Conjunctivitis in dupilumab clinical trials

BACKGROUND: Dupilumab, which blocks the shared receptor component for interleukin (IL)-4 and IL-13, is approved for inadequately-controlled moderate-to-severe atopic dermatitis (AD) and moderate-to-severe eosinophilic or oral corticosteroid-dependent asthma. AD trials reported increased conjunctivitis incidence for dupilumab vs. placebo. OBJECTIVES: To further characterise conjunctivitis occurrence and risk factors in dupilumab clinical trials. Methods We evaluated randomised placebo-controlled trials of dupilumab in AD (n=2629), asthma (n=2876), chronic rhinosinusitis with nasal polyps (CRSwNP) (n=60), and eosinophilic esophagitis (EoE) (n=47). RESULTS: In most AD trials, dupilumab-treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous conjunctivitis history were associated with increased conjunctivitis incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered/resolved during the treatment period; 2 patients permanently discontinued dupilumab due to conjunctivitis/keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and anti-histamines/mast cell stabilisers. Most cases were diagnosed by investigators. In asthma and CRSwNP trials, conjunctivitis incidence was lower for both dupilumab and placebo than in AD trials; dupilumab did not increase incidence vs. placebo. In the EoE trial, no patients had conjunctivitis. CONCLUSIONS: Conjunctivitis was more frequent with dupilumab treatment in most AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, conjunctivitis incidence was associated with AD severity and prior history of conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab-treated patients require further study.