Dupilumab

Dupilumab is a fully human IgG4 monoclonal antibody that binds with high affinity to the alpha subunit of the interleukin-4 receptor (IL-4Rα). Because IL-4Rα is a shared component of both the type I and type II IL-4 receptor complexes and the IL-13 receptor complex, dupilumab simultaneously inhibits the signalling of two central type-2 inflammatory cytokines — IL-4 and IL-13 — addressing the common upstream pathway of allergic, atopic, and eosinophilic disease.

Mechanism of Action

• Type-2 (Th2) inflammation biology: in atopic, allergic, and eosinophilic conditions, Th2 cells, group 2 innate lymphoid cells (ILC2s), basophils, eosinophils, and mast cells release IL-4, IL-5, IL-9, and IL-13. IL-4 and IL-13 jointly drive Th2 differentiation, IgE class switching, eosinophil and basophil recruitment, mucus hypersecretion, smooth muscle hyperresponsiveness, and the cutaneous barrier defects that underlie atopic dermatitis.
• Receptor structure: IL-4 binds the type I receptor (IL-4Rα + γc) on lymphocytes — driving Th2 differentiation — and the type II receptor (IL-4Rα + IL-13Rα1) on epithelial, smooth muscle, and myeloid cells. IL-13 binds only the type II receptor.
• Dupilumab blockade: by occupying IL-4Rα, dupilumab simultaneously blocks IL-4 signalling through both receptor types and IL-13 signalling through the type II receptor, downregulating the JAK1/STAT6 pathway and suppressing the downstream cascade of cytokines, chemokines (TARC/CCL17, eotaxin-3/CCL26), adhesion molecules, total and allergen-specific IgE, and FeNO.
• Pharmacodynamic biomarkers: rapid reductions in TARC/CCL17, total and allergen-specific IgE, periostin, eotaxin-3, FeNO, and serum LDH; sustained suppression observed across clinical trials. CYP enzymes are not meaningfully altered (an open-label DDI study showed no effect on CYP3A, CYP2C19, CYP2C9, CYP1A2, or CYP2D6 activity).

Pharmacokinetics

• Absorption: subcutaneous bioavailability 61–64% in atopic dermatitis and asthma; Tmax 3–7 days.
• Distribution: estimated volume of distribution 4.8 ± 1.3 L (largely vascular for an IgG).
• Metabolism: catabolised to peptides and amino acids by the reticuloendothelial system; no CYP or transporter pathways.
• Elimination: parallel linear (nonspecific proteolysis) and nonlinear (target-mediated, IL-4Rα saturable) routes.
• Half-life: limited human data — effective dosing half-life supports every-2-week or every-4-week regimens depending on indication.
• Immunogenicity: low rate of treatment-emergent anti-drug antibodies; clinically meaningful neutralising antibodies are uncommon.

Approved indications, with age and regional variation, include:

• Atopic dermatitis — moderate-to-severe in adults and paediatric patients ≥6 months; with or without topical corticosteroids.
• Asthma — add-on maintenance in patients ≥6 years with moderate-to-severe asthma characterised by an eosinophilic phenotype or oral corticosteroid dependence.
• Chronic obstructive pulmonary disease (COPD) — add-on maintenance in adults with inadequately controlled COPD and an eosinophilic phenotype.
• Chronic rhinosinusitis with nasal polyps (CRSwNP) — add-on maintenance in adults inadequately controlled with standard therapy; in EU/Canada used with intranasal corticosteroids.
• Eosinophilic oesophagitis (EoE) — in adults and children ≥1 year weighing ≥15 kg.
• Prurigo nodularis (PN) — moderate-to-severe in adults who are systemic-therapy candidates.
• Chronic spontaneous urticaria (CSU) — in adults and paediatric patients ≥2 years who remain symptomatic despite H1 antihistamine therapy.
• Allergic fungal rhinosinusitis (AFRS) — in adults and paediatric patients ≥6 years with a history of sinonasal surgery.
• Bullous pemphigoid — in adults (approval expanding across regions).

Dupilumab is not indicated for acute bronchospasm or status asthmaticus.

• Hypersensitivity to dupilumab or any of the excipients.

Very common (≥1/10): injection site reactions (erythema, swelling, pain, pruritus), conjunctivitis (notably in atopic dermatitis patients), eosinophilia (usually transient and subclinical).

Common (≥1/100 to <1/10): oral herpes, headache, blepharitis, ocular pruritus, dry eye, keratitis, herpes simplex skin infection, arthralgia.

Uncommon (≥1/1,000 to <1/100): serum sickness or serum-sickness-like reactions, ulcerative keratitis (rare), hypersensitivity reactions including anaphylaxis (very rare), eosinophilic conditions (eosinophilic granulomatosis with polyangiitis — temporal association reported with reduction in oral corticosteroids in asthmatic patients).

Class observation: eosinophil count may transiently rise as the migration cue for tissue infiltration is blocked; persistent or symptomatic eosinophilia warrants evaluation.

