Richard Gawel , 2025-06-25 19:57:00
Key takeaways:
- EVEREST represents the first head-to-head study of these biologics for CRSwNP.
- Differences between the biologics were seen as early as 4 weeks.
- Greater improvements in lung function were seen with dupilumab.
Adults on dupilumab for severe chronic rhinosinusitis with nasal polyps had better outcomes than those who used omalizumab, according to an abstract presented at European Academy of Allergy & Clinical Immunology Congress 2025.
Eugenio De Corso, MD, PhD, ENT specialist, otolaryngology, head and neck surgery, rhinology, A. Gemelli University Hospital Foundation, IRCCS, and colleagues called the EVEREST study the first head-to-head, multicenter, randomized, double-blind, phase 4 trial to compare the efficacy and safety of these biologics.
Patients with chronic rhinosinusitis with nasal polyps experienced greater improvements in symptoms with dupilumab compared with placebo, with differences emerging as early as 4 weeks. Image: Adobe Stock
Both biologics have been on the market for CRSwNP and for asthma for several years, De Corso told Healio.
“However, the lack of a head-to-head clinical trial means we haven’t known how they directly compare to each other,” he said. “The goal with EVEREST was to assess how the safety and efficacy of two longstanding respiratory treatments compare.”
De Corso called head-to-head clinical trials the only way to directly compare the efficacy and safety of two drugs, adding that EVEREST is the first such trial evaluating biologics in respiratory diseases.
“The results from head-to-head studies like EVEREST can provide important insights about how available treatment options compare to each other, which can help guide patients and physicians through the treatment decision-making process,” he said.
The study comprised 360 adults (mean age, 51.5 years; 55% men) with severe, uncontrolled CRSwNP and coexisting asthma. Also, 42.5% had coexisting NSAID-exacerbated respiratory disease, and 48.9% had used systemic corticosteroids in the previous 2 years.
Patients received 300 mg of dupilumab (Dupixent; Regeneron, Sanofi) every 2 weeks (n = 181) or a regimen of omalizumab (Xolair; Genentech, Novartis) ranging from 75 mg to 600 mg based on weight and IgE levels every 2 to 4 weeks (n = 179), both for 24 weeks.
“Dupilumab inhibits the signaling of the IL-4 and IL-13 pathways, two key drivers of the type 2 inflammation that is a central underlying driver of CRSwNP,” De Corso said. “Omalizumab works by blocking IgE, which is also involved in type 2 inflammation, but works further downstream of IL-4 and IL-13.”
Patients also used mometasone furoate nasal spray.
“Dupilumab outperformed omalizumab on all endpoints in both CRSwNP and asthma, while showing generally similar safety profiles,” De Corso said.
Compared with omalizumab, dupilumab had a 1.6-point greater reduction in nasal polyp size (P < .0001) and an 8-point greater improvement in ability to identify different smells based on the University of Pennsylvania Smell Identification Test (P < .0001), with more patients surpassing the anosmia threshold, all at 24 weeks.
In fact, the researchers said, differences were seen as early as 4 weeks.
Dupilumab also led to a 0.58-greater reduction in nasal congestion and obstruction (P < .0001); an 0.81-point greater improvement in loss of smell (P < .0001); and a 1.74-point greater reduction in symptom severity (P < .0001), again, all at 24 weeks.
Results at 24 weeks further included a 12.7-point difference in health-related quality of life (P < .0001) based on 22-item Sino-Nasal Outcome Testing or SNOT-22; a 31.27-point difference in peak nasal inspiratory flow (P < .0001); and a 1.87-point difference in overall severity of rhinosinusitis (P < .0001), all favoring dupilumab.
Additional differences included a 150 mL gap in prebronchodilator FEV1 (P = .003) and a 0.48-point gap in seven-item Asthma Control Questionnaire scores (P < .0001), also favoring dupilumab.
The researchers classified dupilumab’s safety results in this study as generally consistent with its known safety profile for approved respiratory indications, including 64% of patients experiencing adverse events, 17.9% with a treatment-emergent adverse event, 2% with serious adverse events, 1.7% with a serious treatment-emergent adverse event and 3% discontinuing treatment due to adverse events.
Similarly, the researchers said, rates for the omalizumab group included 67% with adverse events, 20.8% with treatment-emergent adverse events, 4% with serious adverse events, 4% with a serious treatment-emergent adverse event and 1% who discontinued treatment due to adverse events.
By targeting IL-4 and IL-13, the researchers concluded, dupilumab demonstrated superior outcomes compared with omalizumab for patients with CRSwNP and coexisting asthma.
“These findings further emphasize how addressing IL-4 and IL-14, two key drivers of type 2 inflammation, can improve signs and symptoms of both upper and lower respiratory diseases,” De Corso said.
De Corso also noted how most patients with CRSwNP have asthma as well.
“This study demonstrates that dupilumab can improve particularly challenging signs and symptoms of both diseases, including reducing nasal polyp size and improving sense of smell and lung function compared to another available biologic,” he said.
“These outcomes provide robust clinical data on how two available treatment options compare to each other, which can help clinicians decide on the best treatment option for their patient,” he added.
The researchers will share additional data from the study, which is now complete, as they become available, De Corso said.
