Overcoming injection issues
The safety profile for dupilumab, which is of the highest importance, “did not surprise me at all,” Dr. Paller said in an interview. “My only surprise is that the placebo injections actually led to more injection site reactions than [with] dupilumab, but numbers were quite low in both groups.” (Rates were 2% among those on dupilumab and 3% among those on placebo.)
The major barrier to the use of dupilumab in clinical practice is the requirement for injection, which, she explained, can be “unbearable for some young children, and thus becomes impossible for parents because of lack of cooperation and their intensified concern about giving the injection,” because of their child’s response.
“We like to administer the first dose in the office, allowing us to teach parents a few tricks related to proper technique,” including audio and visual distraction, tactile stimulation before and during the injection, use of topical anesthetic if helpful, “and making sure that the medication is at room temperature before administration,” she said. Cost is another potential barrier; however, even public insurance has been covering the medication, often after optimized use of topical medications has been unsuccessful.
Future research questions
As for additional research, the current study had a relatively small number of patients younger than 2 years, and more data are needed for this age group, said Dr. Paller. “We also need better understanding of the safety of dupilumab administration when live vaccines are administered. Finally, we certainly want to know what additional effects dupilumab may have beyond just the efficacy for treating eczema.”
In particular, these questions include whether dupilumab modifies the long-term course of the disease, possibly reducing the risk of persistence of disease with advancing age, or even cures the disease if started at a young age, she said. In addition, research has yet to show whether dupilumab might reduce the risk of other atopic disorders, such as asthma, food allergy, and allergic rhinitis.
“Ongoing studies and real-life experiences in the next several years will help us to answer these questions,” Dr. Paller said.
Data support safety, efficacy, quality of life
AD is associated with immense quality of life impairment, Raj Chovatiya, MD, of Northwestern University, Chicago, said in an interview. Most AD is initially diagnosed in early childhood, but previous treatment options for those with moderate to severe disease have been limited by safety concerns, which adds to the burden on infants and young children, and their parents and caregivers, said Dr. Chovatiya, who was not involved in the study.
Dr. Raj Chovatiya
“This phase 3 study showed that dupilumab, a fully human monoclonal antibody that selectively inhibits IL-4 and IL-13 mediated type 2 inflammatory signaling, provided both meaningful and statistically significant improvement in AD severity, extent of disease, and itch in patients,” he said. Dupilumab also improved children’s sleep quality and the overall quality of life in both patients and caregivers.
“These findings were quite similar to those described in older children and adults, where dupilumab is already approved for the treatment of moderate-severe AD and has demonstrated real-world safety and efficacy,” said Dr. Chovatiya. However, “the current study was limited to only a short-term analysis of 16 weeks, an ongoing open-label study should further address long-term treatment responses.”
The study was supported by Sanofi and Regeneron Pharmaceuticals. In addition to being an investigator for Regeneron, and several other pharmaceutical companies, Dr. Paller has been a consultant with honorarium for Regeneron, Sanofi, and multiple other companies. Dr. Chovatiya disclosed serving as a consultant and speaker for Regeneron and Sanofi, but was not involved in the current study.