Dupilumab increases aspirin tolerance in NSAID-exacerbated respiratory disease

Abstract

Non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) comprises the triad of chronic rhinosinusitis with nasal polyps, asthma, and intolerance to NSAIDs. Dupilumab treatment, targeting the IL-4 receptor alpha, significantly reduces polyp burden as well as asthma symptoms. Here we aimed to investigate the effect of dupilumab on aspirin intolerance, burden of disease, as well as on nasal cytokine profiles in patients suffering from N-ERD. In this open-label trial, adult patients with confirmed N-ERD were treated with dupilumab for six months. Clinical parameters (e.g., total polyp scores, quality of life questionnaires, smell test, spirometry), oral aspirin provocation testing, blood, nasal and urine sampling were monitored up to six months after starting dupilumab therapy at regular intervals. Of the thirty-one patients included in the study, thirty completed both aspirin provocation testing. After six months of treatment with dupilumab, 23.3% (n=7/30) of patients developed complete aspirin tolerance and an additional 33.3% of patients (n=10/30) tolerated higher doses. Polyp burden was significantly reduced (total polyp score: −2.68±1.84, p<0.001) and pulmonary symptoms (asthma control test: +2.34±3.67, p<0.001), as well as olfactory performance improved (UPSIT: +11.16±9.54, p<0.001) in all patients after therapy. Patients with increased aspirin tolerance showed a significant decrease in urine leukotriene E4 levels and their improvement in clinical parameters was associated with the reduction of eotaxin-1, CCL17, IL-5, IL-17A and IL-6. 57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy.

S2k-Leitlinie zur fachärztlichen Diagnostik und Therapie von Asthma 2023

“…Patienten mit Widal-Trias (Samter-Trias) werden jedoch immer häufiger mit Biologika statt mit einer adaptiven Desaktivierung behandelt, v. a. aufgrund der besseren Verträglichkeit und Praktikabilität der Biologika-Therapie, aber auch aufgrund der guten Wirksamkeit der Biologika in dieser Konstellation [73,74]. Nur bei einem Teil der Patienten mit schwerem Asthma und N-ERD werden unter einer Biologika-Therapie COX-1-Hemmer wieder vertragen [75,76]: Dies spricht dafür, dass sowohl die Pathogenese der N-ERD als auch die Wirkung der adaptiven Desaktivierung komplex ist und nicht auf einen singulären Mechanismus zurückzuführen ist [77].…”

The Possible Roles of IL-4/IL-13 in the Development of Eosinophil-Predominant Severe Asthma

“…As for NERD, dupilumab suppresses urinary LTE4 production and improved asthma symptoms in patients with NERD [81]. Furthermore, recent studies have suggested that dupilumab increases aspirin tolerance in patients with NERD [82,83], suggesting that IL-4/IL-13 contributes to the pathogenesis of NERD.…”

Pre-asthma: a useful concept? A EUFOREA paper. Part 2—late onset eosinophilic asthma

“…However, more effective in CRSwNP is treatment with the molecule directed against the IL4R α (dupilumab) ( 103 , 104 ). Dupilumab therapy can also reverse aspirin/NSAID sensitivity, protecting patients against unwonted drug-induced exacerbations ( 97 , 105 ).…”