Dr. Richard Antaya discusses new therapeutic options for treating atopic dermatitis and psoriasis in the pediatric population.
Richard J. Antaya, MD, FAAD, is Professor of Dermatology, Pediatrics, and Nursing, Yale University School of Medicine, New Haven, Connecticut, and member of the Society for Pediatric Dermatology.
“In the last two years, we have five new medications or new indications of previously licensed medications for children,” said Richard Antaya, MD, FAAD, who presented “The Big Bang: The Expanding Universe of Therapeutics for Pediatric Skin Disease” at the Society for Pediatric Dermatology’s 34th Annual Pre-AAD Meeting in Boston.
“Atopic dermatitis is the single most common inflammatory disease after acne, and it really has a major negative impact on children’s lives. Psoriasis also can severely negatively impact children’s lives. We now have several new options for both diseases, instead of relying on nonspecific systemic immunosuppressants and phototherapy. While these worked reasonably well, they are not as safe or effective as these newer agents.”
Those five medications include ixekizumab, secukinumab, tralokinumab, ruxolitinib, and upadacitinib.
IL-17 Inhibitors for Psoriasis
“For childhood psoriasis, ixekizumab was released in 2020 and secukinumab was released in 2021.”
The IL-17 inhibitors are indicated in children 6 years of age and older with moderate to severe psoriasis. Guselkumab, an IL-23 inhibitor, for 6 years of age and older is currently in phase 3 trials.
“Both IL-17 inhibitors are extremely effective for treating and clearing moderate to severe psoriasis…. Neither require as much lab monitoring as our current systemic immunosuppressants and there’s less organ-specific toxicity with these biologics. So that’s great compared to cyclosporine or methotrexate, upon which we have historically relied.”
Therapeutics for Atopic Dermatitis
For atopic dermatitis, dupilumab has been a gamechanger for children 6 and older.
“…before dupilumab for adolescents, the last addition to our therapeutic arsenal was topical Eucrisa ointment, or crisaborole, for children with mild to moderate atopic dermatitis, and that was over six years ago.”
According to Dr. Antaya, the FDA may be expanding the dupilumab label to include infants as young as 6 months of age.
“Then dupilumab will be available for atopic dermatitis from infancy through adulthood.”
Tralokinumab, an anti-IL 13 antibody for atopic dermatitis, was approved for adults last year. Approval for children 12 and older is on the horizon, said Dr. Antaya.
Other therapeutics for atopic dermatitis currently available are the JAK inhibitors ruxolitinib cream and oral upadacitinib, both indicated in children 12 years of age and older, for the treatment of mild to moderate and moderate to severe refractory atopic dermatitis, respectively.
“Ruxolitinib cream is the first in its class for a topical JAK inhibitor for any indication, but now indicated for patients 12 years and above for atopic dermatitis, which is a very welcome addition.”
The oral JAK 1/2 inhibitor upadacitinib is indicated for adolescents who have failed previous systemic medication including biologics, said Dr. Antaya.
“It’s a giant step up from what we’ve had previously.”
Cautionary Caveats
Until long-term safety data is available, approach these newer treatments with caution, said Dr. Antaya.
“We have safety data over a year or two, but we really don’t know how these are going to affect our patients throughout their lifetime. Psoriasis and atopic dermatitis are both chronic, lifelong diseases. There also seems to be a signal for inflammatory bowel disease (IBD) with the IL-17 inhibitors, maybe more so in children. It’s well documented in adults, but in the phase 3 trials, there were increased incidences of IBD, which is also a chronic, lifelong disease, and we prefer not to add a chronic disease to control another. We must carefully observe for this moving forward.”
For atopic dermatitis, dupilumab has been life-changing for children and adults but has been associated with new onset psoriasis, said Dr. Antaya.
“Our patients with atopic dermatitis are benefiting from such an effective therapy. Th2 immunosuppression, unlike Th1 suppression for psoriasis, does not affect the arm of the immune system that protects against viral, bacterial, and fungal infections. So these biologics appear to be safer in that regard.”
“One caveat, previously in the adult literature and most recently reported in the pediatric literature, is the emergence of psoriasis in patients receiving the Th2 inhibitor dupilumab.”
According to Dr. Antaya, it may be the result of a shift from the Th2 to the Th17/IL-23 arm of the immune system and something to discuss with patients before prescribing dupilumab or tralokinumab, once it’s indicated for children.
“Tralokinumab may soon be another option for our adolescent AD patients. I think it looks (at least from the phase 3 data) fairly similar to dupilumab. [It] may have a lower risk of conjunctivitis… [and offer] another alternative in patients who are not responding to dupilumab.”
Ruxolitinib cream also comes with a caveat, said Dr. Antaya. While it is a unique mono- or add-on therapy for patients who have poorly controlled focal atopic dermatitis, with few application-site adverse events, in the maximum use studies, systemic absorption approached that of oral ruxolitinib in the adult population, said Dr. Antaya. Systemic levels were not as great in the adolescents, however.
“So ruxolitinib cream seems appropriate for focal areas of AD. It is not recommended for more than 10% of the body surface area. In addition, it carries the black box warning similar to other oral JAK inhibitors.”
There are many more therapeutics on the horizon, particularly with biologics and JAK inhibitors for psoriasis and AD, said Dr. Antaya.
“…these new biologics may be beneficial in decreasing associated comorbidities with psoriasis—arthritis, hypertension, metabolic disease, maybe even mental health associations like depression. We don’t know. But that’s certainly something that’s going to be evaluated long term as long-term psoriasis control improves.”
“It is a new era for children with severe inflammatory skin disease. We have so much more to offer and there’s going to be more…. I think we are in the beginning of the bang.”
