What are the differences in outcomes for chronic rhinosinusitis and nasal polyps treatment between approved biological agents, including Tezspire (tezepelumab) and dupilumab?

Comparative Outcomes of Biologics for Chronic Rhinosinusitis with Nasal Polyps

Dupilumab and omalizumab demonstrate the most beneficial outcomes for chronic rhinosinusitis with nasal polyps (CRSwNP) across patient-important measures, with dupilumab showing particularly superior effects on disease-specific quality of life (SNOT-22 improvement of -19.91 points) and nasal symptoms compared to other biologics including mepolizumab, while tezepelumab lacks specific approval or robust evidence for CRSwNP treatment. 1

FDA-Approved Biologics for CRSwNP

The currently approved biologics for CRSwNP treatment include:

• Dupilumab (anti-IL-4Rα): 300 mg subcutaneously every 2 weeks 1
• Omalizumab (anti-IgE): Dosing varies by weight and IgE levels 1
• Mepolizumab (anti-IL-5): Standard dosing for CRSwNP 1

Tezepelumab (anti-TSLP) is mentioned in surgical guidelines as a potential option but lacks the robust evidence base and specific FDA approval for CRSwNP that the other three agents possess. 1

Comparative Efficacy on Disease-Specific Quality of Life

SNOT-22 Outcomes (MID = 8.9 points)

Dupilumab achieves the largest improvement in SNOT-22 scores with a mean difference of -19.91 points (95% CI: -22.50, -17.32), exceeding the minimally important difference by more than twofold. 1

• Omalizumab produces a mean difference of -16.09 points (95% CI: -19.88, -12.30) 1
• Mepolizumab shows more modest improvements compared to dupilumab and omalizumab 1
• Real-world evidence confirms these findings, with dupilumab demonstrating particularly notable effects across multiple follow-up timepoints 2

Nasal Symptom Score Improvements (MID = 1 point on 0-10 scale)

All three primary biologics exceed the minimally important difference for nasal symptoms, with dupilumab again leading:

• Dupilumab: -3.25 points (95% CI: -4.31, -2.18) 1
• Omalizumab: -2.09 points (95% CI: -3.15, -1.03) 1
• Mepolizumab: -1.82 points (95% CI: -3.13, -0.50) 1

Objective Measures

Nasal Polyp Score Reduction

Dupilumab consistently demonstrates superior nasal polyp reduction across both randomized controlled trials and real-world studies. 1, 2, 3

• At 24 and 52 weeks, dupilumab significantly reduced nasal polyp scores compared to placebo 1
• Real-world data shows nasal polyp scores decreasing from baseline of 5-6 to 0-1 after 12 months of dupilumab treatment 4
• All biologics show significant polyp reduction, but indirect comparisons favor dupilumab 5

Sinus Opacification (Lund-Mackay Score)

Dupilumab produces significant improvements in CT scan opacification scores at both 24 and 52 weeks, with benefits maintained in long-term real-world studies. 1, 3

Olfactory Function (UPSIT)

Dupilumab demonstrates significant improvement in smell identification testing, with benefits observed as early as 16 weeks and sustained through 52 weeks. 1, 3

Safety Profile Comparison

All approved biologics demonstrate similar low rates of adverse events leading to discontinuation, with no significant difference from placebo in overall adverse event rates, though certainty of evidence is low to very low. 1

Agent-Specific Safety Considerations

• Omalizumab: Anaphylaxis risk of 0.09% in asthma populations 1
• Dupilumab: Conjunctivitis in 2% of CRSwNP patients 1; generally well-tolerated in real-world settings with high treatment adherence over 4 years 6
• Mepolizumab: Low discontinuation rates due to adverse events in real-world studies 2

Clinical Context for Biologic Selection

When Dupilumab is Preferred

Patients with high baseline disease burden who have failed intranasal corticosteroids for at least 4 weeks should preferentially receive dupilumab or omalizumab based on superior efficacy across multiple patient-important outcomes. 1

