338 Laboratory safety from a 16-week phase 3 study of dupilumab in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis

Abstract

Abstract Many systemic therapies used for moderate-to-severe atopic dermatitis (AD) have immunosuppressive properties and necessitate laboratory screening and monitoring, adding to the treatment burden. Previous dupilumab studies in adults, adolescents and children aged 6–11 years with moderate-to-severe AD showed no clinically meaningful adverse changes in laboratory parameters. Here we evaluate hematology and chemistry laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (NCT03346434 part B), a randomized, double-blind placebo-controlled phase 3 study. 162 patients were randomized to either dupilumab 200/300 mg every 4 weeks (q4w; N = 83; baseline weight ≥5 <15 kg: 200 mg; ≥15 to <30 kg: 300 mg) or placebo (N = 79) for 16 weeks. From Day –14, all patients initiated standardized treatment with low-potency topical corticosteroids. Laboratory data was collected at baseline, weeks 4 and 16. At baseline, mean (SD) counts of hematology parameters were similar in both treatment groups: haemoglobin (dupilumab: 129.4 gL−1 [12]; placebo: 127.2 gL−1 [11.4]), lymphocyte (dupilumab: 4.6 × 109 L−1 [1.8]; placebo: 4.5 × 109 L−1 [1.7]), basophil (dupilumab: 0.07 × 109 L−1 [0.03]; placebo: 0.07 × 109 L−1 [0.04]), platelet (dupilumab: 397.7 × 109 L−1 [103.2]; placebo: 385.6 × 109 L−1 [112.9]) and eosinophils (dupilumab: 1.1 × 109 L−1 [0.7]; placebo: 1.1 × 109 L−1 [0.7]). Mean (SD) haemoglobin count in the dupilumab (128.4 × gL−1 [11]) and placebo groups (128.2 × gL−1 [11.2]), lymphocyte count in the dupilumab (4.20 × 109 L−1 [2.06]) and placebo groups (4.29 × 109 L−1 [1.52]) and basophil count in the dupilumab (0.07 × 109 L−1 [0.04]) and placebo groups (0.06 × 109 L−1 [0.03]) remained with the normal reference range for this population at week 16. The mean change (SD) in platelet count at week 16 was −16.3 × 109 L−1 (78.5) in the dupilumab group and +17.4 × 109 L−1 (106.6) in the placebo group. In the dupilumab treatment group, the mean eosinophil count increased at week 4 (mean change from baseline [SD]; + 0.48 × 109 L−1 [1.8]) and trended downward by week 16 (+0.31 × 109 L−1 [1.4]) while minimal changes were noted in the placebo group at week 4 (0.1 × 109 L−1 [0.7]) and week 16 (−0.2 × 109 L−1 [0.7]). The values for creatine kinase, alkaline phosphatase, lactate dehydrogenase, blood urea nitrogen, albumin and protein at week 16 remained within the normal reference range in all treatment groups. Two patients in the dupilumab 200/300 mg q4w arm of this study reported treatment-emergent adverse events of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of the study treatment. No clinically meaningful changes in hematology and chemistry parameters in children aged 6 months to 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 younger population. Dupilumab was generally well tolerated with an acceptable safety profile.