Biologic safety remains uncharted territory for pediatrics

Denver - Biologic drugs are being extensively explored in medicine, but their use in pediatric patients remains uncharted territory, according to an expert who spoke at the 72nd Annual Meeting of the American Academy of Dermatology.

When it comes to the safety of biologic drugs, says Amy Paller, M.D., "We have so much less to say in children. The world of biologics in children is largely unexplored." She is professor and chair of dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine, Chicago.

The only randomized, double-blinded, controlled trial with a biologic drug for psoriasis in children in the United States showed etanercept to be safe and effective in this population (Paller AS, Siegfried EC, Langley RG, et al. N Engl J Med. 2008;358(3):241-251). After 12 weekly injections of study drug or placebo, 57 percent of patients in the treated group reached PASI 75, versus 11 percent in the placebo group (p <0.001).

Accordingly, the drug is approved in Europe for ages 8 and up, and used extensively in children in the United States, though not approved for this indication, Dr. Paller says. Nor are any other biologic drugs approved by the Food and Drug Administration for pediatric psoriasis.

Nevertheless, "There are some exciting studies going on now, and at this time next year there may be some data to present."

Particularly exciting, Dr. Paller says, are an ongoing comparison of the efficacy and safety of adalimumab versus methotrexate, and a similar phase 3 study of ustekinumab versus methotrexate (both outside the United States).

Dermatologists have growing experience with adalimumab in children, particularly adolescents, she adds.

"There are very few reported cases. We tend to use a maximum of about 40 mg. It can also be effective for pustular psoriasis when other TNF (tumor necrosis factor) inhibitors fail," she says.

Conversely, Dr. Paller says, dermatologists rarely use infliximab in children. "Mostly it's been used to try to get more acute, rapid control, particularly with progressive pustular psoriasis."

Similarly, "Ustekinumab is rarely used in pediatrics," she says. Nevertheless, Dr. Paller says she hopes dermatologists will consider the drug for children who present with psoriasis or symptoms that look like pityriasis rubra pilaris, perhaps with a family history. Such patients may have a CARD14 mutation, which contributes to increased expression of interleukin-23, she says.

"This group of patients often doesn't respond well to topicals or traditional TNF inhibitors, and sometimes responds to methotrexate. However, we have found this group responds quite well to ustekinumab," Dr. Paller says.