P93 Dupilumab treatment in children with moderate-to-severe atopic dermatitis increases levels of bone mineralization biomarkers

Abstract Children with atopic dermatitis (AD) are at risk for lower bone mineral density (BMD) and lower alkaline phosphatase (ALP) levels than healthy children. Low BMD and ALP in children could contribute to a higher lifetime prevalence of fractures, osteopenia and osteoporosis. Dupilumab is a fully humanized monoclonal anti-interleukin (IL)-4R antibody approved for the treatment of AD in children. The objective of this analysis is to report the impact of dupilumab treatment on markers of bone mineralization in children aged 6–12 years with moderate-to-severe AD vs. reference intervals (RIs). Analysis was performed retrospectively on sera from participants in LIBERTY AD PEDS, a phase III placebo-controlled trial of 16 weeks (NCT03345914) and LIBERTY AD PED-OLE (NCT02612454), an open-label extension trial in which eligible patients received dupilumab until week 52. Biomarkers, including bone ALP (BALP), procollagen type 1 N-terminal propeptide (P1NP), C-terminal crosslinking telopeptide of β-1 collagen (β-CTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1), were analysed at baseline, 8, 12 and 16 weeks; only BALP was measured at 52 weeks. Both dupilumab dosing regimens led to significant increases in geometric mean (SE) levels of BALP at 8, 12 and 16 weeks compared with placebo. For the 100/200-mg Q2W group, at week 8 the BALP level was 72.7 (1.03) μg L−1 vs. 62.0 (1.05) μg L−1 (P < 0.0001), at week 12 it was 74.7 (1.03) μg L−1 vs. 64.3 (1.05) μg L−1 (P < 0.001) and at week 16 it was 78.0 (1.03) μg L−1 vs. 65.0 (1.04) μg L−1 (P < 0.001). For the 300-mg Q4W group, at week 8 the BALP level was 76.7 (1.03) μg L−1 vs. 62.0 (1.05) μg L−1 (P < 0.001), at week 12 it was 73.3 (1.04) μg L−1 vs. 64.3 (1.05) μg L−1 (P = 0.002) and at week 16 it was 77.3 (1.03) μg L−1 vs. 65.0 (1.04) μg L−1 (P < 0.001). At 52 weeks, BALP levels were statistically significantly increased compared with baseline [placebo vs. placebo transitioned to dupilumab: 64.2 (1.04) μg L−1 vs. 82.9 (1.04) μg L−1 (P < 0.001); 100/200 mg Q2W: 62.0 (1.05) μg L−1 vs. 83.8 (1.03) μg L−1 (P < 0.001); 300 mg Q4W: 64.1 (1.04) μg L−1 vs. 78.7 (1.04) μg L−1 (P < 0.001)] and also increased within RIs. From baseline to week 16, OC, P1NP and β-CTX levels improved from below to within the RIs, and levels of IGF-1 increased from the lower limit of the RI. However, data points were limited due to insufficient sera volumes, preventing statistical analyses for these biomarkers. The overall results suggest an increase in bone mineralization biomarkers in paediatric patients with moderate-to-severe AD following dupilumab treatment. Funding sources:research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.