A post hoc analysis of two phase 3 trials identified that as many as 95% of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) had type 2 inflammatory signatures depending on the definition of inflammation used.
Up to 95% of patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) have type 2 (T2) inflammatory signatures, according to pooled data from two trials. The results were published in the International Forum of Allergy & Rhinology.
CRSwNP causes nasal congestion, loss of smell, and anterior and posterior rhinorrea. Approximately one-fifth of patients with CRS have nasal polyps, which are benign growths in the nasal cavities and tend to be present in both sides of the nasal cavitiy.
Researchers from the United States and Europe conducted a post hoc analysis of the SINUS-24 and SINUS-52 trials. These trials were multicenter, randomized, double-blind, placebo-controlled phase 3 trials. This post hoc analysis evaluated patients with severe CRSwNP who received Dupixent (dupilumab) 300 mg once every 2 weeks or placebo.
Dupixent blocks interleukin (IL)-4 and IL-13, which are key drivers of T2 inflammation. The post hoc analysis reviewed multiple proposed definitions to assess the prevalence of T2 inflammation and how effective Dupixent was according to each definition of T2 inflammation.
The post hoc analysis included multiple subgroups: patients enrolled from Japan/Asia, patients without coexisting asthma, patients with low eosinophil count, and patients with low immunoglobulin E (IgE) levels.
There were six definitions of T2 inflammation:
A total of 724 patients were included and at baseline between 62.2% to 95.3% had a T2 inflammatory signature depending on the definition used. Only 4.7% of patients did not meet any of the T2 inflammatory criteria. Patients from Japan/Asia had similar T2 inflammation prevalences as those in the broader population.
Outcomes assessed in the analysis included nasal polyp score, nasal congestion, loss of smell, 22-item Sino-Nasal Outcome Test total score, Lund-MacKay computed tomography score, and the University of Pennsylvania Smell Identification Test score.
The researchers found at weeks 24 and 52, across all six definitions of T2 inflammation that:
Patients who did not meet T2 inflammation criteria still saw greater changes from baseline with Dupixent versus placebo at weeks 24 and 52, but there was variability across the six definitions.
The researchers noted that the findings may not be generalizable to the wider population of patients with CRSwNP due to the fact that SINUS-24 and SINUS-52 had strict eligibility criteria.
“Dupilumab, which blocks the action of T2 cytokines, demonstrated efficacy across T2 definitions in this cohort, suggesting that it could be an effective therapeutic option for the majority of patients with uncontrolled CRSwNP,” the authors concluded.
A previous post hoc analysis of SINUS-24 and SINUS-52 found that Dupixent reduced symptom burden in this group of patients. These results were presented in October 2022 at the AMCP Nexus meeting. After 52 weeks on Dupixent, patients had a mean number of 2.1 days with severe nasal congestion compared with 6.7 days for patients on placebo. At baseline, patients had a mean number of 14.8 days with severe nasal congestion.
In addition, patients on Dupixent had a mean number of 19.2 days with no or mild nasal congestion compared with only 6.9 days for patients on placebo.