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

Abstract

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 < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τb = −8.47, p < 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.

Tissue Eosinophilia is Superior to an Analysis by Polyp Status for the Chronic Rhinosinusitis Transcriptome: An RNA Study

“…In the absence of a universally acceptable standardized tissue eosinophil cut-off count, 10 we used 10/hpf as it is one of the most widely described criteria in published literature. [11][12][13][14][15] Soler et al 16 used absolute tissue eosinophil counts until they defined the cut-off point with the largest absolute difference in disease-specific quality of life scores and smallest p-value, which was identified at ≥10 eos/hpf. However, few transcriptomic studies have compared eCRS and neCRS, [17][18][19][20][21][22][23] and these studies have been based on Asian populations only.…”

“…We studied the transcriptomic signatures of CRS based on its phenotype (CRSwNP and CRSsNP) and endotype (<10 eos/hpf and > 10 eos/hpf) by whole tissue RNA‐Seq. In the absence of a universally acceptable standardized tissue eosinophil cut‐off count, 10 we used 10/hpf as it is one of the most widely described criteria in published literature 11–15 . Soler et al 16 used absolute tissue eosinophil counts until they defined the cut‐off point with the largest absolute difference in disease‐specific quality of life scores and smallest p ‐value, which was identified at ≥10 eos/hpf.…”

Histopathologic features of biologic therapy nonresponders in chronic rhinosinusitis with nasal polyposis

“…3 Ho et al demonstrated that sinonasal tissue of patients with eosinophilic chronic rhinosinusitis (eCRS) treated with mepolizumab had predominately eosinophilic inflammation despite biologic therapy and more severe subepithelial edema while patients treated with benralizumab had predominate lymphoplasmacytic inflammation. 14 No study to date has identified histopathologic changes produced by dupilumab. The purpose of this study is to determine the histopathologic features in patients with CRSwNP who underwent FESS following failure of biologic therapy.…”

RELIght: A two‐year REal‐LIfe study of mepolizumab in patients with severe eosinophilic asTHma in Greece: Evaluating the multiple components of response

“…Representative studies using prospective and/or retrospective data have previously confirmed the higher rate of responders compared with those of super responders. 4,5 One possible limitation is the fact that only those patients who continue with mepolizumab are analyzed at 24 months, leading to a "selection-bias", because patients who continue therapy are presumably those who experience greater improvement.…”