Comparison of Sinonasal Histopathological Changes in Biological Treatment of Eosinophilic Chronic Rhinosinusitis

Comparison of Sinonasal Histopathological Changes in Biological Treatment of Eosinophilic Chronic Rhinosinusitis

Background Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytok...

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Veröffentlicht in:American journal of rhinology & allergy 2022-01, Vol.36 (1), p.72-80
Hauptverfasser: Ho, Jacqueline, Alvarado, Raquel, Rimmer, Janet, Sewell, William A., Walter, Sophie, Earls, Peter, Campbell, Raewyn G., Sacks, Raymond, Kalish, Larry H., Harvey, Richard J
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container_issue 1
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container_title American journal of rhinology & allergy
container_volume 36
creator Ho, Jacqueline
Alvarado, Raquel
Rimmer, Janet
Sewell, William A.
Walter, Sophie
Earls, Peter
Campbell, Raewyn G.
Sacks, Raymond
Kalish, Larry H.
Harvey, Richard J
description Background Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. Methods A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. Results 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p 
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These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. Methods A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. Results 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p &lt; 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p &lt; 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% &gt;10 eosinophils/HPF, τb = −8.47, p &lt; 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = −2.37, p = 0.02). Conclusion Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.</description><identifier>ISSN: 1945-8924</identifier><identifier>EISSN: 1945-8932</identifier><identifier>DOI: 10.1177/19458924211021031</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><ispartof>American journal of rhinology &amp; allergy, 2022-01, Vol.36 (1), p.72-80</ispartof><rights>The Author(s) 2021</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c317t-93a95fa99c6c41bccea8f7f4fe0b6e678e6ff61b3ccb957b5507d6c5e40c2d103</citedby><cites>FETCH-LOGICAL-c317t-93a95fa99c6c41bccea8f7f4fe0b6e678e6ff61b3ccb957b5507d6c5e40c2d103</cites><orcidid>0000-0002-3586-8761 ; 0000-0002-2765-8684</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/19458924211021031$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/19458924211021031$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21819,27924,27925,43621,43622</link.rule.ids></links><search><creatorcontrib>Ho, Jacqueline</creatorcontrib><creatorcontrib>Alvarado, Raquel</creatorcontrib><creatorcontrib>Rimmer, Janet</creatorcontrib><creatorcontrib>Sewell, William A.</creatorcontrib><creatorcontrib>Walter, Sophie</creatorcontrib><creatorcontrib>Earls, Peter</creatorcontrib><creatorcontrib>Campbell, Raewyn G.</creatorcontrib><creatorcontrib>Sacks, Raymond</creatorcontrib><creatorcontrib>Kalish, Larry H.</creatorcontrib><creatorcontrib>Harvey, Richard J</creatorcontrib><title>Comparison of Sinonasal Histopathological Changes in Biological Treatment of Eosinophilic Chronic Rhinosinusitis</title><title>American journal of rhinology &amp; allergy</title><description>Background Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. Methods A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. Results 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p &lt; 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p &lt; 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% &gt;10 eosinophils/HPF, τb = −8.47, p &lt; 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = −2.37, p = 0.02). Conclusion Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. 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These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. Methods A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. Results 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p &lt; 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p &lt; 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% &gt;10 eosinophils/HPF, τb = −8.47, p &lt; 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = −2.37, p = 0.02). Conclusion Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><doi>10.1177/19458924211021031</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3586-8761</orcidid><orcidid>https://orcid.org/0000-0002-2765-8684</orcidid></addata></record>
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title Comparison of Sinonasal Histopathological Changes in Biological Treatment of Eosinophilic Chronic Rhinosinusitis
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