Drug Updates

Using biologics in young patients raises a number of concerns for some clinicians, including questions of infection risks, possible risks of malignancy, long-term surveillance to prevent malignancy, possible neurologic side effects, and response to vaccinations. Treating these patients requires a careful risk–benefit evaluation throughout therapy. In addition, adult guidelines for tuberculosis screening with purified protein derivative prior to commencing biologic agents are recommended.

Current Agents

• Etanercept is FDA approved for treating moderate to severe polyarticular-course JIA in patients two years of age and older.¹¹ The approved dose for this tumor necrosis factor (TNF)–α antagonist in this population is 0.8 mg/kg per week subcutaneously as a single or divided dose (maximum weekly dose of 50 mg). The 50-mg prefilled syringe or SureClick autoinjector can be used for pediatric patients weighing 139 pounds or more (the 25-mg prefilled syringe is not recommended for patients weighing less than 68 pounds. Glucocorticoids, NSAIDs, or other analgesics may be continued while using etanercept. When using two subcutaneous injections a week, the injections should either be given on the same day or three or four days apart. In Dutch and German registries, the agent has shown good short-term safety and tolerability in patients with JIA.⁹ Additionally, patients who have received etanercept for more than eight years in clinical trials also have had a good response.

In February 2008, adalimumab received FDA approval for the treatment of moderate to severe active polyarticular JIA in patients age four years and older.¹² The approved dosing for this TNF-α antagonist in four- to 17-year-olds is 20 mg subcutaneously every other week (20-mg prefilled syringe) for patients that weigh 33 to 66 pounds, and a dose of 40 mg subcutaneously every other week for patients that weigh 66 pounds or more (Humira Pen or 40-mg prefilled syringe).¹³

Infliximab is not approved by the FDA for use in JIA patients; however, it is approved for treating pediatric Crohn’s disease in patients at least six years old or older. Therefore, there has been some use of infliximab in JIA, such as that reported by Rupert et al.¹⁴ In this study, 122 patients’ refractory to methotrexate (MTX) treatment were treated with infliximab 3 mg/kg/dose as an IV infusion plus MTX or placebo plus MTX for 14 weeks. They then received either infliximab 3 mg/kg/dose or 6 mg/kg/dose through Week 44. Once all patients were receiving infliximab, the ACR Pedi 30 response rate was 73%. The agent was generally well tolerated, but patients that received the higher dose tolerated the drug better. There were more serious infections and infusion reactions (e.g., vomiting, headache, fever, and hypotension) in the lower dosage–treated group. Anti-infliximab antibodies were also reported. Some of the infections included upper respiratory tract infections, herpes zoster, asymptomatic pulmonary tuberculosis, and pneumonia. Infusion reactions leading to drug discontinuation have been reported elsewhere and hinder appropriate management.⁹ Postmarketing surveillance in pediatric patients using TNF-α antagonists shows an increased risk of abscess formation and sepsis.