Guy Brusselle, MD, PhD, of Ghent University Hospital.

Guy Brusselle, MD, PhD

The efficacy advantage of dupilumab (Dupixent) over omalizumab (Xolair) in the phase 4 EVEREST trial stems from dupilumab's broader blockade of interleukin (IL)-4 and IL-13 signaling compared with omalizumab's narrower inhibition of immunoglobulin E (IgE), according to investigator Guy Brusselle, MD, PhD, of Ghent University Hospital, who discussed the mechanistic rationale with 

Brusselle presented the latest EVEREST data at the 

European Respiratory Society (ERS) 2026 Congress

EVEREST, a head-to-head phase 4 trial, showed significantly greater rates of composite asthma clinical remission with dupilumab than omalizumab at week 24 in patients with severe 

chronic rhinosinusitis with nasal polyps (CRSwNP)

. The study showed a 24% absolute difference favoring dupilumab.

 Both agents target type 2 inflammatory pathways, yet Brusselle attributed the gap to differences in cytokine targeting rather than to differences in the patient populations enrolled.

"Type 2 inflammation is, of course, heterogeneous, but IgE, immunoglobulin E, is only 1 part of the spectrum of type 2 diseases," Brusselle said.

Dupilumab's IL-4/IL-13 Blockade Drives Efficacy Edge in EVEREST

IL-4 and IL-13 Blockade Versus IgE-Targeted Therapy

Dupilumab blocks the IL-4 receptor alpha subunit shared by IL-4 and IL-13, interrupting signaling from both cytokines simultaneously. One principal effect of IL-4 is inducing immunoglobulin class switching from IgG to IgE in B cells and plasma cells, a pathway already addressed indirectly by omalizumab's anti-IgE mechanism, Brusselle said.

Blocking the IL-4 receptor alpha subunit also interrupts IL-13 effects on airway epithelial cells, reducing mucus production, and on airway smooth muscle cells, limiting bronchoconstriction and helping preserve lung function, according to Brusselle. He said type 2 inflammation in both nasal polyposis and severe asthma extends well beyond IgE alone, and this broader mechanistic reach helps explain why dupilumab outperformed omalizumab across both upper and lower airway outcomes in patients with combined CRSwNP and asthma.

Continued Improvement in Patients Without Asthma Remission

Why does dupilumab outperform omalizumab in EVEREST?


Dupilumab blocks the IL-4 receptor alpha subunit, interrupting both IL-4 and IL-13 signaling, while omalizumab targets IgE alone, a narrower downstream component of type 2 inflammation.

Did patients who did not reach asthma remission still benefit from treatment?


Yes; both remitters and nonremitters showed significant improvement in nasal polyp score and UPSIT scores with dupilumab, reflecting continuous treatment response despite the all-or-nothing remission classification.²

What are the 4 criteria for asthma clinical remission in EVEREST?


Absence of asthma-related exacerbations, no oral corticosteroid use, stable or improved FEV1, and an ACQ-5 score below 1.5, all assessed at week 24.¹

Asthma clinical remission in EVEREST was defined as a composite, all-or-nothing outcome incorporating 4 stringent criteria assessed at week 24: absence of asthma-related exacerbations, no oral corticosteroid use, stable or improved FEV1, and an Asthma Control Questionnaire-5 score < 1.5.¹ Brusselle noted this dichotomous classification does not capture the full extent of treatment response.

Both patients who achieved remission and those who did not showed significant improvement in nasal polyp score and University of Pennsylvania Smell Identification Test (UPSIT) scores with dupilumab (

 <.0001 for both). This reflects a continuous change from baseline rather than a binary outcome, Brusselle explained. A patient can fail just 1 of the 4 remission criteria and still be classified as a nonremitter despite considerable underlying improvement across other asthma and CRSwNP measures, he said.

"He or she has still improved considerably for their asthma, and this is also reflected in the benefits in the upper airways," Brusselle said.

Watch part 1 of our interview with Brusselle here: 

Dupilumab Outperforms Omalizumab for Asthma Remission in Phase 4 EVEREST

De Corso E, Canonica GW, Heffler E, et al. Dupilumab versus omalizumab in patients with chronic rhinosinusitis with nasal polyps and coexisting asthma (EVEREST): a multicentre, randomised, double-blind, head-to-head phase 4 trial. 

Brusselle G, Heffler E, Busse WW, et al. Clinical asthma remission and nasal polyp outcomes over 24 weeks with dupilumab versus omalizumab in patients with severe chronic rhinosinusitis with nasal polyps and uncontrolled asthma: results from EVEREST. Presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

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Guy Brusselle, MD, PhD, explains why broader cytokine blockade with dupilumab outpaced omalizumab, and why nonremitters in EVEREST still improved.

