CHICAGO, Illinois—The TNF blocker etanercept (Enbrel®) reduces disease severity in children and adolescents with moderate-to-severe plaque psoriasis, and improvements are evident as early as the second week of therapy, according to new research in the January 17, 2007 issue of the New England Journal of Medicine.¹ There is currently no systemic therapy approved for children and adolescents with this debilitating skin condition.

"The results of this study implicated TNF in the pathogenesis of pediatric psoriasis and demonstrated that etanercept significantly reduced disease severity," reported lead researcher Amy S. Paller, MD, of Children's Memorial Hospital and Northwestern University Medical School in Chicago.

Primary endpoint was PASI 75 at week 12

In the 48-week double-blind study, 211 psoriasis patients aged 4 to 17 were randomly assigned to 12 once-weekly subcutaneous injections of placebo or 0.8 mg of etanercept per kilogram of body weight (to a maximum of 50 mg). This study was followed by a 24-week open label trial of once-weekly etanercept. At week 36, a total of 138 patients underwent a second randomization to placebo or etanercept to determine the effects of withdrawal and re-treatment.

At week 12, 57% of patients who received etanercept achieved PASI 75, compared with 11% of those receiving placebo (P <.001). Improvements were evident as early as week 2, and significant differences were seen as early as week 4, the study showed. Moreover, 75% of patients taking etanercept achieved PASI 50 at 12 weeks, compared with 23% of their counterparts who received placebo. Additionally, 27% of patients in the etanercept group achieved PASI 90, compared to 7% in the placebo group. Fully 53% of patients who took etanercept also received a physician's global assessment of clear or almost clear at week 12, compared with 13% of patients who took placebo.

At week 36, after 24 weeks of once-weekly open-label etanercept therapy, 68% of patients who initially received etanercept achieved PASI 75 as did 65% of those who were initially randomized to placebo. Patients withdrew from therapy during week 36 to 48. The response was lost by 42% of these patients who were assigned to placebo at the second randomization.

Short-term safety looks good

Three patients experienced four serious adverse events, three of which were infectious in origin. All adverse events occurred in the patients when they were receiving open-label treatment and all resolved without further incident.

While more study is needed to assess the safety of etanercept in this population, studies of the use of this drug in children and adolescents with polyarticular juvenile rheumatoid arthritis for up to 8 years prove reassuring regarding safety, the study authors note.

Translating research into practice

Musculoskeletal Report asked two leading pediatric rheumatologists, Yukiko Kimura, MD, chief of pediatric rheumatology and her colleague Kathleen A. Haines, MD, section chief of pediatric immunology in the department of pediatric rheumatology and immunology, both at the Joseph M. Sanzari Children's Hospital at Hackensack University Medical Center in New Jersey, to comment on how the new study could affect practice and the growing role that biologics are having in pediatric disease.

Dr. Kimura pointed out that pediatric rheumatologists do see patients who have psoriatic arthritis and that they do treat them with etanercept, but they do not treat patients who have psoriasis alone.

"Judging by the way patients with psoriatic arthritis respond to other TNF-blockers, I would imagine it would be the same [in plaque psoriasis]," she said. Going forward, "I am sure there will be more applications for biologics in pediatric rheumatic diseases as we expand our understanding of the pathophysiology of these diseases."

Dr. Haines agreed. "If someone with psoriatic arthritis is referred I still use methotrexate first, partly due to the long experience we have and partly due to the fact insurance companies usually require treatment failures with methotrexate before they will go to a biologic. I'm still pleasantly surprised at the short-term safety of these biologics [and] time will tell re[garding] long-term safety."

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