at 31 treatment centers in North America and Europe.
Children younger than 6 years with moderate to severe AD have few options if their symptoms are uncontrolled with topical therapies, and persistent itchiness has a negative impact on quality of life for patients and families, Amy S. Paller, MD, professor and chair of dermatology, and professor of pediatrics at Northwestern University, Chicago, and colleagues wrote in the study, published in the Lancet.
Dr. Amy S. Paller
The study was the basis of the Food and Drug Administration expanded approval of dupilumab in June 2022, to include children aged 6 months to 5 years with moderate to severe AD, whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Regulatory submission for this age group is under review by the European Medicines Agency, and by regulatory authorities in other countries, according to the manufacturers.
Dupilumab (Dupixent), which inhibits the signaling of the interleukin-4 and IL-13 pathways, was first approved in 2017 for treating adults with moderate to severe AD.
“There has not been a biologic approved before at such a young age, and for such a common disease,” Dr. Paller said in an interview. “This is the drug that has revolutionized care of the most common inflammatory skin disease in children, and this is the pivotal study that brought it to market for the youngest children who suffer from the severe forms.”
The study also sets a precedent for a lower threshold for starting systemic medication in young children for treating moderate to severe disease given the absence of severe side effects and no need for lab monitoring, Dr. Paller noted. However, dupilumab will also be closely watched “for both impact on the developing immune system and the possibility that it will alter the long-term course of the eczema and the development of allergic comorbidities, such as lowering the risk of developing asthma, GI, allergy, and possibly other conditions.”
In the study, the researchers randomized 83 children aged 6 months up to 6 years to treatment with dupilumab, administered subcutaneously, and 79 to placebo every 4 weeks for 16 weeks; both groups also received topical corticosteroids. Dosage of dupilumab was based on body weight; those with a body weight of 5-15 kg received 200 mg, while those with a body weight of 15-30 kg received 300 mg. The primary endpoint was the proportion of patients with clear or almost clear skin at 16 weeks, defined as scores of 0 or 1 on the Investigator’s Global Assessment.
After 16 weeks, 28% of dupilumab patients met the primary endpoint versus 4% of those on placebo (P < .0001). In addition, 53% of dupilumab patients met the key secondary endpoint of a 75% improvement from baseline in Eczema Area and Severity Index, compared with 11% of patients on placebo (P < .0001). Treatment with dupilumab also resulted in significantly greater improvements in pruritus and skin pain, and sleep quality, as well as improved quality of life for patients and their caregivers, the authors reported.
Overall, adverse event rates were slightly lower in the dupilumab-treated patients, compared with patients on placebo (64% vs. 74%); there were no adverse events related to dupilumab that were serious or resulted in treatment discontinuation. Treatment-emergent adverse effects that were reported in 3% or more of patients and affected more of those on dupilumab than those on placebo included molluscum contagiosum (5% vs. 3%), viral gastroenteritis (4% vs. 0), rhinorrhea (5% vs. 1%), dental caries (5% vs. 0), and conjunctivitis (4% vs 0).
The rate of skin infections among the children on dupilumab was 12% vs. 24% among those on placebo.
Severe and treatment-related adverse events also were similar in both subgroups of body weight.
The findings were limited by the small number of patients younger than 2 years and the lack of study sites outside of North America and Europe, the researchers noted. However, the results were strengthened by the randomized, double-blind design and use of background topical therapy to provide a real-world safety and efficacy assessment in a very young population.