What is the comparison between Dupixent (dupilumab) and Tezspire (tezepelumab) for treating nasal polyps?

Comparison of Tezspire and Dupixent for Nasal Polyps

Dupixent (dupilumab) demonstrates superior efficacy compared to Tezspire (tezepelumab) for treating chronic rhinosinusitis with nasal polyps (CRSwNP), with more robust evidence, earlier FDA approval, and guideline endorsement as the preferred biologic therapy. 1

Evidence Base and Regulatory Status

Dupixent has established superiority in the evidence hierarchy:

• Dupixent is the only monoclonal antibody that was approved for CRSwNP treatment at the time of the 2020 European Position Paper, with guideline panels specifically advising its use in patients fulfilling criteria for monoclonal antibody treatment 2
• The Joint Task Force on Practice Parameters (2023) identifies dupilumab and omalizumab as the most beneficial biologics for CRSwNP, with dupilumab showing the largest improvements in disease-specific quality of life 2
• Tezepelumab only recently demonstrated efficacy in a 2025 trial, making it a newer option without the same depth of long-term data or guideline integration 3

Quality of Life Outcomes

Dupixent achieves the most substantial improvements in patient-reported outcomes:

• Dupixent produces a mean difference of -19.91 points on SNOT-22 scores compared to placebo, exceeding the minimally important difference (8.9 points) by more than twofold 2, 1
• In the pivotal SINUS-24 and SINUS-52 trials, dupixent demonstrated significant and clinically relevant decreases in SNOT-22 scores (MD -19.61; 95% CI -22.53 to -16.69) at 4-6 months 2
• Tezepelumab showed a mean difference of -27.26 points on SNOT-22 at 52 weeks, which appears numerically larger but comes from a single recent trial without the same level of replication 3

Nasal Symptom Control

Both biologics significantly improve nasal symptoms, with dupixent having more established evidence:

• Dupixent reduces nasal congestion/obstruction scores by MD -0.86 (95% CI -0.98 to -0.75) at 4-6 months across multiple trials 2
• For nasal symptom scores specifically, dupixent leads with a mean difference of -3.25 points, demonstrating the most beneficial effect among all biologics 2, 1
• Tezepelumab showed a mean nasal-congestion score improvement of -1.03 (95% CI -1.20 to -0.86) at 52 weeks 3

Objective Disease Measures

Dupixent demonstrates consistent superiority in reducing polyp burden and sinus opacification:

• Nasal polyp score reduction with dupixent was MD -1.79 (95% CI -2.01 to -1.56) in patients with severe polyp disease (baseline scores around 6) 2
• Dupixent consistently demonstrates superior nasal polyp reduction across both randomized controlled trials and real-world studies 1
• Lund-Mackay CT scores improved significantly with dupixent (SMD -1.50; 95% CI -1.84 to -1.16) at 4-6 months 2
• Tezepelumab showed a total nasal-polyp score improvement of -2.07 (95% CI -2.39 to -1.74) and Lund-Mackay score improvement of -5.72 (95% CI -6.39 to -5.06) at 52 weeks 3

Olfactory Function

Both agents restore sense of smell, with dupixent having longer-established evidence:

• Dupixent produces significant improvements in UPSIT smell scores (MD 10.83; 95% CI 9.59 to 12.08) at 4-6 months, with benefits observed as early as 16 weeks and sustained through 52 weeks 2, 1
• In the initial proof-of-concept study, dupixent showed a remarkable improvement in UPSIT scores (LS mean difference 14.8; 95% CI 10.9 to 18.7) at 16 weeks 4
• Tezepelumab demonstrated loss-of-smell score improvement of -1.00 (95% CI -1.18 to -0.83) at 52 weeks 3

Impact on Surgery and Systemic Corticosteroid Use

Tezepelumab shows particularly impressive reductions in need for surgery and systemic steroids:

• Tezepelumab reduced the need for nasal polyp surgery to 0.5% compared to 22.1% with placebo (hazard ratio 0.02; 95% CI 0.00 to 0.09) 3
• Systemic glucocorticoid use was significantly lower with tezepelumab (5.2%) versus placebo (18.3%) (hazard ratio 0.12; 95% CI 0.04 to 0.27) 3
• While dupixent trials demonstrated significant improvements across all outcomes, specific surgery avoidance rates were not reported in the same manner in the pivotal trials 5

Safety Profile

Both biologics demonstrate favorable safety profiles:

• All approved biologics, including dupixent, show similar low rates of adverse events leading to discontinuation, with no significant difference from placebo in overall adverse event rates 2
• The most common adverse events with dupixent (nasopharyngitis, worsening nasal polyps and asthma, headache, epistaxis, injection-site erythema) were actually more frequent with placebo 2
• Dupixent may induce conjunctivitis in approximately 2% of patients with CRSwNP, though this was more common in atopic dermatitis trials 2
• Tezepelumab's safety profile in the WAYPOINT trial appears comparable, though long-term safety data are more limited 3

Comorbid Conditions

Dupixent offers advantages for patients with specific comorbidities:

• Dupixent significantly improves asthma outcomes, including FEV1 (MD 0.21; 95% CI 0.20 to 0.22) and asthma control (ACQ scores) in patients with comorbid asthma 2
• Patients with comorbid atopic dermatitis have a dual indication for dupixent, making it the preferred choice in this population 1
• Dupixent benefits are consistent regardless of baseline eosinophil count, presence of comorbid asthma, NSAID-exacerbated respiratory disease, or history of previous nasal polyp surgery 6

Treatment Selection Algorithm

For patients with severe CRSwNP who have failed intranasal corticosteroids for at least 4 weeks:

1. First-line biologic choice: Dupixent for patients with high disease burden (SNOT-22 >40), especially those with comorbid atopic dermatitis 1
2. Alternative first-line: Omalizumab for patients with elevated IgE levels and comorbid allergic asthma 1
3. Consider tezepelumab as an emerging option, particularly for patients who have failed other biologics or when surgery avoidance is a primary concern 3

Critical Implementation Considerations

Common pitfalls to avoid:

• Do not initiate biologics in patients who have not tried intranasal corticosteroids for at least 4 weeks, as this represents the conditional nature of guideline recommendations 1
• Do not assume tezepelumab has equivalent evidence to dupixent, omalizumab, or mepolizumab for CRSwNP given its recent approval and single pivotal trial 1
• Confirm diagnosis of CRSwNP with direct visualization of nasal polyps before initiating any biologic therapy 2
• Consider insurance coverage and cost, as dupixent has broader approval and potentially better formulary access given its earlier market entry 2

Mechanism of Action Context

Understanding the biological targets informs treatment selection:

• Dupixent blocks IL-4 receptor α, inhibiting both IL-4 and IL-13 signaling, which are key drivers of type 2 inflammation involved in IgE synthesis, eosinophil activation, mucus secretion, and airway remodeling 2
• Tezepelumab targets thymic stromal lymphopoietin (TSLP), an upstream epithelial cytokine that initiates type 2 inflammation, potentially offering broader anti-inflammatory effects 3
• The upstream mechanism of tezepelumab may explain its dramatic effects on surgery avoidance, though head-to-head comparative trials are needed 3