Dupixent - Drug Monograph

Introduction

Dupixent (dupilumab) is a groundbreaking biologic medication that represents a significant advancement in the treatment of moderate-to-severe atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. Developed by Regeneron Pharmaceuticals and Sanofi, this human monoclonal antibody received its initial FDA approval in 2017. As the first biologic targeting the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways, Dupixent has transformed the management of these chronic inflammatory conditions that were previously difficult to control with conventional therapies.

Mechanism of Action

Dupixent exerts its therapeutic effects through targeted inhibition of the interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling pathways. The drug specifically binds to the IL-4 receptor alpha subunit (IL-4Rα), which is a shared component of both the Type I receptor (IL-4Rα/γc) and Type II receptor (IL-4Rα/IL-13Rα1). By blocking this critical receptor, dupilumab inhibits IL-4 and IL-13 cytokine-induced inflammatory responses, including:

• Inhibition of Th2-mediated inflammation
• Reduction in IgE production
• Decreased eosinophil recruitment and activation
• Attenuation of inflammatory chemokine production
• Reduction in epithelial barrier dysfunction

This targeted mechanism differs significantly from broad immunosuppressants, offering a more specific approach to controlling type 2 inflammation while preserving broader immune function.

Indications

Dupixent is FDA-approved for: 1. Moderate-to-severe atopic dermatitis in patients aged 6 months and older whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable 2. Moderate-to-severe asthma as an add-on maintenance treatment in patients aged 6 years and older with an eosinophilic phenotype or with oral corticosteroid-dependent asthma 3. Chronic rhinosinusitis with nasal polyposis as an add-on maintenance treatment in adults with inadequate control 4. Eosinophilic esophagitis in patients aged 12 years and older weighing at least 40 kg 5. Prurigo nodularis in adults

Dosage and Administration

• Adults: 600 mg (two 300 mg injections) subcutaneously
• Pediatric patients (12-17 years): Weight-based dosing
• Pediatric patients (6 months to 11 years): Weight-based dosing

• Atopic dermatitis: 300 mg every other week
• Asthma: 200 mg or 300 mg every other week (based on weight and phenotype)
• Chronic rhinosinusitis with nasal polyposis: 300 mg every other week
• Eosinophilic esophagitis: 300 mg weekly

• For subcutaneous injection only
• Pre-filled syringe or pre-filled pen
• Rotate injection sites (thigh, abdomen, or upper arm)
• Allow to reach room temperature for 45 minutes before injection
• Do not inject into tender, bruised, erythematous, or indurated skin

• Renal impairment: No dosage adjustment necessary
• Hepatic impairment: No dosage adjustment necessary
• Elderly: No dosage adjustment necessary
• Pediatric: Weight-based dosing required

Pharmacokinetics

• Bioavailability: ~64%
• Peak concentration: 3-7 days post-dose
• Steady state: Achieved by week 16 with every-other-week dosing

• Volume of distribution: ~4.8 L
• Limited tissue distribution due to large molecular size

• Degraded via proteolytic enzymes throughout the body
• No hepatic cytochrome P450 metabolism

• Half-life: ~3 weeks
• Clearance: Linear at doses ≥300 mg every other week
• No renal or hepatic elimination pathways

Contraindications

1. Hypersensitivity to dupilumab or any component of the formulation 2. Active tuberculosis or other serious infections 3. Patients with known hypersensitivity reactions to rubber or latex (pre-filled syringe components)

Warnings and Precautions

• Anaphylaxis and angioedema have been reported
• Discontinue immediately if severe reaction occurs

• Conjunctivitis and keratitis reported in atopic dermatitis patients
• Regular ophthalmologic examination recommended

• Patients may be at increased risk for parasitic (helminth) infections
• Treat pre-existing infections before initiation

• Avoid live vaccines during treatment
• Consider completing age-appropriate immunizations before initiation

• Transient eosinophilia may occur
• Monitor for clinical manifestations of eosinophilic conditions

Drug Interactions

• Dupilumab may normalize CYP450 enzyme activity by reducing inflammation
• Monitor drugs with narrow therapeutic indices (warfarin, cyclosporine, theophylline)

• Avoid concomitant use with other biologics due to increased infection risk

• Increased risk of infections with concomitant immunosuppressive therapy

• Contraindicated during treatment

Adverse Effects

• Injection site reactions (15-20%)
• Conjunctivitis (8-10%)
• Blepharitis (3-5%)
• Oral herpes (2-4%)
• Keratitis (1-2%)
• Eosinophilia (1-2%)

• Anaphylaxis (<0.1%)
• Angioedema (<0.1%)
• Severe injection site reactions
• Ocular surface disease

• Transient eosinophilia
• Increased creatine phosphokinase

Monitoring Parameters

• Complete blood count with differential
• Hepatic function tests
• Tuberculosis screening
• Parasitic infection screening
• Ophthalmologic examination
• Vaccination status

• Clinical response assessment at 16 weeks
• Ocular symptoms at each visit
• Signs of hypersensitivity reactions
• Infection surveillance
• Eosinophil count (if symptoms develop)

• Atopic dermatitis: EASI score, IGA score, pruritus NRS
• Asthma: Asthma Control Questionnaire, exacerbation rate, FEV1
• Nasal polyposis: Nasal polyp score, SNOT-22 questionnaire
• Eosinophilic esophagitis: Dysphagia symptoms, endoscopic findings

Patient Education

• Proper injection technique training
• Rotation of injection sites
• Recognition of injection site reactions
• Storage requirements (refrigerate at 2-8°C)

• Report eye symptoms promptly (redness, itching, pain, vision changes)
• Recognize signs of allergic reactions (hives, swelling, difficulty breathing)
• Monitor for infections (fever, cough, skin lesions)

• Continue prescribed skin care regimen for atopic dermatitis
• Maintain asthma action plan
• Avoid live vaccines during treatment
• Inform all healthcare providers about Dupixent use

• Do not stop other prescribed medications unless directed
• Keep all scheduled follow-up appointments
• Report pregnancy or planning pregnancy to healthcare provider
• Dispose of needles and syringes properly

References

1. FDA Prescribing Information: Dupixent (dupilumab). 2023 2. Simpson EL, et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med. 2016;375(24):2335-2348 3. Castro M, et al. Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma. N Engl J Med. 2018;378(26):2486-2496 4. Bachert C, et al. Efficacy and Safety of Dupilumab in Patients with Severe Chronic Rhinosinusitis with Nasal Polyps. Lancet. 2019;394(10209):1638-1650 5. Dellon ES, et al. Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. N Engl J Med. 2022;387(25):2317-2330 6. Blauvelt A, et al. Long-term Management of Moderate-to-Severe Atopic Dermatitis with Dupilumab and Concomitant Topical Corticosteroids: LIBERTY AD CHRONOS Study. J Am Acad Dermatol. 2018;78(1):63-71 7. Rabe KF, et al. Safety and efficacy of dupilumab in patients with asthma who require oral corticosteroids. Lancet Respir Med. 2020;8(11):1064-1075 8. Clinical Pharmacology and Biopharmaceutics Review(s). FDA Center for Drug Evaluation and Research