A significantly greater proportion of patients with 

severe chronic rhinosinusitis with nasal polyps (CRSwNP)

 achieved composite asthma clinical remission at week 24 with dupilumab (Dupixent) than with omalizumab (Xolair), according to an analysis of the phase 4 EVEREST trial presented at the 

EVEREST is the first head-to-head trial comparing 2 approved biologics in this overlapping upper and lower airway population.

 Topline efficacy results were published in 

 in December 2025, and the new analysis extends those findings by evaluating a composite asthma remission endpoint incorporating exacerbations, oral corticosteroid (OCS) use, lung function stability, and symptom control.

Guy Brusselle, MD, PhD, of Ghent University Hospital in Belgium, discussed the trial design and findings with 

“Although the active comparator is not [a] placebo but an active treatment, omalizumab, the dupilumab-treated group has a more profound benefit, and the difference between these 2 active treatments is above the MCID, the minimal clinically important difference,” Brusselle said. “So, [these are] very intriguing results.”

Dupilumab Outperforms Omalizumab for Asthma Remission in phase 4 EVEREST

Dupilumab Achieves Greater Asthma Clinical Remission Rates in EVEREST

EVEREST randomized 360 adults with severe CRSwNP and coexisting asthma of any severity 1:1 to subcutaneous dupilumab 300 mg every 2 weeks (n = 181) or weight- and IgE-tiered omalizumab 75-600 mg every 2 or 4 weeks (n = 179) for 24 weeks, on a background of inhaled corticosteroids, intranasal corticosteroids, and a second asthma controller.

 Patients were stratified by type 2 inflammatory status, defined as baseline eosinophils of ≥ 150 cells/µL or fractional exhaled nitric oxide of ≥ 25 ppb. Mean age was 52 years, with a mean 13-year duration of CRSwNP and adult-onset asthma beginning around age 35 years, Bruselle said.

In the prespecified remission analysis, patients were classified by whether they met a composite asthma clinical remission endpoint at week 24, defined as absence of asthma-related exacerbations, no OCS use, stable or improved FEV1 (≤ 5% decline from baseline), and an Asthma Control Questionnaire-5 (ACQ-5) score of ≤ 1.5.

 A significantly greater percentage of dupilumab-treated patients met all 4 criteria compared with omalizumab, at 64% (112 of 175) versus 40.5% (70 of 173) (

Nasal Polyp Score, Smell, and Lung Function Outcomes in EVEREST


EVEREST is a phase 4, head-to-head trial comparing dupilumab and omalizumab in adults with severe CRSwNP and coexisting asthma over 24 weeks, including a composite asthma clinical remission endpoint at week 24.

How did dupilumab compare with omalizumab for asthma clinical remission?


In the week 24 analysis, 64.0% of dupilumab-treated patients met composite asthma clinical remission criteria versus 40.5% of omalizumab-treated patients (

Did nasal polyp and smell outcomes differ by remission status?


No; dupilumab produced greater improvement in nasal polyp score and UPSIT scores than omalizumab regardless of whether patients met asthma clinical remission criteria at week 24.²

Regardless of whether patients met remission criteria, dupilumab produced greater improvement than omalizumab in objective upper airway measures. Bruselle said that nasal polyp score fell by nearly 3 points with dupilumab compared with roughly 1 point with omalizumab at week 24 (P <.0001) University of Pennsylvania Smell Identification Test scores improved to a significantly greater extent with dupilumab as well (

The pattern extended to lower airway outcomes. Dupilumab produced a more pronounced increase in pre-bronchodilator FEV1 than omalizumab, and SNOT-22 scores improved more with dupilumab as well. ACQ-7 scores declined by nearly 2 points with dupilumab versus approximately 1.5 points with omalizumab, with the treatment difference exceeding the minimal clinically important difference for the outcome, Bruselle said.

The full EVEREST dataset, including additional lung function parameters, was presented separately at the 2025 CHEST Annual Meeting, reinforcing dupilumab's comparative benefit across large and small airway outcomes in this population.³ Under the trial's protocol, clinical asthma remission is only confirmed once criteria are sustained through week 52, and longer-term follow-up is anticipated.

Kunzmann K. Dupilumab Bests Omalizumab in Airway Improvement for Patients with CRSwNP and Asthma. HCPLive. 

https://www.hcplive.com/view/dupilumab-bests-omalizumab-airway-improvement-patients-crswnp-asthma

. Published October 22, 2025. Accessed September 11, 2026.

Guy Brusselle, MD, PhD, says that 64% of dupilumab-treated patients met composite asthma clinical remission criteria at week 24 versus 40.5% with omalizumab.

Guy Brusselle, MD, PhD

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