Past, Present, and Future of Pediatric Atopic Dermatitis Management

Newer topical nonsteroidal agents may offer several opportunities. First, they may help avoid local and systemic adverse effects that often limit the use of current standard therapy.⁸ This capability may prove essential in bridging TC treatments and serving as long-term maintenance therapies to decrease the frequency of eczema flares. Second, they can alleviate the need for different medication strengths for different body regions, thereby allowing for simplification of regimens and potentially increased adherence and decreased disease burden—a boon to affected patients and caregivers.

Although the efficacy and long-term safety profile of these new drugs require further study, it does not seem unreasonable to look forward to achieving levels of optimization and individualization with topical regimens for AD in the near future that makes flares in patients with mild to moderate AD a phenomenon of the past.

Advances in Systemic Therapy

Systemic therapeutics in pediatric AD also recently entered an exciting era of development. Traditional systemic agents, including cyclosporine, methotrexate, azathioprine, and mycophenolate mofetil, have existed for decades but have not been widely utilized for moderate to severe AD in the United States, especially in the pediatric population, likely because these drugs lacked FDA approval and they can cause a range of adverse effects, including notable immunosuppression.⁹

Introduction and approval of dupilumab in 2017 by the FDA was revolutionary in this field. As a monoclonal antibody targeted against IL-4 and IL-13, dupilumab has consistently demonstrated strong long-term efficacy for pediatric AD and has an acceptable safety profile in children and adolescents.^10-14 Expansion of the label to include children as young as 6 months with moderate to severe AD seems an important milestone in pediatric AD care.

Since the approval of dupilumab for adolescents and children aged 6 to 12 years, global experience has supported expanded use of systemic agents for patients who have an inadequate response to TCs and previously approved nonsteroidal topical agents. How expansive the use of systemics will be in younger children depends on how their long-term use impacts the disease course, whether therapy is disease modifying, and whether early use can curb the development of comorbidities.

Investigations into targeted systemic therapeutics for eczematous dermatitis are not limited to dupilumab. In a study of adolescents as young as 12 years, tralokinumab (an IL-13 pathway inhibitor) demonstrated an Eczema Area Severity Index-75 of 27.8% to 28.6% and a mean decrease in the SCORing Atopic Dermatitis index of 27.5 to 29.1, with minimal adverse effects.¹⁵ Lebrikizumab, another biologic IL-13 inhibitor with strong published safety and efficacy data in adults, has completed short- and longer-term studies in adolescents (NCT04178967 and NCT04146363).¹⁶ The drug received FDA Fast Track designation for moderate to severe AD in patients 12 years and older after showing positive data.¹⁷

This push to targeted therapy stretches beyond monoclonal antibodies. In the last few years, oral JAK inhibitors have emerged as a new class of systemic therapy for eczematous dermatitis. Upadacitinib, a JAK1 selective inhibitor, was approved by the FDA in 2022 for patients 12 years and older with AD and has data that supports its efficacy in adolescents and adults.¹⁸ Other JAK inhibitors including the selective JAK1 inhibitor abrocitinib and the combined JAK1/2 inhibitor baricitinib are being studied for pediatric AD (NCT04564755, NCT03422822, and NCT03952559), with most evidence to date supporting their safety and efficacy, at least over the short-term.¹⁹