of these allergic diseases could not be achieved with a single biologic but could be achieved via the sequential use of the anti-IL-5 receptor antibody and human anti-IL-4\/13 receptor monoclonal antibody. It is suggested that it is necessary to control multiple T2 inflammatory pathways to achieve total control of severe allergic diseases. Sequential biotherapy may help solve the clinical challenges associated with single-agent molecular-targeted therapies.<\/jats:p>","DOI":"10.3390\/biom12040522","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:22:14Z","timestamp":1648675334000},"page":"522","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sequential Biotherapy Targeting IL-5 and IL-4\/13 in Patients with Eosinophilic Asthma with Sinusitis and Otitis Media"],"prefix":"10.3390","volume":"12","author":[{"given":"Ayumi","family":"Chikumoto","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-0450","authenticated-orcid":false,"given":"Keiji","family":"Oishi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5082-1486","authenticated-orcid":false,"given":"Kazuki","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5475-0806","authenticated-orcid":false,"given":"Tsunahiko","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Kakugawa","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Gerontology, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Kanesada","sequence":"additional","affiliation":[{"name":"Nonohana Clinic, Yamaguchi 753-0221, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0514-3241","authenticated-orcid":false,"given":"Kazuto","family":"Matsunaga","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s11882-015-0577-2","article-title":"New Insights into Eosinophilic Otitis Media","volume":"15","author":"Kanazawa","year":"2015","journal-title":"Curr. 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