Dupixent (Dupilumab) for Type 2 Inflammatory Diseases
Overview
Dupixent (dupilumab) is a fully human monoclonal antibody targeting the IL-4 receptor alpha subunit, blocking both IL-4 and IL-13 signaling, and is FDA-approved for multiple type 2 inflammatory conditions including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, prurigo nodularis, and COPD. 1
FDA-Approved Indications & Dosing
Chronic Rhinosinusitis with Nasal Polyps (CRSwNP)
For adults and adolescents ≥12 years with inadequately controlled CRSwNP, administer 300 mg subcutaneously every 2 weeks without a loading dose. 1
- Dupilumab is the only monoclonal antibody approved for CRSwNP and should be used in patients fulfilling criteria for biologic therapy. 2
- The 2023 Joint Task Force guidelines suggest biologics over no biologics (conditional recommendation), with dupilumab and omalizumab showing the most benefit for patient-important outcomes. 2
- Treatment produces clinically meaningful improvements in nasal polyp score (mean difference -1.79), SNOT-22 (mean difference -19.61), sense of smell via UPSIT (mean difference +10.83), nasal congestion (mean difference -0.86), and Lund-Mackay CT scores at 4-6 months. 2
- Benefits are sustained through 52 weeks and occur regardless of comorbid asthma, NSAID-exacerbated respiratory disease, or previous nasal polyp surgery. 3
- Rapid onset: 33.2% of patients regain sense of smell by week 2 versus 5.6% with placebo. 4
Asthma
For adults and adolescents ≥12 years with moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma: 1
- Standard dosing: 400 mg loading dose (two 200 mg injections), then 200 mg every 2 weeks
- For oral corticosteroid-dependent asthma, comorbid moderate-to-severe atopic dermatitis, or comorbid CRSwNP: 600 mg loading dose (two 300 mg injections), then 300 mg every 2 weeks
For children 6-11 years: 1
- 15 to <30 kg: 300 mg every 4 weeks (no loading dose)
- ≥30 kg: 200 mg every 2 weeks (no loading dose)
- If comorbid moderate-to-severe atopic dermatitis, follow atopic dermatitis dosing with loading dose
Limitations: Not for acute bronchospasm or status asthmaticus. 1
Atopic Dermatitis
For adults: 600 mg loading dose (two 300 mg injections), then 300 mg every 2 weeks 1
For children 6 months to 5 years: 1
- 5 to <15 kg: 200 mg every 4 weeks (no loading dose)
- 15 to <30 kg: 300 mg every 4 weeks (no loading dose)
For children 6-17 years: 1
15 to <30 kg: 600 mg loading dose, then 300 mg every 4 weeks
30 to <60 kg: 400 mg loading dose, then 200 mg every 2 weeks
≥60 kg: 600 mg loading dose, then 300 mg every 2 weeks
Can be used with or without topical corticosteroids; reserve topical calcineurin inhibitors for problem areas (face, neck, intertriginous, genital areas). 1
67.8% of patients achieve clinically meaningful benefit by week 2 versus 36.5% with placebo. 4
Eosinophilic Esophagitis
For patients ≥1 year weighing ≥15 kg: 1
- 15 to <30 kg: 200 mg every 2 weeks
- 30 to <40 kg: 300 mg every 2 weeks
- ≥40 kg: 300 mg every week
Prurigo Nodularis
For adults: 600 mg loading dose, then 300 mg every 2 weeks 1
Chronic Obstructive Pulmonary Disease (COPD)
For adults with inadequately controlled COPD and eosinophilic phenotype: 300 mg every 2 weeks (no loading dose) 1
Limitation: Not for acute bronchospasm. 1
Administration
- Subcutaneous injection into thigh, abdomen (except 2 inches around navel), or upper arm (if caregiver administers) 1
- Rotate injection sites with each dose 1
- Allow to reach room temperature before injection: 45 minutes for 300 mg, 30 minutes for 200 mg 1
- Pre-filled pen approved for ages ≥2 years; pre-filled syringe approved for ages ≥6 months 1
- Patients ≥12 years may self-inject under adult supervision (ages 12-17) 1
Pre-Treatment Considerations
Vaccinations
Complete all age-appropriate vaccinations before initiating dupilumab; avoid live vaccines during treatment. 1
Helminth Infections
Treat pre-existing helminth infections before starting dupilumab. If patients develop helminth infection during treatment and don't respond to anti-helminth therapy, discontinue dupilumab until infection resolves. 1
Ocular Assessment
- Patients with significant current or chronic corneal/conjunctival disease should receive routine ophthalmology referral before starting dupilumab. 5
- Delay initiation in patients with history of corneal transplant (until ophthalmology discussion) or reversible acute eye conditions (e.g., infectious conjunctivitis) until resolution. 5
