Aspirin tolerance in the majority of patients with non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is increased with dupilumab, according to study findings published in the European Respiratory Journal.
Researchers sought to assess how dupilumab affected patients with N-ERD with respect to aspirin tolerance, disease burden, and nasal cytokines. The primary outcome was the proportion of patients developing tolerance to aspirin after a 24-week treatment; secondary endpoints were the effect of dupilumab on polyp size, asthma, and quality of life.
The researchers conducted a prospective open-label single-center trial (ClinicalTrials.gov Identifier: NCT04442256) at the Department of Otorhinolaryngology and the Department of Dermatology at the Medical University of Vienna, Austria. The trial included 31 adult patients with N-ERD who were treated with dupilumab for 6 months (subcutaneous, 300 mg biweekly after loading dose of 600 mg). Patients were monitored using oral aspirin testing; blood, nasal, and urine sampling; smell test; spirometry; total polyp scores; and quality of life questionnaires.
Among the participants, 30 completed the aspirin provocation testing at baseline and at 24 weeks. At baseline, 19 patients presented both upper (nasal congestion, rhino conjunctivitis or rhinorrhea) and lower respiratory tract symptoms (coughing, pulmonary obstruction, or dyspnea); 10 patients showed isolated upper respiratory tract symptoms; and 2 patients showed only lower respiratory tract reactions.
After 6 months of dupilumab treatment, researchers found that 7 patients developed complete aspirin tolerance; 10 patients tolerated higher doses of aspirin; 12 patients exhibited symptoms at the same dosage; and 1 patient tolerated less aspirin. Researchers also found that 6 patients experienced both upper and lower respiratory tract symptoms, and 16 patients experienced mainly isolated upper respiratory tract reactions.
In this single-center prospective open-label study, we demonstrated that treatment with dupilumab in N-ERD patients leads to a significant reduction in polyp size accompanied by an improvement in quality of life and smell perception.
Total polyp score indicated mean (SD) polyp size was significantly reduced (-2.68 [1.84]; P <.001) in all patients after treatment. They noted olfactory performance improved (University of Pennsylvania Smell Identification Test [UPSIT], 11.16 [9.54]; P <.001). Pulmonary symptoms improved (asthma control test, 2.34 [3.67]; P <.001). Total Nasal Symptom Score improved (-3.46 [3.39]; P <.001) as did Sino-Nasal Outcome Test-22 levels (-26.73 [23.49]; P <.001).
Among the 17/30 patients (57%) with increased aspirin tolerance, there was a significant decrease in urine leukotriene E4 levels. Reduction of eotaxin-1, CCL17, interleukin (IL)-5, IL-17A, and IL-6 was associated with patient improvement in clinical parameters.
Significant study limitations include underpowered sample size and lack of a placebo control group.
“In this single-center prospective open-label study, we demonstrated that treatment with dupilumab in N-ERD patients leads to a significant reduction in polyp size accompanied by an improvement in quality of life and smell perception,” concluded researchers. Additionally, they stressed, “57% of N-ERD patients tolerated higher doses of aspirin under dupilumab therapy.”
Disclosure: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.