326 Dupilumab: a comparison of infection rates across atopic dermatitis trials in adults, adolescents, children and infants
Authors: Lio Peter , Beck Lisa A , Shi Vivian Y , Chen Zhen  , Khokhar Faisal A , Cyr Sonya L , Gonzalez Tayler 
Published: January 2023

Abstract
Moderate-to-severe atopic dermatitis (AD) is associated with an increased frequency of infections which can lead to hospitalizations. Some treatments used for moderate-to-severe AD can be associated with an increased risk of infection, contributing to a limitation of their long-term use. Dupilumab is a biologic agent that targets the shared signalling pathway for interleukin (IL)-4 and IL-13 and has not been associated with increased risk of overall skin infection rates in clinical trials. To report rates of infection in patients with AD across age groups treated with dupilumab, with a special focus on non-herpetic skin and herpetic infections. We analysed exposure-adjusted infection rates (number of patients per 100 patient-years, nP/100PY) during the study treatment periods for MedDRA terms under the System Organ Class Infections and Infestations (overall infections), including adjudicated skin infections (excluding herpetic infections) and High-Level Term Herpes Virus Infections. Patients with moderate-to-severe AD enrolled in phase 2 (adults) or phase 3 clinical studies received various regimens. Young children (aged 6 months to 5 years, NCT03346434 part B) received dupilumab 200/300 mg (n = 83) every 4 weeks (q4w) or placebo (n = 78) with topical corticosteroids (TCS). Children (aged 6–11 years, NCT03345914) received dupilumab 300 mg q4w (n = 120), or 100/200 mg q2w (n = 122), or placebo (n = 120) with TCS. Adolescents (aged 12–17 years, NCT03054428) received dupilumab 300 q4w (n = 83), or 200/300 mg q2w (n = 82), or placebo (n = 85). Adults (NCT01548404, NCT02210780, NCT01859988, NCT02277743, NCT02277769, NCT02260986 and NCT02755649) received dupilumab 300 mg q2w (n = 746), or 300 mg qw (n = 1095), or placebo (n = 1091). Rates for dupilumab doses are provided in the order specified above. Post-hoc nominal P-values are between dupilumab and placebo. The rate of overall infections (nP/100PY) in the dupilumab treatment groups was numerically lower than in the placebo group in young children (placebo: 246; dupilumab: 185) and in children (placebo: 244; dupilumab: 184, 171) and similar between groups in adolescents (placebo: 204; dupilumab: 210, 181), and in adults (placebo: 129; dupilumab: 134, 126). Adjudicated non-herpetic skin infection rates (nP/100PY) were significantly lower in most dupilumab-treated groups compared with placebo in young children (placebo: 93; dupilumab: 43 [P &lt; 0.05]), children (placebo: 48; dupilumab: 20 [P &lt; 0.05], 28 [n.s.]), and adults (placebo: 27; dupilumab: 16 [P &lt; 0.01], 14 [P &lt; 0.0001]) and numerically lower in adolescents (placebo: 70; dupilumab: 34, 34). Overall herpes infection rates (nP/100PY) in dupilumab treatment groups were similar compared with placebo in young children (placebo: 17; dupilumab: 20), children (placebo: 17; dupilumab: 5, 11), adolescents (placebo: 12; dupilumab: 16, 4) and adults (placebo: 10; dupilumab: 15, 11). Infection rates (nP/100PY) of clinically important herpetic infections, eczema herpeticum and herpes zoster, were numerically lower in dupilumab-treated young children (placebo: 4; dupilumab: 0), adolescents (placebo: 4; dupilumab: 0, 0), and adults (placebo: 4; dupilumab: 2 [n.s.], 1 [P &lt; 0.01]), and numerically higher in children (placebo: 0; dupilumab: 3, 3). Dupilumab treatment in children as young as 6 months of age, and in adolescents and adults with atopic dermatitis is generally associated with lower rates of non-herpetic skin infections compared with placebo and did not increase the risk of overall infections in these data sets.