Monitoring Requirements
Laboratory Monitoring
No routine laboratory monitoring (CBC, liver function, renal function, blood pressure, lipids) is required before or during dupilumab treatment. 5
Ocular Surveillance
Conjunctivitis is the most common adverse event, occurring in 6-15% in trials and up to 26.1% in real-world practice. 5
For adults and children ≥7 years with mild-to-moderate symptoms (intermittent foreign body sensation, mild conjunctival injection): 5
- Start preservative-free ocular lubricants
- Refer to ophthalmology if symptoms persist or worsen
- Do not discontinue dupilumab for mild conjunctivitis alone—most cases are self-limited and manageable with artificial tears 5
Emergency referral (<24 hours) required for RAPID symptoms: 5
- Redness (bilateral or unilateral)
- Acuity loss or worsening
- Pain (moderate-to-severe ocular pain, not just irritation)
- Intolerance to light (photophobia)
- Damage to cornea (visible opacity, ulceration, purulent discharge)
For children <7 years: Refer to ophthalmology within 4 weeks for any mild-to-moderate ocular symptoms or mild conjunctival injection/eyelid swelling 5
Prophylactic ocular lubricants are not recommended for patients without pre-existing eye disease. 5
Clinical Response Assessment
For CRSwNP, assess at 16-24 weeks using: 5
- SNOT-22 score
- For comorbid asthma: FEV1 and asthma control questionnaire
Safety Profile
Common Adverse Events
- Most common adverse events (nasopharyngitis, worsening nasal polyps/asthma, headache, epistaxis, injection-site erythema) were more frequent with placebo in CRSwNP trials 2, 3
- Injection site reactions: 7% placebo vs 40% dupilumab 6
- Arthralgias: 5.2% 7
- Rash: 3.2% 7
- Conjunctivitis: 2.8% in real-world respiratory disease cohort 7
Eosinophilia
Dupilumab-associated eosinophilia (≥1.5 × 10³/μL) occurs in 11.3% of patients, with new-onset eosinophilia in 7.7%. 7
- Most cases are transient; 10 of 13 patients with posttreatment eosinophilia had resolution while continuing dupilumab 7
- Eosinophil-related adverse effects are rare 7
- Eosinophilic granulomatous polyangiitis cases are extremely rare (1 patient with eosinophilia, 1 with normal eosinophils on systemic corticosteroids in one cohort) 7
- Treatment benefit persists despite eosinophilia, supporting continued use 7
- Patients with comorbid EGPA may prefer mepolizumab or benralizumab over dupilumab due to potential unmasking of EGPA 2
Hypersensitivity
Hypersensitivity reactions including anaphylaxis, serum sickness, angioedema, urticaria, rash, erythema nodosum, and erythema multiforme have occurred. Discontinue dupilumab if hypersensitivity reaction develops. 1
Arthralgia
Advise patients to report new onset or worsening joint symptoms. If symptoms persist or worsen, consider rheumatological evaluation and/or discontinuation. 1
Corticosteroid Reduction
Do not discontinue systemic, topical, or inhaled corticosteroids abruptly upon dupilumab initiation. Decrease steroids gradually if appropriate. 1
Clinical Decision-Making for CRSwNP
Dupilumab should be considered for patients with CRSwNP who have not sufficiently benefitted from intranasal corticosteroids, surgery, or aspirin therapy after desensitization (ATAD). 2
Prioritize dupilumab in patients with: 2
- High baseline disease severity
- Comorbid atopic dermatitis (dual indication)
- Comorbid asthma requiring biologic therapy
- History of adverse effects from ATAD (GI bleeding, prednisone use, hypertension, diabetes, smoking, male sex, lower BMI)
Consider alternative biologics (mepolizumab, benralizumab) in patients with: 2
- Comorbid EGPA (due to dupilumab's potential to increase peripheral eosinophilia)
Patients with low disease burden who have not tried other therapies might prefer less-invasive intranasal corticosteroids to avoid the burden of systemic therapy and insurance negotiation. 2
Missed Doses
Weekly dosing: Administer as soon as possible, then start new weekly schedule from last dose date 1
Every 2 weeks dosing: 1
- If administered within 7 days of missed dose: resume original schedule
- If >7 days: wait until next scheduled dose
Every 4 weeks dosing: 1
- If administered within 7 days of missed dose: resume original schedule
- If >7 days: administer dose and start new schedule based on this date