PracticalDermatology

Starting about eight decades ago with the emergence of hydrocortisone, a new intervention for eczema has emerged roughly every 20 years. Dermatologists welcomed topical calcineurin inhibitors in the early 2000s, observed Richard Antaya, MD during a lecture at the Society for Pediatric Dermatology’s 2022 Pre-AAD Meeting, held live in Boston in March. Today, the biologics and JAK inhibitors are the focus of innovation.

In recent years, IL-4 and IL-13 have been implicated as central to the pathogenesis of AD, contributing to epidermal barrier dysfunction, inflammation, immune dysregulation, and itch, Dr. Antaya notes. Dupilumab (Dupixent, Sanofi and Regeneron), the first biologic approved to treat AD, inhibits IL4 and 13. It is approved for children 6 months through to adulthood.

Data presented at the Revolutionizing Atopic Dermatitis (RAD) Conference by Paller et al show that, among subjects aged 6 months to 5 years who used dupilumab every four weeks (200mg or 300mg, based on body weight) with or without low-potency topical corticosteroids (TCS), 28% achieved clear or almost-clear skin compared to 4% with placebo at 16 weeks. Just over half (53%) of treated subjects achieved 75% or greater improvement in overall disease severity from baseline compared to 11% with placebo, and 48% achieved clinically meaningful reduction in itch compared to 9% with placebo.

The safety profile observed through 16 weeks was similar to the safety profile in patients 6 years and older with AD. Development of psoriasiform dermatitis during dupilumab treatment has been reported in children and adolescents, most of which cleared with TCS. A greater number of such eruptions have been reported in adults using dupilumab.

Tralokinumab (Adbry, LEO Pharma) binds IL-13 and is FDA approved for treatment of adults with AD. The ECZTRA 6 trial investigated the safety and efficacy of tralokilumab 150mg (n=98) or 300mg (n=97) every 2 weeks compared to placebo (n=94) in adolescents; FDA submission is anticipated.

At week 16, 21.4% of the tralokinumab 150mg group and 17.5% of the tralokinumab 300mg group achieved clear or almost-clear skin compared to 4.3% with placebo. Additionally, 28.6% of the tralokinumab 150mg group and 27.8% of the tralokinumab 300mg group achieved EASI-75 or greater disease improvement from baseline compared to 6.4% with placebo.

Overall frequency and severity of adverse events in the trial were comparable across treatment groups over 16 weeks.

Dr. Antaya notes that the baseline characteristics of the study groups in the tralokinumab and dupilumab adolescent trials were similar, allowing for a reasonable comparison of results. Efficacy results are similar for both treatments.

JAK inhibitors are perhaps, “the hottest topic in atopic dermatitis,” Dr. Antaya says. “JAKs are involved in everything.”

Ruxolitinib cream 1.5% (Opzelura, Incyte) is FDA approved for the short-term and non-continuous chronic treatment of mild to moderate AD in patients 12 and older. It was studied in 1,249 subjects, of whom 245 were adolescents. Roughly 50% of treated subjects were clear or almost clear at week eight. Significantly more patients treated with Opzelura experienced a clinically meaningful reduction in itch from baseline at week eight, as measured by a ≥4-point reduction in the itch Numerical Rating Scale (itch NRS4).

Patients must not apply more than 60g per week; absorption studies show potential systemic complications with such dosage, primarily in adults. Dispensed in a 60g tube, the drug is not likely to be applied at more than 60g per week.

Upadacitinib (Rinvoq, AbbVie) is an oral JAK inhibitor approved for use in adolescent patients (Read more on p. 26). In trials, 40 to 70% of subjects receiving upadacitinib were clear or almost clear and 70 to 80% achieved EASI-75.

A comparison of trial data for adults suggests a slight advantage for upadacitinib in terms of itch reduction and clinical improvement, compared to dupilumab, Dr. Antaya says.

Both topical and oral JAKs have been associated with development of acne. “Clearly there is a signal there for both lower and higher dose medicines,” Dr. Antaya says. “It’s omething to think about if we are treating teenagers.”

Both topical and oral JAKs have boxed warnings about increased risk of serious heart-related events, cancer, blood clots, and death. Prescribers must be aware of these and counsel patients appropriately.

In the pipeline for pediatric atopic dermatitis are inhibitors of IL-13 and IL-31 as well as the JAK inhibitor baricitinib, Dr. Antaya notes.