Advances in pediatric inflammatory skin disease

After having endured nearly 15 years without any new therapeutic agents for pediatric inflammatory skin disease, there is now exciting research that will change treatment imminently and into the future, according to a presenter at the Fall Clinical Dermatology Conference in October in Las Vegas.

For example, one recent study found that babies born with skin barrier dysfunction measured as increased transepidermal water loss had higher rates of the development of atopic dermatitis (AT). Another study indicates that frequent use of emollients in babies may prevent AD.  

Dr. Eichenfield“Can we start to decrease our high rates of AD by some early interventions, either identifying patients at risk and frequent moisturizers or potentially changing the bacteria on their skin or their exposure to microbes, which might influence the development of AD?” says Lawrence F. Eichenfield, M.D., a professor of dermatology and pediatrics at the University of California, San Diego, who notes that the prevalence of AD is 12% to 15% in the first years of life.

AD is also associated with other significant comorbidities, including food allergy, asthma and allergic rhinitis, “so there is a cost multiplier,” Dr. Eichenfield tells Dermatology Times in a post-conference interview. He is chief of pediatric dermatology at Rady Children’s Hospital in San Diego.

Topical therapies

Within the next few months, the topical anti-inflammation medicine crisaborole (Anacor/Pfizer) should become FDA-approved. This nonsteroidal agent is based on blocking phosphodiesterase 4 (PDE4), “which 30 years ago was found to increase in inflammatory cells in AD,” says Dr. Eichenfield. “PDE inhibitors influence release of cytokines, which influence inflammation in the skin.”

The boron-based inhibitor in ointment form (crisaborole 2%) has completed phase 3 testing, as well as long-term one-year studies. The product is used twice daily day for inflammatory eczema.

“Crisaborole has been shown to work better than its vehicle to decrease itch fairly promptly,” Dr. Eichenfield says. Also, a 48-week safety study (after phase 3) found the medicine to be very well tolerated, without any significant systemic side effects.

“There are other topicals that are starting phase 3 studies, which could increase our armamentarium of therapies for eczema,” Dr. Eichenfield says. “However, a huge evolution and revolution in therapy for AD will revolve around systemic products.”

Although children were not involved in the initial systemic studies for eczema, “they are now being studied,” he says.

Biologic coming

The injectable dupilumab (Regeneron Pharmaceuticals) will presumably be the first biologic approved for AD. “Phase 3 studies in adults with moderate to severe AD show tremendous success, with patients achieving marked improvement in their eczema compared to placebo, in a variety of dosing regimens,” Dr. Eichenfield says. “There is also seemingly good safety, other than some conjunctivitis observed.”

Because of advocacy efforts in advance of these studies, the FDA and the European Medicines Agency (EMA) “have welcomed pediatric studies, which have already begun in Europe and are about to start in the United States for children and adolescents,” Dr. Eichenfield says.

The FDA is evaluating adult data on dupilumab and is expected to respond early next year.

“If all goes well, the biologic could be commercially available for children by 2018,” Dr. Eichenfield says.

The current protocol for adults is monthly injections over several months. “However, the duration of treatment that would be needed for efficacy in children is unknown,” Dr. Eichenfield says.

Food allergies, AD

For AD itself, there has always been a link with food allergy, especially in children.

“In the past, people attempted to avoid allergenic foods to prevent food allergy, but that methodology has been abandoned, based on a variety of recent studies that have shown early feeding of some allergenic foods can prevent food allergy,” Dr. Eichenfield says.

Pending guidelines from the National Institutes of Health (NIH) will state that children in the first year of life with severe eczema and/or egg allergy “is the group that has the highest risk of developing peanut allergy and will be advised to undergo screening either with allergy referral or with screening blood work to determine if these patients can safely engage in early feeding to try to prevent peanut allergy,” Dr. Eichenfield says.

Psoriasis in kids

Pediatric psoriasis is another area of interesting research. Psoriasis is associated with much higher rates of cardiovascular disease, including early myocardial infarction at age 30 or over.

“There are now studies that show children with psoriasis possess some of these same risk factors, including higher rates of obesity, some changes in insulin level and changes in their ability to handle cholesterol,” Dr. Eichenfield says. “Therefore, more aggressive treatment of psoriasis in children could minimize its health effects.”

Although there are no systemic therapies for pediatric psoriasis approved in the Unites States, “the FDA has signaled that it is considering approving biologic agents,” says Dr. Eichenfield, noting that historically America has lagged behind Europe, which has already approved etanercept, ustekinumab and adalimumab.

“We know how significant these inflammatory diseases are in the life of the affected children and adolescents,” Dr. Eichenfield says. “After many years of frustration in not having new therapies to help better treat these patients, this is a tremendously exciting time.”