Dupilumab - Drug Monograph

Introduction

Dupilumab is a fully human monoclonal antibody that represents a breakthrough in the treatment of type 2 inflammatory diseases. As the first biologic therapy targeting the interleukin-4 (IL-4) receptor alpha subunit, it inhibits signaling of both IL-4 and IL-13, key drivers of type 2 inflammation. Approved by the FDA in 2017, dupilumab has transformed the management of several chronic inflammatory conditions that were previously difficult to control with conventional therapies.

Mechanism of Action

Dupilumab binds specifically to the IL-4 receptor alpha subunit, which is a shared component of both the type I (IL-4) and type II (IL-4 and IL-13) receptor complexes. By inhibiting IL-4 and IL-13 signaling, dupilumab reduces the inflammatory cascade associated with type 2 immunity. This includes decreased production of inflammatory cytokines, chemokines, and immunoglobulin E (IgE), reduced eosinophil migration and activation, and improved barrier function in affected tissues. The drug does not bind to or neutralize cytokines directly but rather blocks the receptor site they would typically occupy.

Indications

Dupilumab is FDA-approved for:

• Moderate-to-severe atopic dermatitis in patients aged 6 months and older whose disease is not adequately controlled with topical prescription therapies
• Moderate-to-severe asthma in patients aged 6 years and older with an eosinophilic phenotype or oral corticosteroid-dependent asthma
• Chronic rhinosinusitis with nasal polyposis in adults whose disease is not adequately controlled
• Eosinophilic esophagitis in patients aged 12 years and older weighing at least 40 kg

Dosage and Administration

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

• Pediatric patients: Dosing based on weight (≥5 kg to <15 kg: 200 mg loading dose, then 200 mg every 4 weeks; ≥15 kg to <30 kg: 300 mg loading dose, then 200 mg every other week; ≥30 kg: 400 mg or 600 mg loading dose, then 200 mg or 300 mg every other week)
• Hepatic impairment: No dosage adjustment required
• Renal impairment: No dosage adjustment required
• Elderly: No dosage adjustment required

Pharmacokinetics

Contraindications

• Known hypersensitivity to dupilumab or any of its excipients
• Active tuberculosis or other serious infections (relative contraindication requiring careful risk-benefit assessment)

Warnings and Precautions

Drug Interactions

• Live vaccines: Avoid concurrent administration
• Cytochrome P450 substrates: Dupilumab may normalize CYP450 enzyme activity in patients with high levels of inflammation, potentially affecting metabolism of concomitant drugs (particularly warfarin, cyclosporine, and certain anticonvulsants)
• Systemic corticosteroids: Dupilumab may allow for corticosteroid dose reduction; taper slowly under medical supervision

Adverse Effects

• Injection site reactions (erythema, pain, swelling)
• Conjunctivitis
• Blepharitis
• Oral herpes
• Keratitis
• Eosinophilia
• Headache

• Anaphylaxis/angioedema
• Helminth infections
• Severe ocular surface disease
• Serum sickness-like reactions

Monitoring Parameters

• Complete blood count with differential
• IgE levels (if available)
• Ophthalmic examination in patients with pre-existing ocular conditions
• Screening for parasitic infections in endemic areas
• Tuberculosis screening

• Clinical response assessment at regular intervals
• Ocular symptoms at each visit
• Eosinophil count (particularly in asthma patients)
• Signs of hypersensitivity reactions
• Monitoring for helminth infections in endemic areas
• Assessment of concomitant corticosteroid reduction

• Annual ophthalmic examination in patients with persistent ocular symptoms
• Continued monitoring of clinical efficacy and safety

Patient Education

• Instruct on proper subcutaneous injection technique using pre-filled syringe or pen
• Rotate injection sites (thigh, abdomen, or upper arm)
• Recognize and report signs of hypersensitivity (rash, itching, swelling, dizziness)
• Report new or worsening eye symptoms (redness, itching, pain, vision changes)
• Inform healthcare providers about dupilumab use before receiving vaccinations
• Do not stop concomitant medications unless advised by healthcare provider
• Seek immediate medical attention for symptoms of severe allergic reaction
• Store medication in refrigerator (36°F-46°F); may be kept at room temperature up to 14 days
• Dispose of used needles and syringes in puncture-proof container

References

1. Beck LA, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371(2):130-139. 2. Wenzel S, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma. N Engl J Med. 2018;378(26):2486-2496. 3. Bachert C, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps. Lancet. 2019;394(10209):1638-1650. 4. Dellon ES, et al. Dupilumab in adults and adolescents with eosinophilic esophagitis. N Engl J Med. 2022;387(25):2317-2330. 5. Dupixent® (dupilumab) prescribing information. Regeneron Pharmaceuticals Inc. and Sanofi-Aventis U.S. LLC; 2023. 6. Blauvelt A, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287-2303. 7. Castro M, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med. 2018;378(26):2475-2485.