P73 Laboratory safety from a 16-week phase III study of dupilumab in patients aged 6 months–5 years with moderate-to-severe atopic dermatitis

Abstract

Abstract Previous studies of dupilumab treatment in adults, adolescents and children aged 6–11 years with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful changes in laboratory parameters. Here, we evaluate laboratory safety data for dupilumab-treated children aged 6 months–5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL (NCT03346434 part B), a placebo-controlled phase III trial, 162 children aged 6 months–5 years with moderate-to-severe AD were randomized to receive dupilumab 200 mg or 300 mg every 4 weeks (n = 83) based on baseline weight (200 mg: ≥ 5 to < 15 kg; 300 mg: ≥ 15 to < 30 kg), or placebo (n = 79) for 16 weeks. Low-potency topical corticosteroids were initiated from day −14. At baseline, mean (SD) haematology parameters were similar in both treatment groups: eosinophils [dupilumab: 1.1 × 109 cells L−1 (0.7); placebo: 1.1 × 109 cells L−1 (0.7)], platelets [dupilumab: 397.7 × 109 cells L−1 (103.2), placebo: 385.6 × 109 cells L−1 (112.9)] and neutrophils [dupilumab: 3.54 × 109 cells L−1 (1.56); placebo: 3.85 × 109 cells L−1 (1.73)]. Mean (SD) counts of neutrophils [dupilumab: 3.18 × 109 cells L−1 (1.94); placebo: 3.79 × 109 cells L−1 (1.91)] remained within the normal reference interval (RI) at week 16. Mean (SD) change in platelet count at week 16 was −16.3 × 109 cells L−1 (78.5) in the dupilumab group and 17.4 × 109 cells L−1 (106.6) in the placebo group. In the dupilumab group, the mean (SD) change in eosinophil count increased at week 4 [0.48 × 109 cells L−1 (1.8)] and trended downward by week 16 [0.31 × 109 cells L−1 (1.4)], while minimal changes were noted in the placebo group at week 4 [0.1 × 109 cells L−1 (0.7)] and week 16 [−0.2 × 109 cells L−1 (0.7)]. The mean (SD) values for creatine kinase [dupilumab: 144.2 U L−1 (84.8); placebo: 130.7 U L−1 (46.39)], alkaline phosphatase [dupilumab: 273.4 U L−1 (80.01); placebo: 233.2 U L−1 (65.98)] and lactate dehydrogenase [dupilumab: 283.8 U L−1 (44.74); placebo: 317.4 U L−1 (67.58)] at week 16 remained within the normal RI in all treatment groups. Two patients treated with dupilumab reported cases of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of study treatment. No clinically meaningful changes in haematology or chemistry laboratory safety parameters in children aged 6 months–5 years with moderate-to-severe AD were seen with 16 weeks of dupilumab treatment. These data demonstrate that, as with adults, adolescents and older children, routine laboratory monitoring is unnecessary in this population. Funding sources: research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.