Dupixent (dupilumab) is a biologic medication approved for treating several inflammatory conditions, including moderate-to-severe atopic dermatitis (eczema), asthma, and chronic rhinosinusitis with nasal polyposis. It works by significantly reducing underlying inflammation. While highly effective, Dupixent is associated with a common ocular side effect known as Dupixent-associated conjunctivitis (DAC). This ocular surface disease is one of the most frequently reported adverse events in patients receiving the therapy. Although the side effect is typically manageable, understanding its cause and treatment is important for patients starting the medication.
Understanding Dupixent’s Role in Immune Modulation
Dupilumab is a monoclonal antibody engineered to target a specific part of the immune system. Its therapeutic action centers on blocking two key signaling molecules, or cytokines: Interleukin-4 (IL-4) and Interleukin-13 (IL-13). These interleukins are considered primary drivers of Type 2 inflammation, which is the underlying immune response in allergic and atopic diseases like eczema and asthma.
The drug works by binding to a component called the IL-4 receptor alpha (IL-4R\(\alpha\)) subunit. This receptor subunit is shared by the signaling pathways of both IL-4 and IL-13, meaning Dupixent acts as a dual inhibitor. By blocking this common receptor, the medication effectively neutralizes the inflammatory signaling cascade, dampening the overall Type 2 immune response.
Recognizing Dupixent-Associated Ocular Symptoms
The ocular side effects associated with Dupixent are collectively referred to as Dupilumab-Associated Ocular Surface Disease (DAOSD), with conjunctivitis being the most common presentation. Clinical trials and real-world data show that the incidence of conjunctivitis can range widely, with the highest rates observed in those treated for atopic dermatitis. Symptoms are often non-specific and can include eye redness, persistent itching (pruritus), and a foreign body sensation.
Patients may also experience excessive tearing, a feeling of dryness, or inflammation of the eyelid, known as blepharitis. More severe, though less common, manifestations include inflammation of the cornea (keratitis), which can lead to light sensitivity and blurred vision. Symptom onset is not immediate, typically appearing a few months after starting treatment. Unlike a typical viral or allergic conjunctivitis that resolves quickly, DAC is often chronic and tends to persist as long as the patient remains on Dupixent.
Proposed Biological Mechanism of Eye Inflammation
The emergence of ocular side effects is a consequence of the immune modulation that makes the drug effective. The current leading hypothesis for DAC is that the blockade of IL-13 disrupts the healthy functioning of the ocular surface. Interleukin-13 plays a crucial role in the proliferation and maintenance of conjunctival goblet cells.
These goblet cells are specialized cells found on the conjunctiva that produce mucin, a slimy substance that forms the innermost layer of the tear film. Mucin is essential for moisturizing the eye surface and ensuring the stability of the tear film, which protects the cornea and conjunctiva. By inhibiting IL-13 signaling, Dupixent can lead to a decrease in goblet cell density and a deficiency in mucin production.
This mucin deficiency results in an unstable tear film that evaporates too quickly, causing dryness and subsequent chronic irritation and inflammation of the ocular surface. Furthermore, blocking the Type 2 pathway may shift the immune balance on the eye toward a different type of inflammation, potentially contributing to the persistent nature of the side effect.
Practical Management of Ocular Side Effects
For most patients, Dupixent-associated conjunctivitis is mild to moderate and can be managed effectively without interrupting their treatment regimen. The initial step in management is frequent, conservative care using preservative-free artificial tears. These lubricants help to supplement the unstable tear film and reduce mechanical irritation and dryness. Applying a warm compress to the eyelids can also help alleviate discomfort and manage any associated blepharitis.
If conservative measures are not sufficient, a healthcare provider can prescribe targeted medical treatments. Short-term use of topical corticosteroid drops is a common intervention to rapidly reduce ocular inflammation and manage acute flare-ups. For more chronic or persistent cases, topical calcineurin inhibitors, such as cyclosporine or tacrolimus, may be used for long-term control. These medications work to modulate the local immune response on the eye surface, often without the side effect profile associated with prolonged steroid use.
Patients should consult an ophthalmologist if symptoms are severe, do not improve with initial treatment, or involve changes to their vision or significant eye pain. While most cases are successfully managed, temporary dose adjustment or, very rarely, discontinuation of Dupixent may be considered if the ocular symptoms are severe or progress despite aggressive management.