John Jesitus is a medical writer based in Westminster, CO.
In a recent phase 3 trial, dupilumab (Dupixent, Sanofi and Regeneron) demonstrated positive results in itch reduction, skin clearance and quality-of-life. Indicating the biologic as a viable treatment option for severe atopic dermatitis in younger children.
The efficacy and safety of dupilumab (Dupixent, Sanofi and Regeneron) in children ages 6 to 11 years with severe atopic dermatitis (AD) provides an acceptable option for a previously underserved population, says the principal investigator on the phase 3 LIBERTY AD PEDS trial.
“We finally have dupilumab for an age group where it’s so critical, and there hasn’t been anything other than immunosuppressants to treat these children,” says Amy S. Paller, M.D, chair and professor in the Department of Dermatology, and professor of pediatrics (dermatology) at Northwestern University Feinberg School of Medicine.
Between ages six and 11, she says, children are starting school and forming early social relationships, which are difficult if children are tormented by AD and associated itching and disturbances of sleep and concentration. “Ages 6 to 11 is their time to venture out into the real world and a very critical time for their psychosocial development.”
In the study, investigators randomized 362 patients to dupilumab every two weeks (100 mg if weight <30 kg, 200 mg if ≥ 30 kg), dupilumab every four weeks (300 mg regardless of weight) or placebo. All patients also used topical corticosteroids (TCS).
At week 16, significantly more patients on dupilumab every two weeks (29.5%) or four weeks (32.8%) achieved the primary endpoint of investigator global assessment (IGA) score of 0 (clear) or 1 (almost clear) versus placebo (11.4%). Eczema Area and Severity Index (EASI) 75 scores were 67.2%, 69.7% and 26.8%, respectively. Whereas twice-monthly dosing proved most effective in all prior dupilumab AD trials, pharmacokinetic values and clinical impact were greater with the 300 mg every four-week dose versus 100 mg every two weeks in children weighing less than 30 kg.
“Dupilumab did not just affect the objective signs of atopic dermatitis,” Dr. Paller adds, “but incredibly importantly, it also brought down the itch as early as in the first two weeks and profoundly affected quality of life for these young children.”
As in previous dupilumab trials in AD, injection-site reactions and conjunctivitis (mostly mild to moderate) were the only treatment-emergent adverse events (TEAEs) that occurred more frequently with dupilumab than with placebo. The fact that fewer TEAEs overall occurred with dupilumab may stem from dupilumab’s ameliorative effects on comorbid type 2 inflammatory conditions and on skin (fewer skin infections), write Paller et al.
Dupilumab is highly effective in adolescent asthma, says Dr. Paller, and it is being studied for other type 2 comorbidities. “For example, it’s looking very good for eosinophilic esophagitis. It’s also being studied for severe allergic rhinitis and food allergies. So, we know that it has the promise to be effective across a range of Th2-driven disorders.” Such capability would be welcome, she says, because more than 90% of adolescents with moderate AD, and younger children with severe AD, have at least one other type 2 disorder.
“That means that we may be able to treat more than one of their diseases with a single agent.” The asthma or other comorbidities are usually less severe than the AD, Dr. Paller says. But the possibility of stopping other medications used for some of these comorbidities is appealing for families and children, she adds.
Dupilumab’s success against AD in children ages 6 to 11 years is already a breakthrough, says Dr. Paller. “For kids who have never been able to get the control I wanted because I was unwilling to put them on a systemic medication, now I’ll be able to give them something that’s acceptable to parents, that’s not going to require labs every month, and that’s even going to give them better control than a medication like cyclosporine.”
1. Paller AS, Siegfried EC, Thaçi D, et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial [published online ahead of print June 20, 2020]. J Am Acad Dermatol. 2020;S0190-9622(20)31152-X. doi:10.1016/j.jaad.2020.06.054.
Dr. Paller has been an investigator and consultant for AbbVie, Castle Creek, Eli Lilly, Galderma, Lenus, LEO, Novartis and Regeneron; an investigator for Incyte, Janssen and Verrica; and a consultant for Almirall, Amgen, Asana, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Exicure, Forte BioPharma, MEDACorp, Meiji Seika, Novan, Pfizer, Sanofi Genzyme, Sol-Gel and UCB.