After 16 weeks of treatment, the primary endpoint ― an Investigators Global Assessment (IGA) score of 0 or 1 with at least a 2-point improvement from baseline ― was met by 41.7% of patients given 2 mg (those younger than age 10) or 4 mg of baricitinib (those aged 10 to 17 years), the highest dose studied in each of those two age groups.
By comparison, the primary endpoint was met in 16.4% of children in the placebo group (P < .001).
Baricitinib is approved for the treatment of AD in adults in many countries, Antonio Torrelo, MD, of the Hospital Infantil Niño Jesús in Madrid, Spain, said at the European Academy of Dermatology and Venereology (EADV) 2022 Annual Meeting. It was approved by the US Food and Drug Administration (FDA) for treating adults with severe alopecia areata in June and is under FDA review for the treatment of AD.
The Phase 3 BREEZE-AD-PEDS Trial
BREEZE-AD-PEDS was a randomized, double-blind trial that evaluated the safety and efficacy of baricitinib in 483 children and adolescents with moderate to severe AD. Participants were aged 2 years to 17 years. Those aged 2 to 5 years had been diagnosed with AD for at least 6 months; if they were older, they had been diagnosed for at least 12 months.
Three dosing levels of baricitinib were tested: 121 patients were given a low dose, which was 0.5 mg/day in children aged 2 to less than 10 years and 1 mg/day in those aged 10 to less than 18 years. A medium dose ―1 mg/day in the younger children and 2 mg/day in the older children ― was given to 120 children, while a high dose ― 2 mg/day and 4 mg/day, respectively ― was given to another 120 children.
Topical treatments were permitted, although for entry into the trial, participants had to have had an inadequate response to steroids and an inadequate or no response to topical calcineurin inhibitors. In all groups, age, gender, race, geographic region, age at diagnosis of AD, and duration of AD "were more or less similar," Torello said.
Good Results, but Only With Highest Dose
The primary IGA endpoint was reached by 25.8% of children in the medium-dose group and by 18.2% in the low-dose group. Neither result was statistically significant in comparison with placebo (16.4%).
When breaking down the results between different ages, "the results in the IGA scores are consistent in both age subgroups ― below 10 years and over 10 years," Torello noted. The results are also consistent across body weights (<20 kg, 20 kg to 60 kg, and >60 kg), he added.
Among those treated with the high dose of baricitinib, Eczema Area and Severity Index (EASI) 75% and 95% improvement scores were reached in 52.5% and 30% of patients, respectively. Corresponding figures for the medium dose were 40% and 21.7%; for the low baricitinib dose, 32.2% and 11.6%; and for placebo, 32% and 12.3%. Again, only the results for the highest baricitinib dose were significant in comparison with placebo.
A similar pattern was seen for improvement in itch, and there was a 75% improvement in Scoring Atopic Dermatitis (SCORAD75) results.
Safety of Baricitinib in Children
The labeling for JAK inhibitors that have been approved to date, including baricitinib, include a boxed warning regarding risks for thrombosis, major adverse cardiovascular events, and all-cause mortality. The warning is based on use by patients with rheumatoid arthritis.
Torello summarized baricitinib's safety profile in the trial as being "consistent with the well-known safety profile for baricitinib in adults with moderate to severe atopic dermatitis."
In the study, no severe adverse effects were noted, and no new safety signals were observed, he said. The rate of any treatment-emergent effect among patients was around 50% and was similar across all baricitinib and placebo groups. Study discontinuations because of a side effect were more frequent in the placebo arm (1.6% of patients) than in the baricitinib low-, medium-, and high-dose arms (0.8%, 0%, and 08%, respectively).
There were no cases of deep vein thrombosis, pulmonary embolism, and other adverse effects of special interest, including major adverse cardiovascular events, gastrointestinal perforations, or opportunistic infections, Torrelo said.
No patient experienced elevations in liver enzyme levels, although there were some cases of elevated creatinine phosphokinase levels (16% in the placebo group and 19% in the baricitinib arms altogether) that were not due to muscle injury. There was a possible increase in low-density cholesterol level (3.3% of those taking placebo, vs 10.1% of baricitinib-treated patients).
Is There a Role for Baricitinib?
"Baricitinib is a potential therapeutic option with a favorable benefit-to-risk profile for children between 2 and 18 years who have moderate to severe atopic dermatitis, and candidates for systemic therapy," Torrelo said. "No single drug is capable to treat every patient with atopic dermatitis," he added in discussing the possible place of baricitinib in pediatric practice.
"There are patients who do not respond to dupilumab, who apparently respond later to JAK inhibitors," he noted.
"We are trying to work phenotypically, trying to learn what kind of patients ― especially children who have a more heterogeneous disease than adults ― can be better treated with JAK inhibitors or dupilumab." There may be other important considerations in choosing a treatment in children, Torrelo said, including that JAK inhibitors can be given orally, while dupilumab is administered by injection.
Asked to comment on the results, Jashin J. Wu, MD, founder and CEO of the Dermatology Research and Education Foundation in Irvine, California, pointed out that "only the higher dose is significantly more effective than placebo."
In his view, "the potentially severe adverse events are not worth the risk compared to more effective agents, such as dupilumab, in this pediatric population," added Wu, who recently authored a review of the role of JAK inhibitors in skin disease. He was not involved with the baricitinib study.
The study was funded by Eli Lilly in collaboration with Incyte Corp. Smith has received grant funding from Merck. Jones has disclosed no relevant financial relationships. Torello has participated in advisory boards and/or has served as a principal investigator in clinical trials for AbbVie, Eli Lilly and Company, Novartis, Pfizer, Pierre Fabre, and Sanofi. Wu has been an investigator, consultant, or speaker for multiple pharmaceutical companies.
European Academy of Dermatology and Venereology (EADV) 2022 Annual Meeting: Late-breaking oral presentation 3447. Presented September 10, 2022.
Sara Freeman is a freelance journalist based in London, England.
Lead image: Eli Lilly
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Cite this: BREEZE-AD-PEDS: First Data for Baricitinib in Childhood Eczema - Medscape - Sep 30, 2022.