AMSTERDAM — , revealed a post hoc trial analysis.
The research was presented at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.
The trial included a “rigorously selected … well-characterized, well-studied” population of children aged 6-11 years, said presenter Alan D. Irvine, MD, DSc, professor of dermatology, Trinity College Dublin, Ireland.
It showed that “severe atopic dermatitis does cause restriction of growth, as well as a higher weight, and therefore obviously a higher BMI [body mass index].”
He continued, however, that children at the lower percentiles of height receiving prompt treatment with dupilumab (Dupixent) “were able to rapidly move through the centiles over the 16 weeks of the study, and that may be the window for catch-up growth … when children are growing rapidly.”
Anna Yasmine Kirkorian, MD, chief of dermatology, Children’s National Hospital, Washington, DC, who was not involved in the study, said that she was “surprised” at the degree of growth achieved over the study period, as height is not something that jumps up “overnight.”
“On the other hand, it fits with my experience with children who’ve had the brakes on all of their life due to inflammation, whether it be height, going to school, sleeping — everything is sort of put on pause by this terrible inflammatory process,” she said.
“When you take the brakes off, they get to be who they are going to be,” Kirkorian added. “So I was surprised by the speed of it, but not by the fact that height was acquired.”
Her belief is that in the pre-dupilumab era, severe atopic dermatitis was often insufficiently controlled, so children were “smaller than you would predict from parental height,” and the treatment is “allowing them to reach their genetic potential.”
Post Hoc Analysis
In his presentation, Irvine emphasized that it has been clearly demonstrated that adolescents with moderate and severe atopic dermatitis have a significantly higher likelihood of being below the 25th percentile of height on growth reference charts.
Such children are also at a higher risk of having low bone mineral density and low serum alkaline phosphatase (ALP) levels . While data presented at the EADV 2023 Congress showed that dupilumab significantly increased serum levels of bone ALP compared with placebo, the underlying mechanism remains unclear.
For the current analysis, Irvine and colleagues determined that the proportion of children aged 6-11 years with severe atopic dermatitis and lower stature reach a ≥ 5 centile improvement in height following 16 weeks of dupilumab treatment.
They examined data from the LIBERTY AD PEDS trial, in which patients aged 6-11 years with severe atopic dermatitis were randomized to 300 mg dupilumab every 4 weeks or placebo along with a mild or moderately potent topical corticosteroid. The study found that, overall, dupilumab was associated with significant improvements in signs, symptoms, and quality of life compared with placebo.
Height measures at baseline revealed that “more boys and more girls were below the 50th centile than you would predict for a healthy, normal control population,” Irvine said. “If we look at weight, we see the opposite,” he continued, “with a disproportionate number of boys and girls who are above the 50th centile for weight at baseline.”
Consequently, “we’re seeing these children who are shorter and heavier than the predicted healthy weight range and, as a result, obviously have higher BMI,” Irvine noted, with 67% girls and 62% boys found to have a higher BMI than normal for their age.
After 16 weeks of treatment with dupilumab, there was a much greater gain in height than that seen among those on placebo, with the most pronounced effect seen in children who had the lowest height at baseline. Indeed, among children in the lowest 25% height percentile at baseline, 30.6% on dupilumab vs 11.9% on placebo experienced an increase in height of 5 centiles or more(P < .05).
“This reflects what we see in clinical practice,” Irvine said. “Children often grow dramatically on treatment for atopic dermatitis.”
Among patients with a baseline height below the 30th percentile, 31.9% treated with dupilumab vs 11.1% treated with placebo gained at least 5 centiles in height. The figures for children below the 40th height percentile at baseline were 31.3% vs 15.5% (P < .05 for both).
Although there remained a marked difference in the proportion of children below the 50th height percentile at baseline gaining 5 centiles or more in height, at 29.0% with dupilumab versus 15.7% with placebo, it was no longer significant.
“So the effect of catch-up growth, or growth through the centiles, is most marked in those who are in the 40th centile or below,” Irvine said, indicating that the “more growth restricted kids have much more potential to catch up.”