Patients with severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) experienced significantly greater improvements in lung function, asthma control, smell function, and nasal polyp burden with dupilumab than with omalizumab, with the largest benefits seen in those with highly elevated biomarkers of type 2 inflammation.

A post hoc analysis of the phase 4 EVEREST trial found that treatment differences between the two biologics widened progressively as blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels increased, suggesting that these biomarkers may help identify patients most likely to derive substantial benefit from dupilumab.

“We know that these biomarkers provide synergistic information regarding type 2 inflammation and risk of severe asthma attacks,” said Michael E. Wechsler, MD, professor of medicine and director of the Cohen Family Asthma Institute at National Jewish Health in Denver.

Wechsler presented the findings at the European Academy of Allergy and Clinical Immunology (EAACI) 2026 Annual Congress.

Shared Type 2 Inflammation

Patients with CRSwNP frequently have coexisting asthma, and both conditions are driven by overlapping type 2 inflammatory pathways. Elevated blood eosinophil counts and FeNO levels have emerged as clinically useful biomarkers and treatable traits in asthma management because they are associated with increased disease burden and a greater risk for exacerbations.

Both dupilumab and omalizumab are approved for the treatment of moderate-to-severe asthma and inadequately controlled CRSwNP, but they target different components of the inflammatory cascade. Dupilumab blocks signaling through interleukin (IL)-4 and IL-13, two key drivers of type 2 inflammation, whereas omalizumab targets immunoglobulin E (IgE).

The current analysis was based on EVEREST, the first randomized head-to-head trial comparing biologics in respiratory disease. The study enrolled 360 adults with severe CRSwNP and uncontrolled asthma despite treatment with nasal corticosteroids, inhaled corticosteroids, and additional controller therapy. Participants were randomly assigned to receive 300 mg add-on dupilumab every 2 weeks or omalizumab according to approved dosing regimens for 24 weeks.

Treatment Effect Increased With Biomarker Levels

Investigators examined outcomes in the overall intention-to-treat population and in subgroups with increasingly elevated biomarkers, defined by eosinophil counts of at least 300 cells/µL combined with FeNO thresholds of at least 20, 35, or 50 parts per billion (ppb).

Across all analyses, dupilumab consistently outperformed omalizumab. For lung function, measured by pre-bronchodilator forced expiratory volume in 1 second, dupilumab produced an additional 0.15-L improvement compared with omalizumab in the overall study population (P < .01). However, the treatment difference increased to 0.21 L among patients with eosinophils ≥ 300 cells/µL and FeNO ≥ 20 ppb, 0.22 L among those with FeNO ≥ 35 ppb, and 0.30 L among those with FeNO ≥ 50 ppb (P < .01 for all).

A similar pattern emerged for nasal polyp burden. Compared with omalizumab, dupilumab improved nasal polyp scores by 1.6 points in the overall population (P < .0001). The treatment difference increased progressively to 1.8, 1.9, and 2.1 points, respectively, in the increasingly elevated biomarker subgroups (P < .0001 for all).

The greatest improvements were observed in what Wechsler described during his presentation as the “hot-hot” group, that is, patients with eosinophil counts of at least 300 cells/µL and FeNO levels > 50 ppb.

Improvements Extended Beyond Lung Function

Benefits extended beyond airway function and nasal polyp size. Patients receiving dupilumab also experienced greater improvements in smell identification, measured using the University of Pennsylvania Smell Identification Test. Treatment differences increased from 8.0 points in the overall study population (P < .001) to 9.0 points in patients with the highest biomarker levels (P < .0001).

Asthma control also improved progressively with increasing biomarker burden. Compared with omalizumab, dupilumab improved Asthma Control Questionnaire-7 (ACQ-7) scores by 0.48 points in the overall study population (P < .001), rising to 0.66 points in patients with eosinophils ≥ 300 cells/µL and FeNO ≥ 50 ppb (P < .0001 for all). Lower ACQ-7 scores indicate better asthma control.

Biologically Plausible Explanation for Dupilumab Results

The findings suggest that patients with the highest levels of inflammation are most likely to benefit from dupilumab.

“[Which] makes sense because of how IL-4 and IL-13 work,” Wechsler replied. “You’re blocking IL-4-mediated IgE production, IL-13-mediated nitric oxide production, and IL-4/IL-13-mediated trafficking of eosinophils,” he said. “It makes sense that in those patients who have the highest biomarkers, you’re most likely to have greater efficacy using a drug like dupilumab.”

The findings add to growing evidence supporting biomarker-guided biologic selection in severe asthma and related type 2 inflammatory diseases. Rather than asking whether biologics work, clinicians are increasingly focused on determining which biologic is most likely to benefit an individual patient.

“The present analysis suggests that patients with both elevated eosinophils and elevated FeNO may represent a subgroup particularly likely to respond to IL-4/IL-13 blockade,” said Wechsler.

Whether these findings should directly influence biologic selection in routine practice remains uncertain and will require prospective validation.

EVEREST was sponsored by Sanofi and Regeneron Pharmaceuticals. Several co-authors reported being employees of the sponsoring companies. Wechsler reported having consulting, advisory, speaking, or research relationships with numerous pharmaceutical companies involved in asthma therapeutics, including AstraZeneca, Amgen, GlaxoSmithKline, Regeneron Pharmaceuticals, Sanofi, and others.