What are the common and serious side effects of Dupixent (dupilumab) and how should they be managed?

Dupixent (Dupilumab) Side Effects and Management

Most Common Side Effects

Dupixent causes ocular complications in 10-26% of patients with atopic dermatitis, making eye problems the most clinically significant adverse event. 1 These include:

• Conjunctivitis occurs in 6-15% of clinical trial patients and up to 26.1% in real-world studies, presenting as the most frequent ocular complication 1
• Dry eyes affect 13% of all treated patients and 36% of those who develop ocular complications 2
• Keratitis develops in 11% of all patients and 38% of those with ocular surface disorders 2
• Blepharitis occurs in 8% of all patients and 29% of those with eye complications 2
• Injection site reactions are the most common non-ocular adverse event 3, 4
• Upper respiratory tract infections and nasopharyngitis occur frequently 3, 5
• Head and neck dermatitis develops in approximately 19.5% of patients 6

Critical Clinical Context

Eye complications occur specifically in atopic dermatitis patients, NOT in patients using dupilumab for asthma, chronic rhinosinusitis, or eosinophilic esophagitis. 1 This distinction is essential for risk counseling.

Serious Side Effects Requiring Immediate Action

Emergency Ophthalmology Referral (Within 24 Hours)

Use the RAPID acronym to identify patients requiring urgent ophthalmology assessment: 2, 1

Redness of the conjunctiva PLUS any of the following:

• Acuity loss or worsening vision
• Pain (ocular pain, not just irritation)
• Intolerance of light (photophobia)
• Damaged cornea visible or opacity

Unilateral eye symptoms are very unlikely to be dupilumab-related and should be managed through standard ophthalmology pathways. 2, 1

Other Serious Adverse Events

• Allergic reactions including anaphylaxis, severe skin reactions, breathing problems, swelling of face/lips/tongue, or hives require immediate discontinuation and emergency care 3
• Inflammation of blood vessels (vasculitis) rarely occurs, particularly in asthma patients; presents with rash, worsening shortness of breath, persistent fever, chest pain, or numbness 3
• Psoriasis onset can develop in atopic dermatitis patients on dupilumab 3
• Joint aches and pain severe enough to cause walking difficulty or require hospitalization may necessitate drug discontinuation 3

Risk Factors for Ocular Complications

Patients at highest risk for developing dupilumab-related ocular surface disorders (DROSD) include: 1

• Pre-existing dry eye disease with keratitis (OR 6.3,95% CI 1.3-31.6)
• Any prior eye disease (OR 2.97,95% CI 1.76-5.01)
• Prior use of ophthalmic medications (OR 5.16,95% CI 3.11-8.58)
• History of atopic conjunctivitis 7

Management Algorithm for Ocular Complications

Pre-Treatment Assessment

Before starting dupilumab: 2

• Patients with current/chronic corneal or conjunctival disease: Start prophylactic preservative-free ocular lubricants AND refer to ophthalmology via standard pathway 2
• Patients with history of corneal transplant: Delay dupilumab initiation until ophthalmology consultation 2
• Patients with acute reversible eye conditions (e.g., infectious conjunctivitis): Delay dupilumab until resolution 2

During Treatment: Severity-Based Management

For mild DROSD (intermittent symptoms, mild conjunctival injection): 2

• Start preservative-free ocular lubricants 2-4 times daily as first-line treatment 2, 1
• Continue dupilumab without interruption
• Reassess in 2-4 weeks

For moderate DROSD (persistent symptoms not responding to lubricants): 2

• Add topical antihistamine eyedrops (e.g., olopatadine, ketotifen) twice daily to lubricants 2
• Refer to ophthalmology via standard pathway if no improvement 2
• Continue dupilumab

For severe DROSD: 2

• Continue preservative-free lubricants
• Consider tacrolimus 0.1% ointment once daily to lid margins for 4 weeks 2
• Refer to ophthalmology for urgent assessment within 4 weeks 2
• May require short-term topical corticosteroids under ophthalmology supervision

When to Discontinue Dupilumab

Withdraw dupilumab immediately upon ophthalmology confirmation of: 2

• Progressive loss of visual acuity unresponsive to treatment
• Progressive conjunctival cicatrization or scarring
• Requirement for prolonged topical corticosteroid therapy (>8 weeks) with significant risk of ocular adverse effects
• Significant loss of quality of life from inadequately controlled DROSD

Only 4.2% of patients discontinue dupilumab due to ocular complications, indicating most cases are manageable while continuing therapy. 1

Other Notable Adverse Events

• Herpes virus infections including cold sores, herpes simplex virus uveitis, and varicella-zoster virus infections occur more frequently 3, 7
• Hypereosinophilia (elevated eosinophil count) develops in some patients 3
• Alopecia areata has been reported 4
• Arthralgia (joint pain) occurs commonly 3
• Headache, back pain, dizziness, insomnia are frequent non-serious side effects 3

Critical Clinical Pearls

• Ocular complications typically present within weeks to months (usually first 4 months) of starting treatment 1
• Most ocular complications are mild to moderate and manageable with treatment while continuing dupilumab 1
• Bilateral eye involvement is typical for dupilumab-related issues; unilateral symptoms suggest alternative diagnosis 2, 1
• Dupilumab has an excellent overall safety profile with over 10 years of follow-up data 1
• Advise patients to avoid ocular irritants such as smoke, pollution, and cooling fans 2
• If topical corticosteroids are required for >6 weeks, introduce corticosteroid-sparing therapy to avoid complications 8