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EVEREST: Dupilumab Outperforms Omalizumab in Head-to-Head CRSwNP Trial, with Anju Peters, MD
Peters emphasized how the new findings reinforce treatment strategies for chronic rhinosinusitis with nasal polyps.
The treatment landscape for chronic rhinosinusitis with nasal polyps (CRSwNP) has changed rapidly in recent years with the introduction of biologic therapies, but questions about optimal sequencing and comparative efficacy still remain. The phase 4 EVEREST trial (EValuating trEatment RESponses of dupilumab versus omalizumab) represents the first direct, head-to-head comparison of 2 biologics for CRSwNP, comparing dupilumab, which blocks interleukin (IL)-4 and IL-13 signaling, and omalizumab, which targets immunoglobulin E (IgE). Updated data from EVEREST were presented at the 2025 European Respiratory Society (ERS) Congress in Amsterdam from September 27 to October 1 and continue to inform treatment strategies for patients with severe CRSwNP and other comorbidities.
In EVEREST, patients with severe, uncontrolled CRSwNP, defined by a nasal polyp score ≥5 and persistent congestion and smell loss, were randomized to receive dupilumab or omalizumab for 24 weeks, alongside standard intranasal corticosteroids. Results demonstrated that dupilumab was superior to omalizumab across all primary and secondary endpoints, including NP size reduction, smell restoration, and improvements in patient-reported symptoms. The findings reinforce earlier indirect comparisons and meta-analyses suggesting greater efficacy of IL-4/IL-13 blockade in CRSwNP, while confirming both agents’ well-established safety profiles.
HCPLive spoke with Anju Peters, MD, professor of medicine and director of Clinical Research in the Division of Allergy and Immunology at Northwestern University Feinberg School of Medicine, about the significance of EVEREST and what the results mean for clinicians managing CRSwNP. Peters explains how the trial provides long-awaited comparative clarity between dupilumab and omalizumab, highlights which patient factors may influence treatment selection, and reflects on the next steps for biologic research in chronic sinus disease, particularly in defining remission and investigating why dupilumab shows unique efficacy for restoring smell.
"CRSwNP really affects quality of life. It is often a comorbidity of asthma, especially severe asthma, and CRS often drives asthma exacerbations. These patients end up getting oral steroids, end up getting surgery, and prior to the biologics, got repeated surgeries. So these biologics have changed how we manage CRSwNP. And this is a unique study that did a head to head comparison. Both biologics were safe in this study and are safe. Both biologics showed efficacy, but dupilumab was superior to omalizumab. So I do think it helps guide us in clinical care as to then deciding which biologic to use," Peters said.
Peters' disclosures include AstraZeneca, Sanofi, and Regeneron.
