Safety and Efficacy of High-dose Tumor Necrosis Factor (TNF) Inhibitors in the Management of Pediatric Inflammatory Diseases

Abstract

Objectives: To review a cohort of patients receiving higher than standard or FDA approved dosing of TNF inhibitors to assess the safety and efficacy of these agents in the management of inflammatory joint and eye disease in a clinical pediatric rheumatology setting. Methods:A retrospective review was performed of patients 1-17 years of age with inflammatory diseases requiring TNF inhibitor therapy treated with at least six weeks of treatment of a higher than the standard FDA approved dose of TNF inhibitors, from 12/1/11-4/8/14. Entanercept (Enbrel) was given at doses greater than 0.8 mg/kg, Infliximab (Remicade) was infused in doses greater than 5 mg/kg or more frequently than every eight weeks, and Adalimumab (Humira) was given at either 20 mg/kg weekly for patients weighing less than 30 kg or 40 mg/kg weekly for patients weighing greater than 30 kg. Serious adverse events (SAE), infections, and infusion reactions were all documented. We also noted clinical improvement based on parent/patient's report of decreased symptoms and provider assessment, including exam findings and laboratory parameters. Results:Thirty-five patients were included (average 11.3 years). Of these, 24 (68%) were noted to have improvement of either symptoms or exam. There was one SAE noted in the group and one infusion reaction, and 10 patients with illnesses that may have been exacerbated by immune suppression. Conclusion:Higher than standard-dose or FDA approved dosing of TNF inhibitors appear safe and efficacious in the management of pediatric inflammatory diseases, however, caution must be taken with interpretation of the results due to the retrospective chart review study design. Larger, prospective, controlled studies will be necessary to more fully evaluate safety and efficacy of this treatment approach.