What are the potential side effects associated with the use of Dupixent (dupilumab)?

Side Effects Associated with Dupixent (Dupilumab)

The most significant side effect of Dupixent is dupilumab-related ocular surface disorders (DROSD), occurring in 32-55% of patients with atopic dermatitis, manifesting as conjunctivitis, dry eye, keratitis, and blepharitis. 1

Primary Ocular Side Effects

Incidence and Presentation

• Conjunctivitis occurs in 6-26% of patients in clinical trials and real-world studies, presenting with bilateral conjunctival and limbal injection, watery or mucous discharge, and follicular or papillary changes 2
• Dry eye disease affects 13% of all treated patients and 36% of those who develop ocular complications 2
• Keratitis is observed in 11% of all patients and 38% of those with ocular issues 2
• Blepharitis affects 8% of all patients and 29% of those with ocular complications 2

Geographic Variation in Incidence

Real-world data shows significant geographic variation in DROSD rates: UK (32-42%), France (13.3-18%), Italy (11-12.2%), USA (8.1%), and South Korea (5%) 1

Critical Risk Factors for DROSD

Pre-existing Ocular Disease

• History of any eye disease increases risk substantially (OR 2.97,95% CI 1.76-5.01) 1
• Prior use of ophthalmic medication is the strongest predictor (OR 5.16,95% CI 3.11-8.58) 1
• Pre-existing dry eye disease with keratitis significantly elevates risk (OR 6.3, CI 1.3-31.6) 1
• Eyelid eczema is a major risk factor (OR 8.7, CI 1.8-40.6) 1

Important Clinical Distinction

• DROSD is specific to atopic dermatitis patients - systematic reviews show comparable rates of ocular surface disease in placebo versus dupilumab-treated patients with asthma, chronic rhinosinusitis, and eosinophilic esophagitis 1
• This AD-specific risk is confirmed by real-world US prescription database analysis 1

Other Systemic Side Effects

Common Non-Ocular Adverse Events

• Injection site reactions are among the most common side effects 3
• Upper respiratory tract infections occur frequently 3
• Herpes virus infections, including cold sores and potentially more severe manifestations 3, 4
• Elevated eosinophil counts (eosinophilia) 3
• Nasopharyngitis (common cold symptoms) 3

Less Common but Important Side Effects

• Joint aches and pain can occur, with some patients experiencing trouble walking or requiring hospitalization 3
• Psoriasis can develop in patients with atopic dermatitis and asthma 3
• Inflammation of blood vessels (vasculitis) rarely occurs, particularly in asthma patients 3

Serious Allergic Reactions

Emergency Signs Requiring Immediate Discontinuation

The FDA label specifies stopping Dupixent immediately if any of these occur 3:

• Breathing problems or wheezing
• Swelling of face, lips, mouth, tongue, or throat
• Hives or severe skin rash (including bullseye pattern, painful red/blue bumps, or red pus-filled spots)
• Fainting, dizziness, or feeling lightheaded
• Fast pulse with fever and general ill feeling

Management Algorithm for Ocular Complications

Red Flag Symptoms Requiring Emergency Referral (< 24 hours)

Seek emergency ophthalmology evaluation immediately if conjunctival redness occurs with ANY of the following 2, 5:

• Decreased visual acuity
• Ocular pain
• Photophobia (light sensitivity)
• Visible corneal damage

First-Line Management

• Initiate preservative-free ocular lubricants 2-4 times daily at the first sign of any ocular symptoms 2, 5
• Most ocular complications are mild-to-moderate and manageable while continuing dupilumab 2
• Only 4.2% of patients discontinue dupilumab due to ocular complications 2, 5

Prophylactic Approach

• Consider prophylactic preservative-free lubricants in high-risk patients, though evidence is mixed - some Italian studies showed DROSD rates as low as 1.9-7.2% with prophylaxis, while a London study showed 76% despite prophylaxis 1

Critical Clinical Pearls

Distinguishing Dupilumab-Related from Other Causes

• Bilateral involvement is typical for dupilumab-related ocular issues 2, 5
• Unilateral eye symptoms are very unlikely to be dupilumab-related and should prompt evaluation for other causes through standard ophthalmology pathways 2, 5

Timing and Natural History

• Most ocular complications present within weeks to months of starting treatment, typically within the first 4 months 2
• Interestingly, DROSD was not associated with a history of allergic conjunctivitis 1

Overall Safety Profile

Despite the high incidence of ocular side effects, dupilumab has an excellent overall safety profile with over 10 years of follow-up data 2, and the vast majority of patients can continue treatment with appropriate ocular management.