A new look at how dupilumab treats the symptoms of nasal polyps (CRSwNP) breast rhinosinusitis highlights the potential of the commonly used drug.
A team, led by Claus Bachert, MD, PhD, Ghent University, conducted a post hoc analysis examining the effect of dupilumab across different respondents’ definitions at endpoints reported by patients in a pair of studies testing of efficacy and safety of dupilumab on patients. and CRSwNP.
The data were presented at the 2021 Annual Meeting of the 2021 Academy of Allergy, Asthma & Immunology (AAAAI).
In previous studies, researchers have found that dupilumab resulted in a reduction in nasal polyp score (NPS), as well as individual symptom scores in patients with true CRSwNP. However, researchers have not analyzed respondents using these endpoints.
The Disease
CRSwNP is an inflammatory disease that affects the nasal cavity and paranasal sinuses by predominantly exhibiting type 2 inflammatory pathophysiology. This condition is associated with a high burden of symptoms, including nasal congestion, obstruction, loss of smell, and rhinorrhea, as well as poor health-related quality of life.
Routine treatment includes intranasal corticosteroids, systemic corticosteroids, or sinus surgery. However, these options often do not provide adequate symptom control, with high rates of nasal polyp recurrence and incomplete resolution of loss of sense of smell after surgery.
Previous tests
In a pair of phase 3 trials – SINUS-24 and SINUS-52 – the researchers added dupilumab to routine care and found a significant improvement in endoscopic and radiologic outcomes and symptoms compared with placebo for patients with true CRSwNP.
However, in the respondent analysis, they found even more improvement in both previously unreported termination targets reported by patients.
In SINUS-24, patients were randomized to receive either dupilumab 300 mg subcutaneously every 2 weeks or placebo for 24 weeks. In the second study, patients received either dupilumab 300 mg every 2 weeks to week 52, dupilumab 300 mg every 2 weeks to week 24, then every 4 weeks to week 52, or placebo to week 52.
All patients used mometasone furoate nasal spray during the trials.
Respondent analysis
The investigators sought targeted endpoints for nasal polyp scores and thematic endings of daily symptoms reported by patients of nasal congestion, loss of sense of smell, anterior rhinorrhea, and posterior rhinorrhea scores.
The researchers compared endpoints in the resolution population of dupilumab 300 mg or placebo, as well as for subgroups of patients with asthma, asthma and NSAID-ERD, preoperative surgery, use systemic corticosteroid within the previous 2 years.
Overall, dupilumab led to improvements compared to placebo across different definitions and respondent thresholds, including target and patient-reported endpoints in patients with true CRSwNP, giving included individuals with asthma, NSAID-ERD, prior surgery, or corticosteroid use within the previous 2 years.
“A higher proportion of dupilumab patients versus placebo continued to show an improvement in endpoints reported by patients with more stringent response criteria,” the authors wrote. “These data demonstrate the broad-spectrum treatment effect of double-inhibition of IL-4 and IL-13 with dupilumab on CRSwNP signals. ”
Dupilumab
Dupilumab is a fully human monoclonal antibody VelocImmune that blocks the shared receptor component for IL-4 and IL-13, both known to be major drivers of type 2 inflammation in multiple diseases.
In 2018, the U.S. Food and Drug Administration (FDA) approved dupilumab as an adjunctive maintenance treatment for adults and teens ages 12 years and older, with moderate-to-severe uncontrolled asthma with eosinophilic phenotype or with live corticosteroid-dependent asthma. .
The study, “Respondent analysis to demonstrate the effect of dupilumab treatment over thematic and patient-reported endpoints for patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP),” was published online in AAAAI 21.