Adalimumab with or without methotrexate in juvenile rheumatoid arthritis.

Abstract

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 24 mg of adalimumab per square meter of body-surface area (maximum dose, 40 mg) 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.)

• Authors: Daniel J Lovell, Nicolino Ruperto, Steven Goodman, Andreas Reiff, Lawrence Jung, Katerina Jarosova, Dana Nemcova, Richard Mouy, Christy Sandborg, John Bohnsack, Dirk Elewaut, Ivan Foeldvari, Valeria Gerloni, Jozef Rovensky, Kirsten Minden, Richard K Vehe, L Wagner Weiner, Gerd Horneff, Hans-Iko Huppertz, Nancy Y Olson, John R Medich, Roberto Carcereri-De-Prati, Melissa J McIlraith, Edward H Giannini, Alberto Martini, Pediatric Rheumatology Collaborative Study Group, Pediatric Rheumatology International Trials Organisation
• Journal: The New England journal of medicine (N Engl J Med) Vol. 359 Issue 8 Pg. 810-20 (Aug 21 2008) ISSN: 1533-4406 [Electronic] United States
• PMID: 18716298 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: 2008 Massachusetts Medical Society

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Tumor Necrosis Factor-alpha
• Adalimumab
• Methotrexate

Topics

• Adalimumab
• Adolescent
• Antibodies, Monoclonal (administration & dosage, adverse effects, immunology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents (administration & dosage, adverse effects, therapeutic use)
• Arthritis, Juvenile (drug therapy)
• Child
• Child, Preschool
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Male
• Methotrexate (therapeutic use)
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)