What are the indications, dosing, and potential side effects of Dupilumab (dupilumab) for patients with moderate to severe atopic dermatitis, asthma, or chronic rhinosinusitis with nasal polyposis?

Dupilumab: Indications, Dosing, and Side Effects

Primary Indications

Dupilumab is FDA-approved for chronic rhinosinusitis with nasal polyposis (CRSwNP), moderate-to-severe asthma, and atopic dermatitis, with the strongest evidence supporting its use in patients who have failed standard therapies including intranasal corticosteroids and/or surgery. 1

Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP)

• Dupilumab is the only monoclonal antibody approved for CRSwNP and should be used in patients fulfilling criteria for biologic treatment who have inadequate control despite intranasal corticosteroids and/or previous surgery. 2
• The European Rhinology Society recommends dupilumab for patients with severe CRSwNP who remain symptomatic despite standard medical therapy. 2
• The Joint Task Force on Practice Parameters suggests biologics (including dupilumab) over no biologics for CRSwNP, particularly in patients with high baseline disease severity who have not sufficiently benefited from intranasal corticosteroids, surgery, or aspirin therapy after desensitization (ATAD). 2

Asthma

• Dupilumab should be considered for adults and adolescents ≥12 years with uncontrolled moderate-to-severe asthma despite medium-to-high-dose inhaled corticosteroids plus long-acting β2-agonists, optimized adherence and inhaler technique. 3
• Before initiating dupilumab, clinicians must evaluate asthma control status using validated questionnaires and measure FEV1, peak expiratory flow, or perform spirometry. 3

Additional FDA-Approved Indications

• Atopic dermatitis, eosinophilic esophagitis, prurigo nodularis, chronic obstructive pulmonary disease, chronic spontaneous urticaria, and bullous pemphigoid. 1

Mechanism of Action

• Dupilumab is a fully human monoclonal antibody to the IL-4 receptor α subunit, which inhibits signaling of both IL-4 and IL-13. 2
• IL-4 drives T cell differentiation toward the TH2 subtype and induces production of type 2-associated cytokines including IL-5, IL-9, IL-13, TARC, and eotaxin. 3
• Both IL-4 and IL-13 are deeply involved in IgE synthesis, eosinophil activation, mucus secretion, and airways remodeling. 2

Dosing Regimens

For CRSwNP

• Loading dose: 600 mg subcutaneously (two 300 mg injections) 2
• Maintenance: 300 mg subcutaneously every 2 weeks 2, 4
• Administered as add-on therapy to intranasal corticosteroids (mometasone furoate nasal spray 100 μg in each nostril twice daily was used in pivotal trials). 2
• Alternative dosing of 300 mg every 4 weeks after initial 24 weeks showed efficacy in the SINUS-52 trial. 2, 4

For Asthma and Other Indications

• Refer to FDA prescribing information for specific dosing by indication, age, and weight. 1

Clinical Efficacy in CRSwNP

Symptom Improvement

• SNOT-22 score decreased by mean difference of -19.61 points (95% CI -22.53 to -16.69) at 4-6 months, exceeding the minimal clinically important difference of 8.90 points. 2
• Rhinosinusitis disease severity (VAS) decreased by mean difference of -2.54 (95% CI -2.84 to -2.23). 2
• Nasal congestion/obstruction score decreased by mean difference of -0.86 (95% CI -0.98 to -0.75). 2

Objective Measures

• Nasal polyp score decreased by mean difference of -1.79 (95% CI -2.01 to -1.56) in patients with baseline scores around 6, indicating severe polyp disease. 2
• Lund-Mackay CT score decreased by standardized mean difference of -1.50 (95% CI -1.84 to -1.16). 2
• Smell improvement measured by UPSIT score increased by mean difference of 10.83 points (95% CI 9.59 to 12.08). 2

Asthma Outcomes in CRSwNP Patients

• FEV1 improved by mean difference of 0.21 liters (95% CI 0.20 to 0.22) at 4-6 months. 2
• Both ACQ5 and ACQ6 showed significant improvement over placebo in patients with comorbid asthma. 2

Adverse Effects

Common Adverse Events

The most common adverse events (nasopharyngitis, worsening nasal polyps and asthma, headache, epistaxis, injection-site erythema) were paradoxically more frequent with placebo in CRSwNP trials. 2

Conjunctivitis and Ocular Effects

• Dupilumab induces conjunctivitis in trials of patients with atopic dermatitis but NOT in asthma and CRSwNP trials. 2
• Dupilumab-associated ocular surface disease presents as bilateral conjunctival and limbal injection with watery or mucous discharge, typically mild to moderate in severity. 2
• Onset occurs within several weeks to months of initiation, and most cases resolve while continuing treatment. 2
• Patients with mild-to-moderate conjunctivitis should start preservative-free ocular lubricants. 3
• Red flag symptoms requiring emergency ophthalmology referral include redness, acuity loss, pain, intolerance to light, or corneal damage (RAPID acronym). 3
• No routine laboratory monitoring is required, but pre-treatment referral to ophthalmology is recommended for patients with significant corneal/conjunctival disease. 3

Eosinophilia

• Dupilumab-associated eosinophilia (absolute eosinophil count ≥1.5 × 10³/μL) occurred in 11.3% of real-world patients, with 7.7% developing new eosinophilia after treatment initiation. 5
• Most patients with posttreatment eosinophilia (10 of 13) had resolution of eosinophilia while continuing dupilumab. 5
• Eosinophil-related adverse effects are rare, with eosinophilic granulomatous polyangiitis limited to one patient with eosinophilia and one with normal eosinophil levels receiving systemic corticosteroids. 5
• All patients with pretreatment eosinophilia and most with posttreatment eosinophilia received significant treatment benefit, supporting continued use despite eosinophilia. 5

Other Adverse Effects

• Arthralgias: 5.2% (13 of 251 patients) 5
• Rash: 3.2% (8 of 251 patients) 5
• Conjunctivitis: 2.8% (7 of 251 patients) in real-world respiratory indication cohort 5

Clinical Considerations and Monitoring

Patient Selection

• Confirm diagnosis of CRSwNP with endoscopy and/or CT imaging before initiating therapy. 2
• Patients with comorbid conditions and dual indications for dupilumab (e.g., atopic dermatitis and CRSwNP) may particularly benefit. 2
• For patients with eosinophilic granulomatous polyangiitis (EGPA), consider alternative biologics like mepolizumab or benralizumab due to dupilumab's potential to increase peripheral eosinophilia. 2

Monitoring Requirements

• No routine laboratory monitoring is required before or during treatment. 3
• Ocular monitoring is the primary surveillance need, with baseline ophthalmology evaluation for patients with significant corneal/conjunctival disease. 3
• Eosinophil counts may be checked if clinically indicated, but persistent eosinophilia or eosinophil-related adverse effects are rare. 5

Treatment Duration and Discontinuation

• Efficacy demonstrated at 24 weeks with sustained benefit through 52 weeks in pivotal trials. 2, 4
• Most adverse effects are manageable with continued treatment, and resolution often occurs without discontinuation. 2, 5

Contraindications and Precautions

• Hypersensitivity to dupilumab or excipients is a contraindication. 1
• Not for treatment of acute asthma symptoms, acute COPD exacerbations, or acute deteriorating disease. 1
• Systemic corticosteroids should not be abruptly discontinued upon dupilumab initiation; taper gradually if appropriate. 1
• Treat pre-existing helminth infections before initiating therapy; if infection develops during treatment and does not respond to anti-helminth therapy, discontinue dupilumab. 1
• Complete age-appropriate vaccinations before initiating dupilumab. 1