Systemic treatment in infants
The Liberty AD PRESCHOOL phase 3 trial that supported the FDA’s approval of dupilumab down to 6 months of age, published in 2022 in The Lancet, covered ages 6 months to 5 years but included only six children under the age of 2, “leaving us with a very limited dataset in this age group,” Dr. Eichenfield said at the meeting.
University of California, San Diego
Dr. Lawrence F. Eichenfield
Other data and analyses that have provided reassurance, such as a laboratory safety analysis published online in 2022 showing no meaningful changes in laboratory safety parameters in children as young as 6 months, and pediatric data (not including infants) presented at a RAD meeting in 2022 showing that dupilumab, an interleukin-4 receptor alpha antagonist, may have positive effects on bone mineral density.
Data from the Liberty AD PRESCHOOL open-label extension study presented at the American Academy of Dermatology meeting in 2023, meanwhile, show that “the adverse event profile is not looking much different than what we see in older children,” Dr. Eichenfield said. “There are low rates of severe adverse events and a very low rate of discontinuations.”
At Rady Children’s Hospital, where Dr. Eichenfield is chief of pediatric and adolescent dermatology, dupilumab has become a first-line systemic agent for severe infantile AD, supplanting prior traditional but little used systemic agents such as oral corticosteroids, cyclosporine, methotrexate, azathioprine, or mycophenolate, he said after the meeting.
The decision to use systemics in the first 2 years of life is “a comprehensive one,” requiring knowledge of the child’s history, disease course, and assessment of response to prior therapies, comorbidities and severity, he said.
Food allergy in infants with AD
Food allergy is common in children with moderate to severe AD, but true food-triggered AD, with AD being the only symptom of food allergy, is rare, said Anne Marie Singh, MD, associate professor in the division of allergy and immunology and rheumatology at the University of Wisconsin, Madison, who focuses on pediatrics.
Over the years, studies of double-blind placebo-controlled food challenge tests in children with AD have tended to conflate immediate IgE hypersensitivity (and skin symptoms like urticaria) with AD, said Dr. Singh, who directs the university’s Food Allergy Research and Education Center of Excellence. In a recently published study she led involving 374 children with AD referred to allergy and/or dermatology subspecialty clinics at the University of Wisconsin, Madison, 55% had a food allergy but only 2% had food-triggered AD “where eczema is the only symptom and removal of the food cleared up the eczema and its return brought it back,” Dr. Singh said at the meeting. Another 4% had combined IgE-mediated food allergy and food-triggered AD. Almost half of the children with food-triggered AD were under 1 year of age, and egg was the most common trigger, she noted.
Food should be implicated largely by history, Dr. Singh emphasized.
Food allergy testing in the context of AD can be done but is challenging, with the clinical relevance of skin prick testing and food-specific immunoglobulin E (sIgE) difficult to predict. Predictive values of sIgE levels are established for immediate IgE mediated food allergy, but “cut-offs” for food-triggered AD are not established, she explained, noting that “cut-offs are likely higher for our children with AD.”
Elimination diets, moreover, pose significant risks of future oral tolerance and risks of nutritional deficiencies and poor growth, Dr. Singh said. New and immediate reactions to foods that are reintroduced after an elimination diet are common, and research has shown that 20% or more of such reactions involve anaphylaxis. “If an elimination diet is undertaken, you need emergency action plans, injectable epinephrine, and nutrition counseling,” she said.
A recent systematic review and meta-analysis conditionally recommended against elimination diets for the treatment of AD, Dr. Singh noted.
Asked by Dr. Sidbury whether there “is a sweet spot where you can eliminate [foods] without going all the way,” Dr. Singh said she will sometimes do a “diagnostic elimination trial” with food elimination for 2-4 weeks only – a time period after which “I’ll feel really comfortable reintroducing the food.”
Dr. Singh urged dermatologists to “know your allergist” because “patients respond best with a consistent message.”
Dr. Sidbury reported ties with Regeneron, UCB, Pfizer, Leo Pharma, Lilly, and Beiersdorf. Dr. Siegfried reported ties with Pfizer, Regeneron, Sanofi Genzyme, Pfizer, UCB, Novan and Leo Pharma. Dr. Singh reported ties with Incyte and Siolta Therapeutics. Dr. Eichenfield reported ties with Pfizer, Regeneron, Sanofi Genzyme, Incyte, and Pfizer.