Dupilumab as Add-on Therapy for Chronic Rhinosinusitis With Nasal Polyposis in Aspirin Exacerbated Respiratory Disease

Abstract

Background Aspirin-exacerbated respiratory disease (AERD) affects 7% of asthmatics. Usual therapies are inadequate for asthma and/or nasal polyposis, leading to decreased quality of life. Objective Our objective was to evaluate the efficacy of dupilumab in AERD patients with uncontrolled, chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods Patients 18 years and older with a physician diagnosis of AERD and sino-nasal outcome test 22 (SNOT 22) score ≥19 despite standard medical therapy were eligible for the study. Patients received one month of placebo dosing, followed by 6 months of dupilumab. Patients were blinded to the order of therapy. Wilcoxon-paired rank sum test was used to compare study outcomes at baseline and the completion of the study. Results Ten patients completed the study. The median baseline SNOT 22 score improved from 46 [IQR: 34 to 64.8] to 9.5 [IQR: 2.5 to 19] after 6 months of therapy (p = 0.0050). The median baseline Lund MacKay score improved from 21.5 [IQR: 17 to 23.3] to 4 [IQR: 1.2 to 6] after 6 months of therapy (p = 0.0050). There was also improvement in the following secondary outcomes: asthma control test (ACT), mini asthma quality of life questionnaire (AQLQ), and University of Pennsylvania Smell Identification test (UPSIT). Exhaled nitric oxide (FeNO), total serum IgE, 24-hour urinary leukotriene E4, and serum thymus and activation regulated cytokine (TARC) also decreased. There were no significant study-related adverse events. Conclusion Dupilumab was highly effective as add-on therapy for CRSwNP in AERD, improving patient-reported outcomes, sinus opacification, and markers of T2 inflammation.

Management of Non-steroidal Anti-inflammatory Drug-exacerbated Respiratory Disease

“…53 In 2020, Mustafa et al followed 10 patients with AERD treated with placebo for 1 month, followed by dupilumab as add-on therapy for 6 months. 19 In addition to improved SNOT-22 and Lund-MacKay computed tomography scores, most patients also had improved tolerance to alcohol, a result which was reproduced in a separate case series. 54 While omalizumab (anti-IgE) has been approved by the FDA for asthma and idiopathic urticaria since 2003, in December 2020, it joined dupilumab as the only other FDA-approved biologic for nasal polyps.…”

“…Importantly, patients often tolerate alcohol after aspirin desensitization or dupilumab therapy. 18,19 This unique aspect of therapy may be a motivating factor for some patients to undergo these treatments.…”

Simultaneous treatment of Samter triad and prurigo nodularis with dupilumab

“…Ten patients were treated for 6 months and showed improvement in both SNOT and asthma measures. 9 Several case reports and case series have also shown effectiveness of dupilumab for the treatment of PN. One study found that dupilumab treatment led to a reduction of the Numeric Rating Scale Itch Intensity to 0 in 4 patients with recalcitrant PN.…”

Eicosanoid dysregulation and type 2 inflammation in AERD

“…Because type 2 biomarkers such as IgE, IL-5, IL-4, and IL-13 play a critical role in the asthma and CRSwNP pathogenesis, the use of new biologics (dupilumab, omalizumab, mepolizumab, benralizumab) inhibiting these type 2 targets represents a new rational approach. Some of these biologics have recently shown induction of NSAID tolerance (omalizumab) 9 and reduction of biosynthesis of CysLTs monitored as decreased urinary LTE 4 (omalizumab, dupilumab) 9,10 in patients with AERD. The first trials in patients with severe and uncontrolled CRSwNP are encouraging because they suggest a better response in patients with AERD.…”