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

• Published in: International forum of allergy & rhinology Vol. 14; no. 5; pp. 939 - 949
• Main Authors: Baird, Ali M., Masliah, Jamie, Filip, Peter, Talati, Vidit, Brown, Hannah J., Owen, Grant, Khalife, Sarah, Papagiannopoulos, Peter, Gattuso, Paolo, Batra, Pete S., Tajudeen, Bobby A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-05-2024
• Subjects: Adult; Antibodies, Monoclonal, Humanized - therapeutic use; Basement membranes; biologic therapy; Biological products; Biological Products - therapeutic use; Biological Therapy; Chronic Disease; chronic rhinosinusitis; Comorbidity; Endoscopy; endotypes; Eosinophilia; Female; Humans; Immunoglobulin E; Leukocytes (eosinophilic); Male; Middle Aged; Monoclonal antibodies; nasal polyps; Nasal Polyps - drug therapy; Polyposis; Polyps; Retrospective Studies; Rhinosinusitis; Rhinosinusitis - drug therapy; structured histopathology; endotypes; chronic rhinosinusitis; nasal polyps; biologic therapy; structured histopathology
• ISSN: 2042-6976; 2042-6984
• DOI: 10.1002/alr.23283

Background
Biologics are effective for chronic rhinosinusitis with nasal polyposis (CRSwNP) by reducing type 2 inflammation. Nonresponders often require functional endoscopic sinus surgery (FESS) and represent a challenging population potentially due to non‐type 2 pathophysiology. This study characterizes the histopathologic features of biologic nonresponders.
Methods
A retrospective review of 257 CRSwNP patients undergoing FESS was conducted. The biologic nonresponder group included patients with prior biologic therapy who exhibited persistent symptoms and polyp burden. Those with CRSwNP not prescribed biologic therapy were selected as controls. Demographics, comorbidities, and structured histopathology consisting of 13 variables were collected.
Results
Of 257 CRSwNP patients, 20 were on biologics prior to FESS. Fourteen patients (70.0%) received dupilumab, one (5.0%) received mepolizumab, one (5.0%) received omalizumab, and four (20.0%) tried multiple biologics. The mean age for the biologic nonresponder group was 45.8 years compared to 50.4 years for the controls. Nonresponders had a significantly increased incidence of reduced tissue eosinophilia, defined as <5 per high power field (55% vs. 31.2%, p = 0.044) and increased basement membrane thickening (100% vs. 78.1%, p = 0.019). The remaining 11 variables did not reach statistical significance.
Conclusion
Histopathologic analysis of biologic nonresponders demonstrates decreased eosinophilia and thickened basement membranes. These findings, particularly low tissue eosinophils, are consistent with a non‐type 2 CRSwNP that may be recalcitrant to biologic therapies. Histopathologic analysis done in conjunction with FESS may aid clinicians in understanding response to biologic therapies in patients with CRSwNP who have persistent symptom burden necessitating FESS.