Advances in the understanding of atopy and atopic disease have paved the way for the use of targeted biologic therapies for children with eczema.
One such therapy, dupilumab, recently received approval from the Food and Drug Administration for the treatment of asthma and atopic dermatitis in children ages 6 and older. Its approval is changing the management of moderate to severe atopic dermatitis and is giving health care providers more tools to make an impact on this frustrating, chronic disease.
Atopic dermatitis is the most common childhood inflammatory skin disorder, with approximately 10% of children affected. It typically presents in infancy with dry skin, eczematous dermatitis and significant pruritus.
Though the pathogenesis is incompletely understood, atopic dermatitis has been found to be primarily a disorder of the skin barrier, immune dysregulation and microbial dysbiosis. It is associated with mutations in the filaggrin gene, which predispose to its development and confer an autosomal dominant inheritance pattern in a subset of patients.
Though the vast majority of children with eczema can be managed with topical therapies, subsets of patients have more severe and/or persistent disease, with significant negative impact on quality of life. In more severely affected patients, adjunctive treatments, including phototherapy and immunosuppressive medications such as methotrexate, cyclosporine and azathioprine, have been only partially effective. In addition, none are FDA-approved for use in children.
Biologic therapies are proving to be an effective alternative.
In the pathogenesis of atopic diseases, there is a shift from T helper 1 (Th1) immune response to T helper 2 (Th2). Th2 cytokines as well as interleukin (IL)-17 and IL-22 contribute to skin barrier dysfunction and the development of atopic dermatitis. Two Th2 cytokines, IL-4 and IL-13, appear to be important drivers of Th2 inflammatory diseases, including asthma, allergic rhinitis and atopic dermatitis (Kim J, et al Allergy Asthma Proc. 2019;40:84-92).
Dupilumab, a fully humanized monoclonal antibody, blocks the shared alpha chain in the receptors for IL-4 and IL-13. In two randomized clinical trials, dupilumab significantly decreased the signs and symptoms of atopic dermatitis, including impact on quality of life, in adolescents and children over age 6 (Kim J, et al. Allergy Asthma Proc. 2019;40:84-92; Simpson EL, et al. JAMA Dermatol. 2020;156:44-56). These findings led to FDA approval for this treatment for children and adolescents in whom traditional topical therapies have failed.
A large randomized controlled trial of children ages 6-11 found dupilumab plus topical corticosteroids improved signs and symptoms of atopic dermatitis in the majority of patients (Paller AS, et al. J Am Acad Dermatol. 2020;83:1282-1293). Up to 70% of treated patients achieved Eczema Area Severity Index-75 (an objective measurement of improvement in atopic dermatitis) vs. 26% in the placebo group. Reported side effects were minimal and included injection site reactions, nasopharyngitis and conjunctivitis.
With supportive care, dupilumab treatment often can be continued in patients experiencing these side effects. Dupilumab requires no routine laboratory monitoring and is considered immunomodulatory rather than immunosuppressive, which is a major benefit for the targeted age range.
Studies of dupilumab in children ages 6 months to 6 years with atopic dermatitis are ongoing. Given the success of the medication in school-age children and adolescents, it is hopeful it will be available for use in younger children in the coming year.
Unravelling the mystery of atopic diseases has been a key scientific achievement of the past decade. The inclusion of children in clinical trials for these and other inflammatory disorders also is a large step forward. It is essential to develop therapeutics that are used on-label in childhood, improving both the safety and outcomes for our youngest patients.
Drs. Maguiness and Tollefson are members of the AAP Section on Dermatology.