Dupilumab in Children Aged 6 Months to Younger Than 6 Years With Uncontrolled Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial

To assess the efficacy and safety of dupilumab with concomitant topical corticosteroids as a treatment option for moderate-to-severe atopic dermatitis (AD) in children aged 6 months to younger than 6 years.

The study included 162 participants from 31 hospitals, clinics, and academic institutions in North America and Europe. Eligible participants were diagnosed with moderate-to-severe AD according to consensus criteria of the American Academy of Dermatology with Investigator’s Global Assessment (IGA) scores of 3 or 4 and were deemed as having an inadequate response to topical corticosteroids (defined as a course of topical corticosteroids for 28 days within the past 6 months).

This was a randomized, double-blind, placebo-controlled, parallel-group, phase 3 trial among 31 hospitals, clinics, and academic institutions in Europe and North America. Eighty three participants were randomly assigned to dupilumab plus low-potency topical corticosteroids and 79 were randomly assigned to placebo plus low-potency topical corticosteroids. Participants were treated with subcutaneous placebo or dupilumab (200 mg for weight ≥ 5 kg to 15 kg or 300 mg for baseline weight of ≥15 kg to <30 kg) every 4 weeks plus low potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. The primary endpoint was the proportion of participants with clear or almost clear skin (IGA score of 0 or 1). The key secondary endpoint was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index. There were additional secondary endpoints that included weekly mean of daily worst scratch and itch Numerical Rating Scale, change from baseline in proportion of body surface affected, and change from baseline in patient’s sleep quality Numerical Rating Scale score. The study also measured safety outcomes while taking dupilumab.

Dupilumab was significantly more effective than placebo in improving the primary and secondary endpoints. Forty one percent of patients in the dupilumab group achieved an IGA of 0 or 1 compared with 11% in the placebo group. Additionally, 69% of participants in the dupilumab group achieved Eczema Area and Severity Index-75 compared with 23% in the placebo group. Other outcomes also had statistically significant improvements in sleep quality and quality of life. The study also found that dupilumab was generally well-tolerated, with a safety profile consistent with previous studies in older patients. Participants in the dupilumab group had a lower incidence of skin infections and AD exacerbations compared with the placebo group.

This study shows that children aged 6 months to 6 years old with moderate to severe AD can safely use dupilumab in adjunct with low-potency topical corticosteroids. It also showed that the combination of dupilumab and low-potency topical corticosteroids significantly improved AD signs, symptoms, and quality of life compared with placebo.

Per the American Academy of Dermatology, 25% of children are affected by AD with an estimated 60% developing the condition within the first year of life. AD significantly affects quality of life of affected children and their families and topical steroids alone do not provide adequate relief for many of those with moderate to severe disease. Not only is it encouraging to have another effective therapy for our most affected patients, but because dupilumab dampens Th2 inflammation, it may have the potential to provide additional benefits long-term once therapy is discontinued secondary to interference with the establishment of an atopic phenotype early in immunologic development. Additional studies will be necessary to understand the full potential for use of dupilumab early in life in atopic children.