ORLANDO – Because Food and Drug Administration–approved treatment options formedications. However, this scenario is changing, A. Yasmine Kirkorian, MD, said at the ODAC Dermatology, Aesthetic & Surgical Conference.
“I really would like to emphasize that children with severe disease need to be treated,” added, a pediatric dermatologist at George Washington University, Washington, and Children’s National Health System, where she is interim chief of the division of dermatology.
Current on-label systemic therapies for pediatric skin disease include etanercept for psoriasis (4 years and older), ustekinumab for psoriasis (12 years and older), adalimumab for hidradenitis suppurativa (12 years and older), and omalizumab for chronic idiopathic urticaria (12 years and older). A new addition to the list is dupilumab, which was approved for children and adolescents with atopic dermatitis (AD) aged 12 years and older in 2019, she noted.
Dupilumab is currently being studied in children aged 6 months to 12 years, and other clinical trials are evaluating more options for pediatric patients with AD, alopecia areata, and psoriasis. They include a clinical trial of the oral Janus kinase 3 (JAK3) inhibitor PF-06651600 in patients aged 12 years and older with alopecia areata. Six biologic therapies are being evaluated for psoriasis in patients beginning at 6 years: ixekizumab, secukinumab, ustekinumab, guselkumab, brodalumab, and apremilast.
Some systemic therapies are off-label “but used all the time” for dermatologic diseases in pediatrics, Dr. Kirkorian noted. One example is methotrexate, which is approved by the FDA for acute lymphoblastic leukemia, meningeal leukemia, and juvenile idiopathic arthritis down to infancy. Having existing efficacy and safety data for a medication in a pediatric population, even for a different disease, can be helpful when counseling parents of children with severe dermatologic disease. “If you have something, even in an older population of children, it can be reassuring, or you can use evidence from other diseases,” she said.
While methotrexate is a cheap option and approved by the FDA for other pediatric indications down to infancy, the cons of using it to treat AD in pediatric patients are numerous. Treatment requires a number of blood draws for lab testing, which can be discouraging for younger patients, and the reported adverse effect profile may be concerning to some parents, while “in practice doesn’t really occur,” she said. Methotrexate is a teratogen so is not appropriate for teenagers who are sexually active and not using contraception.
The “biggest problem,” though, is the issue of whether methotrexate is effective, since it doesn’t always work for AD, Dr. Kirkorian said. “Even at the highest doses, I often feel that we fail the atopic children,” as opposed to using it to treat psoriasis, “where you know I’m going to get you on something that works.”
In contrast, cyclosporine is FDA approved down to infancy, and works quickly as a bridge to other therapy, and is not expensive, Dr. Kirkorian said. Cons include the need for blood draws, blood pressure checks, drug interactions, and adverse effects, she noted, adding that she tries to use cyclosporine as a bridge to on-label and off-label dupilumab.
Even with FDA approval for dupilumab down to age 12 years, she said it can be difficult to get insurance approval for the on-label treatment for patients in this age group with AD, before they first fail other therapies (even with off-label systemic drugs). For patients under age 12 years, getting approval is even more challenging and requires rigorous documentation of what therapies the child has failed, and how it has affected their quality of life, she said.
“If you send in a letter to the insurance company without an IGA [Investigator Global Assessment] or SCORAD, you’re going to get rejected,” Dr. Kirkorian said. In addition to those two measures, she provides “everything else,” including the impact of the disease on quality of life of patients, and school, she said, adding, “Did they miss school, did they get hospitalized for infections? And do they have comorbid diseases that might help you get approval?”
In pediatric patients with psoriasis, common issues are more likely to be about how insurance dictates step therapy. She has often found that young children may stop responding to etanercept after a few years, which can justify a switch to ustekinumab or a new treatment in a clinical trial, she said. Adolescents with psoriasis can receive ustekinumab, which is approved for psoriasis in patients aged 12-17 years, she said, noting that the infrequent ustekinumab dosing schedule is often beneficial in this population.
When all other approved options fail for young patients with psoriasis, justifying off-label use isn’t always easy. “You just have to make a justification based on the literature, even though it’s off label,” citing available safety information for other diseases, and “demonstrate over and over the impact on quality of life,” which works “most of the time,” Dr. Kirkorian said.
She reported having no conflicts of interest.