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New research indicates that etanercept, a systemic agent, holds promise of treating moderate-to-severe psoriasis in the pediatric population and is a safe option. Clinicians currently use various off-label therapies to treat psoriasis in children and teens, including methotrexate and retinoids. One of the positive outcomes of the study was that patients did not develop a tolerance to therapy. In addition, patients who had been on placebo in the initial phase of the research did improve when they were retreated in an open-label phase of the study with etanercept. Extended follow-up of patients will establish if the therapy is safe for patients to take over the long term.
Salt Lake City-A study using the systemic agent etanercept in children with moderate to severe plaque psoriasis shows that the tumor necrosis factor (TNF) alpha inhibitor is safe and effective in the pediatric population.
The 48-week study, published in January in the New England Journal of Medicine, compared the administration of etanercept to placebo in 211 patients ages 4 to 17.
Specifically, 106 patients were randomized to receive etanercept, and 105 were randomized to receive placebo.
"Pediatric dermatologists see the toughest cases of psoriasis in children, and they are using off-label therapies," says Sheryll Vanderhooft, M.D., a pediatric dermatologist, associate professor of dermatology, and adjunct associate professor of pediatrics at the University of Utah, Salt Lake City.
Children and teens who participated in the study had a score on the Psoriasis Area and Severity Index (PASI) scale of at least 12, with scores ranging from 0 to 72.Higher scores indicated greater disease severity.
Study participants were also evaluated using a static physician's global assessment of at least three, with zero indicating clear and five indicating severe psoriasis. Subjects also had psoriasis that involved at least 10 percent of the body surface area and had a history of the disease for at least six months.
The median PASI score was 16.4, and the median body surface area affected by the condition was 20 percent. Subjects initially received 12 once-weekly subcutaneous injections of placebo or 0.8 mg of etanercept per kilogram of body weight, to a maximum of 50 mg.
In terms of the primary endpoint, investigators found that at 12 weeks, 57 percent of patients who received etanercept reached 75 percent improvement over baseline on the PASI, while just 11 percent who received a vehicle compound reached the same degree of clearance. The difference was statistically significant.
Ian Landells, M.D., one of the study's investigators, says the phenomenon of clearance with etanercept that he witnessed was dramatic.
"There is no drug indicated for the treatment of psoriasis in children," says Dr. Landells, medical director of dermatology at Nexus Clinical Research in St. John's, Newfoundland, Canada, and a clinical assistant professor at Memorial University in St. John's, Newfoundland.
After 12 weeks, researchers began to deliver etanercept in an open-label fashion for 24 weeks. At 36 weeks, a total of 68 percent of patients who initially received etanercept achieved PASI 75, and 65 percent of patients who initially received placebo reached PASI 75.
A 12-week withdrawal, re-treatment period ensued in weeks 37 to 48 to assess the effects of withdrawal of the drug and subsequent re-treatment.
In that time, response was lost by 29 of 69 patients (42 percent), who were assigned to placebo at the second randomization.
Dr. Vanderhooft describes that finding as "disappointing."
"However, it was encouraging that when these patients were re-treated, they improved after four to eight weeks, with responses similar to the original treatment group," Dr. Landells tells Dermatology Times.
Serious adverse events, including an ovarian cyst removal, gastroenteritis and gastroenteritis-associated dehydration, and pneumonia, occurred in three patients during treatment with open-label etanercept. None of the events led to discontinuation of the drug or any sequelae, he says.
The typical approach that clinicians take, particularly with pediatric patients, is to treat their psoriasis and wean them off the medication to minimize side effects, Dr. Vanderhooft says,
and to avoid tachyphylaxis.
"We want to know that if the patients need to be 'rescued' again, that they can be," Dr. Vanderhooft says.
"With topical therapies, we are always trying to maintain an effect, knowing the patient can develop a tolerance to therapy. That tolerance to therapy was not demonstrated in this study," she says.
More research needed
Still, Dr. Vanderhooft says more study on etanercept with larger numbers of patients and longer follow-up would be reassuring.
"We don't know what the long-term effects will be when we treat our pediatric patients with etanercept. We have a much longer track record with agents such as methotrexate, which has well-defined toxicities," she says.
Time will tell if etanercept is an efficacious therapy that can be safely taken by pediatric patients long term, Dr. Vanderhooft says.