• Comorbid atopic dermatitis provides dual indication for dupilumab 1
• Comorbid asthma with type 2 inflammation benefits from dupilumab regardless of baseline eosinophil count 3
• Previous biologic exposure does not diminish dupilumab efficacy 4

When Omalizumab is Preferred

Patients with elevated IgE levels and comorbid allergic asthma represent the ideal population for omalizumab. 1

• Second-best efficacy profile after dupilumab across patient-important outcomes 1
• Established safety profile with rare but serious anaphylaxis risk requiring monitoring 1

When Mepolizumab is Preferred

Patients with eosinophilic granulomatosis with polyangiitis (EGPA) should receive mepolizumab or benralizumab rather than dupilumab, which may increase peripheral eosinophilia and potentially unmask EGPA. 1

• May reduce need for revision surgery 7
• Appropriate for patients with high eosinophil counts and comorbid severe eosinophilic asthma 1

Aspirin-Exacerbated Respiratory Disease (AERD)

In AERD patients, biologics are preferred over aspirin therapy after desensitization (ATAD) for those with increased bleeding risk (history of GI bleeding, prednisone use, hypertension, diabetes, smoking, male sex, lower BMI). 1

• All three primary biologics show efficacy in AERD populations 1
• Combining biologics with ATAD may provide additive benefit, though evidence is limited 7

Tezepelumab's Limited Role

Tezepelumab is mentioned only in the 2025 surgical guidelines as a potential option for limited polyposis but lacks the evidence base, FDA approval specificity, and guideline support that dupilumab, omalizumab, and mepolizumab possess for CRSwNP. 1

• No inclusion in the 2023 Joint Task Force network meta-analysis comparing biologics 1
• No dedicated efficacy data for CRSwNP outcomes in the provided evidence
• Should not be considered equivalent to the three established biologics for CRSwNP treatment

Predictors of Response and Recurrence

Baseline eosinophil levels, IgE, and FeNO may predict superior response to specific biologics, though robust predictive tools remain a critical unmet need. 7

• Prior endoscopic sinus surgery may predict better biologic outcomes, though evidence is limited 7
• Dupilumab likely demonstrates the lowest recurrence rates after cessation given its superior efficacy during active treatment 7, 8
• Comorbid asthma may predict better response since biologics dosed for asthma provide continuous treatment 8

Treatment Sequencing Algorithm

For patients with CRSwNP who have used intranasal corticosteroids for at least 4 weeks without adequate symptom control:

1. High disease burden + comorbid atopic dermatitis → Dupilumab first-line 1
2. High disease burden + elevated IgE + allergic asthma → Omalizumab first-line 1
3. High disease burden + EGPA or concern for EGPA → Mepolizumab or benralizumab, avoid dupilumab 1
4. AERD with bleeding risk factors → Any biologic preferred over ATAD 1
5. Severe obstruction or neo-osteogenesis → Consider surgery before or concurrent with biologics 1

Real-World Performance

Real-world studies demonstrate that biologic efficacy for CRSwNP exceeds that observed in phase 3 randomized controlled trials, with sustained benefits over 4 years and high patient satisfaction. 2, 6

• Revision surgery and oral steroid use become rare during biologic therapy 6
• Some patients successfully extend injection intervals or discontinue intranasal corticosteroids 6
• Biologic switching for inadequate response or side effects is infrequent but generally well-tolerated 6

Common Pitfalls

Avoid initiating biologics in patients who have not tried intranasal corticosteroids for at least 4 weeks, as this represents the conditional nature of the guideline recommendation. 1

• Do not assume tezepelumab has equivalent evidence to dupilumab, omalizumab, or mepolizumab for CRSwNP 1
• Do not overlook dual indications (asthma, atopic dermatitis) that may guide biologic selection 1
• Do not use dupilumab in patients with known or suspected EGPA without careful consideration 1
• Do not delay surgery in patients with severe obstruction, neo-osteogenesis, or fungal disease, as these may require surgical intervention for biologics to be effective 1