Background:
Tumor necrosis factor (TNF) has a pathogenic role in juvenile rheumatoid arthritis. We evaluated the efficacy and safety of adalimumab, a fully human monoclonal anti-TNF antibody, in children with polyarticular-course juvenile rheumatoid arthritis.

Methods:
Patients 4 to 17 years of age with active juvenile rheumatoid arthritis who had previously received treatment with nonsteroidal antiinflammatory drugs underwent stratification according to methotrexate use and received 24mg of adalimumab per square meter of body-surface area (maximum dose, 40mg) subcutaneously every other week for 16 weeks. We randomly assigned patients with an American College of Rheumatology Pediatric 30% (ACR Pedi 30) response at week 16 to receive adalimumab or placebo in a double-blind fashion every other week for up to 32 weeks.

Results:
Seventy-four percent of patients not receiving methotrexate (64 of 86) and 94% of those receiving methotrexate (80 of 85) had an ACR Pedi 30 response at week 16 and were eligible for double-blind treatment. Among patients not receiving methotrexate, disease flares (the primary outcome) occurred in 43% of those receiving adalimumab and 71% of those receiving placebo (P=0.03). Among patients receiving methotrexate, flares occurred in 37% of those receiving adalimumab and 65% of those receiving placebo (P=0.02). At 48 weeks, the percentages of patients treated with methotrexate who had ACR Pedi 30, 50, 70, or 90 responses were significantly greater for those receiving adalimumab than for those receiving placebo; the differences between patients not treated with methotrexate who received adalimumab and those who received placebo were not significant. Response rates were sustained after 104 weeks of treatment. Serious adverse events possibly related to adalimumab occurred in 14 patients.

Conclusions:
Adalimumab therapy seems to be an efficacious option for the treatment of children with juvenile rheumatoid arthritis. (ClinicalTrials.gov number, NCT00048542.) (Figs 1, 2 and Table1).

Table 1: Baseline Demographic and Clinical Characteristics of the Patients* 

Figure 1: Enrollment of Patients and Completion of the Study. (Reprinted from Lovell DJ, for the Pediatric Rheumatology Collaborative Study Group and the Pediatric Rheumatology International Trials Organisation. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008;359:810-820, with permission from the Massachusetts Medical Society. All rights reserved.)

Figure 2: Response to Treatment. Panel A shows American College of Rheumatology Pediatric (ACR Pedi) response levels among patients receiving open-label adalimumab at week 16 according to whether they were or were not receiving methotrexate. ACR Pedi 30, 50, 70, and 90 responses are defined as improvements of at least 30%, 50%, 70%, and 90%, respectively, in at least three of the six core criteria for juvenile rheumatoid arthritis, with worsening of 30% or more in no more than one criterion. Panel B shows the percentages of patients in the placebo and adalimumab groups with disease flare during the doubleblind phase of the study (weeks 16 through 48). Panel C shows ACR Pedi 30, 50, 70, 90, and 100 responses during the first 104 eeks of the open-label extension phase regardless of whether adalimumab was dosed according to body-surface area or body weight. The data are from the intention-to-treat population of 128 patients who entered the open-label extension phase of the study; for missing values, the last observation was carried forward. (Reprinted from Lovell DJ, for the Pediatric Rheumatology Collaborative Study Group and the Pediatric Rheumatology International Trials Organisation. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008;359:810-820, with permission from the Massachusetts Medical Society. All rights reserved.)