• Live vaccines: avoid during dupilumab therapy due to theoretical risk; complete live vaccinations before initiation where possible. Inactivated vaccines remain effective and recommended.
• No clinically meaningful effect on CYP450 enzymes — dupilumab does not require monitoring of CYP substrates.
• Concomitant immunomodulators and biologics: limited interaction data; combination with other immunomodulating biologics is not recommended for the same indication.
• Helminth infections: dupilumab inhibits IL-4/IL-13 signalling, which contributes to the host response against parasitic infections. Treat parasitic infections before initiation; if infection occurs during therapy and does not respond to anti-helminthic treatment, consider stopping dupilumab.

No food or alcohol interactions of clinical significance.

Subcutaneous injection into the thigh, abdomen (except the 5-cm zone around the navel), or upper arm (if administered by a caregiver). Allow the device to reach room temperature for approximately 45 minutes before injection. Rotate injection sites.

Atopic Dermatitis — Adults and Adolescents ≥12 Years and ≥60 kg

• Loading: 600 mg (two 300 mg injections) on day 1.
• Maintenance: 300 mg every 2 weeks.

Atopic Dermatitis — Adolescents 12–17 Years and <60 kg

• Loading: 400 mg on day 1.
• Maintenance: 200 mg every 2 weeks.

Atopic Dermatitis — Children 6–11 Years (Weight-Banded)

• ≥15 to <30 kg: 600 mg loading, then 300 mg every 4 weeks; if inadequate response, may increase to 200 mg every 2 weeks.
• ≥30 to <60 kg: 400 mg loading, then 200 mg every 2 weeks.
• ≥60 kg: same as adult dosing.

Atopic Dermatitis — Children 6 Months to 5 Years (Weight-Banded)

• 5 to <15 kg: 200 mg every 4 weeks (no loading).
• 15 to <30 kg: 300 mg every 4 weeks (no loading).

Asthma (≥12 Years and ≥6 Years per Region) and CRSwNP

• Standard: 400 mg loading on day 1, then 200 mg every 2 weeks; OR 600 mg loading, then 300 mg every 2 weeks for oral-corticosteroid-dependent or comorbid moderate-to-severe atopic dermatitis. Paediatric asthma dosing is weight-banded.

COPD

• Adults: 300 mg every 2 weeks (no loading).

Eosinophilic Oesophagitis (Adults and Paediatric ≥1 Year, ≥15 kg)

• Adults and adolescents ≥40 kg: 300 mg every week.
• Children and adolescents weight-banded: per current labelling.

Prurigo Nodularis (Adults)

• 600 mg loading, then 300 mg every 2 weeks.

Chronic Spontaneous Urticaria

• Adults and adolescents ≥60 kg: 300 mg loading dose, then 300 mg every 2 weeks.
• Paediatric < 60 kg: weight-banded dosing.

Renal/Hepatic Impairment

No dose adjustment.

Missed Dose

For every-2-week dosing: if within 7 days, administer the missed dose then resume the original schedule; if more than 7 days, administer and start a new schedule from the dose date. For every-4-week dosing: administer the missed dose then resume the original schedule.

Conjunctivitis and Keratitis

Conjunctivitis is the most distinctive side effect, particularly in atopic dermatitis patients (where baseline ocular surface disease is common). Counsel patients on lubrication, eyelid hygiene, and prompt evaluation for ulcerative keratitis. Severe or persistent eye disease warrants ophthalmology referral and may require treatment interruption.

Asthma Initiation and Corticosteroid Taper

Do not use dupilumab to treat acute bronchospasm or status asthmaticus. When initiating dupilumab in patients on oral corticosteroids for asthma, taper the corticosteroid gradually — abrupt discontinuation is associated with eosinophilic conditions including eosinophilic granulomatosis with polyangiitis (EGPA). Monitor for vasculitic rash, worsening pulmonary symptoms, cardiac complications, and neuropathy.

Hypersensitivity

Discontinue and treat anaphylaxis or serum-sickness reactions immediately; do not re-challenge after severe reactions.

Cold-Chain Handling

Maintain 2–8 °C; the product can spend up to 14 days at room temperature (≤25 °C) in the original carton if required. Once exposed to temperatures above 25 °C, or kept at room temperature beyond 14 days, discard. Do not freeze; do not shake.

Pregnancy and Lactation

• Pregnancy: limited human data; IgG4 antibodies cross the placenta in the second and third trimesters. Use only if clearly needed.
• Breastfeeding: limited data; benefit-risk assessment required.

Paediatric

Approved from age 6 months for atopic dermatitis; age cut-offs for other indications vary (e.g., ≥1 year for EoE, ≥6 years for asthma in some regions, ≥2 years for CSU).

Elderly

No specific dose adjustment.

Effect on Driving

No influence on the ability to drive or operate machinery.

Store in a refrigerator (2–8°C) in the original carton to protect from light. Do not freeze. If necessary, the pre-filled syringe or pen may be removed from the refrigerator and kept in the pack for up to 14 days at room temperature up to 25°C, protected from light; record the date of removal on the outer carton and discard if left out for more than 14 days or if the expiry date has passed.

3 years from manufacture. Within shelf life, the 14-day room-temperature window applies as a single excursion.

Prescription required (Rx). Cold-chain logistics required for distribution. Often dispensed through specialty pharmacy with patient support programmes for self-injection training.