Generic Name

Dupilumab

Mechanism

• IL‑4/IL‑13 blockade – Dupilumab binds IL‑4Rα, preventing receptor dimerization with the common γ‑chain (for IL‑4) or IL‑13Rα1 (for IL‑13).
• Suppression of downstream signaling – Inhibition of STAT6 activation reduces transcription of genes driving IgE class switching, mucus hypersecretion, and epidermal‑filament keratinocyte activation.
• Reversal of type‑2 inflammation – Decreases eosinophil recruitment, reduces Th2 cytokine milieu, and restores barrier functions in skin and airway epithelia.

Pharmacokinetics

• Absorption: Rapidly absorbed after subcutaneous injection; peak serum concentration (Cmax) achieved within 1‑2 days.
• Bioavailability: ~80 % after SC dosing.
• Half‑life: ~16 days (steady‑state ~20‑22 days).
• Distribution: Low volume of distribution (~8 L) with distribution largely confined to the vascular and interstitial spaces.
• Metabolism & Elimination: Predominantly catabolized via proteolytic pathways; minimal renal elimination.
• Dose‐dependent clearance: Mildly lower in patients with higher baseline body weight; the standard 300 mg regimen maintains target exposure across weight ranges.

Indications

• Moderate‑to‑Severe Atopic Dermatitis – Adults, adolescents 12 yr+, and children 6 yr+ (loading dose 300 mg SC, then 300 mg q2wk).
• Moderate‑to‑Severe Asthma – Adults and adolescents 12 yr+ uncontrolled by inhaled corticosteroids plus long‑acting β‑agonists; 200 mg SC q2wk.
• Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) – Adults and adolescents 12 yr+; 300 mg SC q2wk.
• Prurigo Nodularis – Investigational; pediatric use pending regulatory approval.

Contraindications

• Hypersensitivity – IgE‑mediated allergy to any component of the formulation (PEG, polysorbate 80).
• Active opportunistic infections – Avoid in patients with severe, uncontrolled infections or those requiring systemic immunosuppressants.
• Pregnancy/Lactation – No definitive safety data; use only if benefits outweigh risks.
• Uncontrolled atopy or eosinophilic disorders – Monitor for worsening eosinophilia.

Dosing

• Administration – Subcutaneous injection (70 mg/ml in prefilled syringe or autoinjector).
• Premedication – Not routinely required; antihistamine may be used if history of mild allergic reaction.
• Adjuncts – Continue baseline therapy (e.g., inhaled corticosteroids) unless clinically indicated for tapering.

Adverse Effects

• Common (≥10 % incidence)
• Injection‑site reaction (erythema, pruritus, induration)
• Conjunctivitis/blepharoconjunctivitis
• Nasopharyngitis
• Periorbital dermatitis
• Upper‑respiratory‑tract infection
• Serious (≤1 %)
• Severe eosinophilic reactions (organ‑related)
• Otitis media with effusion (especially in children)
• Serious systemic infections (e.g., tuberculosis, fungal)
• Anaphylaxis (rare; < 0.1 %)
• Optic neuritis (isolated case reports)

Monitoring

• Baseline and periodic CBC with differential – to detect eosinophilia.
• Ophthalmologic exam – at baseline and every 3–6 months (or sooner if symptoms).
• Efficacy assessment – EASI (atopic dermatitis), ACT (asthma), SNOT‑22 (CRSwNP).
• Liver function tests – not routinely required but consider if concomitant hepatotoxic drugs.
• Immunization status – live vaccines contraindicated while on therapy.

Clinical Pearls

• Injection technique – Rotate sites (abdomen, thigh, upper arm) to avoid lipoatrophy and injection‑site reactions.
• Dose adjustment for weight – Children  500 cells/µL may necessitate dose suspension and evaluation for hypereosinophilic syndrome.
• Pregnancy counseling – Limited human data; decision should involve shared decision‑making with patient and obstetrics team.

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• *Prepared for medical students and healthcare professionals seeking a concise, evidence‑based reference on Dupilumab.*