Efficacy and Safety of Dupilumab in the Treatment of Atopic Dermatitis in Adolescents

Atopic Dermatitis in Adolescents

The prevalence of AD in the adolescent group worldwide reaches 0.2–24.6% (e.g., 7.0–8.6% in the USA). One third of patients have moderate to severe forms, which negatively affect their quality of life. In adolescents, it is associated with poorer school performance, difficulty in forming relationships, or increased occurrence of anxiety, depression, and suicidal intentions. Topical treatment of AD is mainly effective for mild forms; more severe forms often require systemic therapy.

Dupilumab in AD Therapy

Dupilumab is a fully human monoclonal antibody that blocks the shared receptor subunit for interleukins (IL) 4 and 13. In the USA and European Union, it is an approved medication for subcutaneous administration to patients with severe AD from age 6 and with moderate AD from age 12 who are suitable candidates for systemic therapy.

The results of the clinical study described below, which investigated the efficacy and safety of dupilumab in adolescents with AD inadequately controlled by topical therapy, led to the approval of the drug in this age group.

Study Methodology, Course, and Objectives

The randomized, double-blind, placebo-controlled phase III study with parallel group design was conducted at 45 centers in the USA and Canada between March 2017 and June 2018. It included 251 patients aged 12 to 17 with moderate to severe AD inadequately controlled by topical therapy or in cases where topical treatment could not be prescribed.

Patients were randomized into 3 groups for 16-week treatment with dupilumab or placebo: the 1st group received 200 mg (n = 43; initial body weight < 60 kg) or 300 mg (n = 39; initial weight ≥ 60 kg) every 2 weeks, the 2nd group received 300 mg every 4 weeks (n = 84), and the 3rd group received placebo every 2 weeks (n = 85).

The primary goals were ≥ 75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline and a score of 0 or 1 on the Investigator’s Global Assessment (IGA) scale at week 16 of the study.

Results

A total of 240 patients (95.6%) completed the study. The most common comorbidities among participants were asthma (53.6%), food allergies (60.8%), and allergic rhinitis (65.6%).

The proportion of patients achieving EASI-75 was significantly higher in both treatment groups compared to placebo (1st group 41.5%; 2nd group 38.1%; placebo 8.2%), with the 1st group showing a difference of 33.2% vs. placebo (95% confidence interval [CI] 21.1–45.4%) and the 2nd group showing a difference of 29.9% (95% CI 17.9%–41.8%; p < 0.001 for both comparisons). The proportion of patients with an IGA score of 0 or 1 was also significantly higher in both treatment groups compared to placebo (p < 0.001 for both comparisons). Administering the drug every 2 weeks generally had higher efficacy than every 4 weeks.

Regarding safety assessment, patients treated with dupilumab showed a higher incidence of conjunctivitis (1st group 9.8%; 2nd group 10.8%; placebo 4.7%) and injection site reactions (1st group 8.5%; 2nd group 6.0%; placebo 3.5%), while the incidence of non-herpetic skin infections was lower (1st group 9.8%; 2nd group 9.6%; placebo 18.8%). None of the mentioned adverse events were serious or led to treatment discontinuation.

Conclusion

According to the study results, dupilumab significantly improved AD symptoms and quality of life in adolescents with moderate to severe AD and exhibited an acceptable safety profile. 

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Source: Simpson E. L., Paller A. S., Siegfried E. C. et al. Efficacy and safety of dupilumab in adolescents with uncontrolled moderate to severe atopic dermatitis. JAMA Dermatol 2020 Jan; 156 (1): 44–56, doi: 10.1001/jamadermatol.2019.3336.