Dupilumab Therapy for Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)

Indications and Patient Selection

Dupilumab is approved only for adults with chronic rhinosinusitis with nasal polyps (CRSwNP); it is not indicated for CRS without polyps. The 2025 American Academy of Otolaryngology guidelines explicitly advise against routine biologic use in CRS without polyps because of insufficient evidence. 1
Ideal candidates are adults who have severe CRSwNP confirmed by bilateral polyps on nasal endoscopy, have failed adequate intranasal corticosteroid therapy, and may have type 2 inflammatory biomarkers (elevated eosinophils, IgE, or FeNO). 1
Patients must demonstrate inadequate response to intranasal corticosteroids despite appropriate use (e.g., mometasone furoate 100 µg per nostril twice daily) before biologic therapy is considered. 2

A minimum of 24 weeks of dupilumab therapy is required to evaluate the full clinical response; optimal outcomes are typically observed at 52 weeks. The phase 3 LIBERTY NP SINUS trials showed continued improvement through 52 weeks. 2
Baseline and follow‑up assessments should include:

Nasal polyp size: Dupilumab produced a mean reduction of ‑1.9 points versus ‑0.3 with placebo (difference ‑1.6; 95 % CI ‑2.4 to ‑0.7). This reflects a clinically meaningful shrinkage of polyps. 2
SNOT‑22: Mean improvement of ‑19.6 points (95 % CI ‑22.5 to ‑16.7), exceeding the minimal clinically important difference of 8.9 points. 2
Nasal congestion: Mean reduction of ‑0.86 points (95 % CI ‑0.98 to ‑0.75). 2
Smell function: Mean UPSIT increase of +10.8 points (95 % CI 9.6 to 12.1), indicating substantial restoration of olfaction. 2

Dupilumab is well tolerated, with no increase in serious adverse events compared with placebo. The most common adverse events (nasopharyngitis, headache, epistaxis) were actually less frequent than with placebo. 2
Conjunctivitis occurs in approximately 2 % of CRSwNP patients receiving dupilumab, a lower rate than observed in atopic dermatitis cohorts. Clinicians should monitor for ocular symptoms. 2

Network meta‑analyses identify dupilumab as the first‑choice biologic for CRSwNP, demonstrating superior efficacy across nasal polyp size, SNOT‑22, nasal congestion, and smell restoration compared with omalizumab and mepolizumab. 3
Alternative biologics:

Do not discontinue intranasal corticosteroids when initiating dupilumab; efficacy data are based on dupilumab added to continued INCS therapy. 2
Avoid assessing treatment failure before 16–24 weeks; early discontinuation leads to suboptimal outcomes because full therapeutic benefit requires this duration. 2
Do not use dupilumab for CRS without nasal polyps; current American Academy of Otolaryngology guidelines recommend against this practice due to lack of supporting evidence. 1
Biologics are not first‑line for all CRSwNP patients; those with low disease burden who have not yet tried INCS or surgery should consider less invasive options before biologic therapy. 3

Dupilumab is indicated for adults with severe CRSwNP refractory to intranasal corticosteroids and prior therapies; patients must meet ≥ 3 of 5 criteria: type 2 inflammation (elevated eosinophils, IgE, or FeNO), prior sinus surgery, need for systemic corticosteroids or ongoing antihistamines, and clinically significant loss of smell 4, 5, 6.

The FDA‑approved regimen is 300 mg subcutaneously every 2 weeks without a loading dose; this is added to continued intranasal corticosteroid therapy (e.g., mometasone furoate 100 µg per nostril twice daily) 7, 6, 8.
The first one to two injections should be given in a clinic or hospital setting for patient training and rare anaphylaxis monitoring; subsequent doses may be self‑administered with an auto‑injector 4.

A minimum of 24 weeks of therapy is required to assess full clinical response, with pivotal phase‑3 trials showing optimal outcomes at 52 weeks 7, 6, 8.
Discontinuation at 24 weeks leads to disease recurrence; therefore, treatment should be continued indefinitely for sustained disease control 7, 6.

Baseline assessments should include: endoscopic nasal polyp score (0–8), Lund‑Mackay CT score (0–24), SNOT‑22 quality‑of‑life score (0–110), UPSIT smell test (0–40), nasal congestion score (0–3), and for comorbid asthma, spirometry (FEV₁), ACQ‑5/6, and exacerbation history 7, 6.
Re‑evaluation is recommended at 16–24 weeks to determine therapeutic response 7, 6.
Monitor for conjunctivitis, which occurs in ≈ 2 % of treated CRSwNP patients, and track systemic corticosteroid use and any need for rescue sinus surgery 9, 7, 6.

At 24 weeks, dupilumab significantly reduces the need for systemic corticosteroids and sinus surgery compared with placebo 7.
In patients with comorbid asthma, dupilumab improves lung function (mean + 0.21 L FEV₁) and asthma control 7, 6, 8.
Benefits are observed regardless of baseline eosinophil count, prior sinus surgery status, or presence of NSAID‑exacerbated respiratory disease 7, 6.

Common adverse events are less frequent than with placebo and include nasopharyngitis 7 and headache 8; epistaxis has been reported in clinical studies 5.
No increase in serious adverse events versus placebo has been demonstrated 7.

Based on network meta‑analyses, dupilumab is the first‑choice biologic for CRSwNP due to superior efficacy across nasal polyp size, SNOT‑22, nasal congestion, and smell restoration 9, 4.
Omalizumab may be preferred for females planning pregnancy 9, 4; mepolizumab is an alternative for patients with highly eosinophilic asthma 9, 4.

Intranasal corticosteroids should be continued as background therapy when initiating dupilumab 7, 6.
Clinicians should allow 16–24 weeks before expecting full therapeutic benefit; early discontinuation may lead to suboptimal outcomes 7.