Dupilumab improves aspirin tolerance in NSAID-exacerbated respiratory disease

Following 6 months of dupilumab treatment, 57% of patients with NSAID-exacerbated respiratory disease had higher aspirin tolerance than before treatment, according to study results published in European Respiratory Journal.

These patients also had better smell perception and disease-specific quality-of-life measures, according to researchers.

“We demonstrated that treatment with dupilumab in [NSAID-exacerbated respiratory disease (N-ERD)] patients leads to a significant reduction in polyp size accompanied by an improvement in quality of life and smell perception,” Sven Schneider, MD, PhD, of the department of otorhinolaryngology at Vienna General Hospital and Medical University of Vienna, and colleagues wrote.

In a prospective, open-label, single-center trial, Schneider and colleagues analyzed 30 adults with N-ERD — which is characterized by the presence of chronic rhinosinusitis with nasal polyps, asthma and aspirin intolerance — to see how dupilumab (Dupixent; Sanofi, Regeneron) treatment for 6 months changed their aspirin tolerance, disease burden and nasal cytokine profiles.

Researchers assessed patients’ total polyp scores, quality of life, smell tests and spirometry throughout the duration of dupilumab therapy. They also conducted two oral aspirin provocation tests and collected blood, nasal and urine samples.

At the baseline provocation test, 61% of patients experienced upper and lower respiratory tract symptoms, 32% had isolated upper respiratory tract symptoms, and 6% had isolated lower respiratory tract symptoms. Most patients showed symptoms at a 125 mg dose.

After 6 months of dupilumab treatment, 23.3% of patients had complete aspirin tolerance, tolerating a cumulative dose of 875 mg (P < .001) during the second provocation test, and 33.3% patients had a tolerance for higher aspirin doses, according to researchers.

In terms of intolerance, 40% of patients showed symptoms at the same amount of aspirin from baseline, and one patient even tolerated less aspirin. Researchers noted that most of these symptoms were isolated upper respiratory tract reactions, with only six patients experiencing both upper and lower respiratory tract reactions after 6 months.

Researchers also observed significant declines in polyp burden (total polyp score, –2.68 ± 1.84), improved asthma symptoms related to quality of life (asthma control test, 2.34 ± 3.67) and improved smell perception using the University of Pennsylvania Smell Identification Test (11.16 ± 9.54; P < .001 for all).

Researchers reported improvement in Total Nasal Symptom Scores (–3.46 ± 3.36) and Sino-Nasal Outcome Test-22 (–26.73 ± 23.49; P < .001 for both).

Of the 33 various inflammatory biomarkers studied, patients showed reduced eotaxin-3 and interleukin (IL)-5 in nasal secretions, according to researchers.

Among those with a tolerance for higher aspirin doses, researchers found a significant reduction in urine leukotriene E4 levels. Further, improved polyp scores, quality of life questionnaires, smell tests and spirometry were linked to decreased eotaxin-1, CCL17, IL-5, IL-17A and IL-6 in these patients.

Additionally, researchers noted that a link between decreases in CCL17 and IL-5 and better smell perception among patients becoming tolerant to aspirin, suggesting that improved smell after receiving dupilumab can possibly be explained by two factors: decreased polyp size or decreased biomarker levels in nasal secretions.

“As dupilumab-induced aspirin tolerance was not achieved in all patients, aspirin challenge is recommended prior to NSAID prescription to determine status of sensitivity in N-ERD patients receiving dupilumab,” Schneider and colleagues wrote. “Although the development of aspirin tolerance led to a significant reduction in urine-derived arachidonic acid metabolites involved in N-ERD, biomarkers clearly identifying patients who will respond with aspirin tolerance to different biologicals are still missing and warrant further investigation.”