564 - Conjunctivitis adverse events in dupilumab clinical trials

Abstract

Abstract Introduction Dupilumab inhibits signaling of IL-4 and IL-13, key drivers of Type 2 inflammatory diseases such as atopic dermatitis (AD), asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), eosinophilic esophagitis (EoE), prurigo nodularis (PN), and Chronic Spontaneous Urticaria (CSU).1,2 Adults with AD have a significant and disease severity-dependent increased risk of developing ocular surface diseases, including conjunctivitis and keratitis, compared with the general population.3 In randomized placebo-controlled trials of dupilumab in patients with moderate-to-severe AD, more conjunctivitis events were reported in patients who received dupilumab treatment than in placebo-treated patients.4,5 Objective This analysis reviewed the incidence, severity, and resolution of conjunctivitis adverse events (AEs) in patients from clinical trials evaluating dupilumab in AD, asthma, CRSwNP, EoE, PN, and CSU. Methods “Conjunctivitis” refers to the group of MedDRA Preferred Terms (PTs) that include the term ‘conjunctivitis’, namely conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, adenoviral conjunctivitis, and atopic keratoconjunctivitis. All cases of conjunctivitis were included regardless of etiology (including blepharoconjunctivitis, which was coded as the MedDRA PT conjunctivitis, and excluding blepharitis in the absence of conjunctivitis. This analysis excludes events of keratitis. Randomized, double-blinded, placebo-controlled trials included in this analysis were: Liberty AD Solo 1, Liberty AD Solo 2, Liberty AD Chronos, LIBERTY AD ADOL, LIBERTY AD PEDS, LIBERTY AD PRESCHOOL Part B (AD); Liberty Asthma Quest, Liberty Asthma Venture (asthma); Liberty NP Sinus-24, Liberty NP Sinus-52 (CRSwNP); Liberty EoE Treet (EoE); Liberty PN Prime, Liberty-PN Prime2 (PN); and Liberty-CSU Cupid Part A (CSU). Results Overall conjunctivitis incidence was higher in patients receiving dupilumab vs placebo in all randomized AD trials, with 7.9% to 19.4% of adult dupilumab-treated patients and 4.8% to 14.8% of dupilumab-treated patients aged 6 months to <18 years experiencing conjunctivitis events. In contrast, conjunctivitis rates were <5% and similar between dupilumab and placebo in the asthma, CRSwNP, EoE, PN, and CSU trials. Most conjunctivitis cases observed in adult patients with AD receiving dupilumab treatment were mild to moderate in severity, with severe conjunctivitis being reported at rates of ≤0.6%. A majority of all conjunctivitis cases in dupilumab-treated adults with AD were resolved during the treatment period. Conclusions Overall conjunctivitis events were more frequent in dupilumab-treated vs placebo-receiving patients in AD trials across ages, whereas rates were low and similar between dupilumab and placebo groups in the asthma, CRSwNP, EoE, PN, and CSU trials. Most conjunctivitis cases observed in adult patients with AD receiving dupilumab treatment were mild to moderate in severity and resolved by the end of the study period. Current evidence suggests that conjunctivitis associated with dupilumab occurs predominantly in patients with AD. It is possible that pre-existing ocular disorders and a dupilumab–AD disease-specific interaction may be responsible for this increased incidence in dupilumab-treated patients with AD.