P4A042: Dupilumab Treatment of Children with Moderate-to-severe Atopic Dermatitis Increases Bone Alkaline Phosphatase, a Marker of Bone Mineralization

Background: Children with atopic dermatitis (AD) are at risk for low bone mineral density (BMD) which is associated with low bone alkaline phosphatase (BALP). A determinant for lifetime risk of fractures and osteoporosis is the magnitude of peak bone mass achieved during prepubescent years. Low BALP and BMD in children with moderate-to-severe AD could contribute to a higher prevalence of osteopenia and osteoporosis in patients with AD.

Objective: To report the impact of dupilumab (DPL) treatment on markers of bone formation in children aged ≥6 to < 12 years with moderate-to-severe AD.

Methods: The analysis was performed retrospectively on sera from participants in LIBERTY AD PEDS (NCT03345914) and LIBERTY AD PED-OLE (NCT02612454). In LIBERTY AD PEDS, a double-blind, 16-week, phase 3 trial, children aged 6 to < 12 years were randomized 1:1:1 to 300mg DPL every 4 weeks (300mg q4w), a weight-based regimen of DPL every 2 weeks (baseline [BL] weight < 30 kg: 100mg q2w; BL weight ≥30 kg: 200mg q2w), or placebo (PBO); with concomitant medium-potency topical corticosteroids (TCS). After the initial 16-week trial, children aged 6 to < 12 years were enrolled in the open-label extension study LIBERTY AD PED-OLE. Patients (pts) received DPL 300mg q4w, which could be titrated up in case of inadequate clinical response at Week 16 (BL weight < 60 kg: 200mg q2w; BL weight ≥60kg: 300mg q2w); with concomitant medium-potency TCS. Bone biomarkers including BALP, procollagen type 1 N-terminal propeptide, C-terminal crosslinking telopeptide of type 1 collagen, osteocalcin, and insulin-like growth factor 1 were analyzed at BL, week 8, 12, 16 and BALP only at 52 weeks.

Results: DPL treatment led to a rapid and significant increase in geometric mean (standard error) levels of BALP at 16 weeks vs PBO group (77.7(1.02)μg/L vs 65.0(1.04)μg/L; P< 0.0001), as well as a rapid and significant increase in BALP levels in children from the PBO group once they joined the OLE trial. BALP levels increased over 52 weeks in all treated children, reaching a level of 78–84μg/L which constitutes a significant improvement compared with BL and reference intervals. With treatment, an increasing trend from BL to 16 weeks was observed for other biomarkers, but there was a limited number of data points due to insufficient volumes of serum for analysis.

Conclusion: These PBO-controlled results show a rapid and significant increase in BALP, and a possible trend in other biomarkers, in children with AD during treatment with DPL. These results suggest increased bone mineralization during the treatment period.