ARTHRITIS & RHEUMATISM Vol. 60, No. 9, September 2009, pp 2794–2804 DOI 10.1002/art.24777 © 2009, American College of Rheumatology Long-Term Safety and Effectiveness of Etanercept in Children With Selected Categories of Juvenile Idiopathic Arthritis E. H. Giannini, 1 N. T. Ilowite, 2 D. J. Lovell, 1 C. A. Wallace, 3 C. E. Rabinovich, 4 A. Reiff, 5 G. Higgins, 6 B. Gottlieb, 7 N. G. Singer, 8 for the Pediatric Rheumatology Collaborative Study Group, Y. Chon, 9 S.-L. Lin, 9 and S. W. Baumgartner 9 Objective. This study was undertaken to evaluate the long-term safety and effectiveness of etanercept alone or in combination with methotrexate (MTX) in children with selected categories of juvenile idiopathic arthritis (JIA). Methods. Patients ages 2–18 years with rheuma- toid factor (RF)–positive or RF-negative polyarthritis, systemic JIA, or extended oligoarthritis were eligible for the study. Patients received MTX alone (>10 mg/m 2 / week [0.3 mg/kg/week], maximum dosage 1 mg/kg/ week), etanercept alone (0.8 mg/kg/week, maximum dose 50 mg), or etanercept plus MTX for 3 years in an open-label, nonrandomized study. Safety was assessed by measuring rates of adverse events, and effectiveness was assessed using the physician’s global assessment of disease activity and the pediatric total joint assessment. Results. A total of 197, 103, and 294 patients were enrolled in the MTX, etanercept, and etanercept plus MTX groups, respectively. Exposure-adjusted rates of adverse events were similar among the 3 treatment groups (18.3, 18.7, and 21.6 per 100 patient-years in the MTX, etanercept, and etanercept plus MTX groups, respectively). Respective rates per 100 patient-years of serious adverse events (4.6, 7.1, and 6.0) and medically important infections (1.3, 1.8, and 2.1) were also similar among the 3 treatment groups. Scores for physician’s global assessment and total active joints improved from baseline, and improvement was maintained for the duration of the study. Conclusion. These data confirm the findings of other long-term studies and suggest that etanercept or etanercept plus MTX has an acceptable safety and effectiveness profile in children with selected categories of JIA. Improvement was maintained for 3 years in those continuing to receive medication. Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease (1,2), and it often extends into or relapses during adulthood (3). The pain and functional disability associated with JIA cause a significant burden for patients and their families and caregivers. Indeed, JIA has an important adverse impact on health-related quality of life and well-being that is ClinicalTrials.gov identifier: NCT00078793. Supported by Immunex Corporation, a wholly owned subsid- iary of Amgen Inc., and by Wyeth Pharmaceuticals. 1 E. H. Giannini, DrPH, MSc, D. J. Lovell, MD, MPH: Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio; 2 N. T. Ilowite, MD: Albert Einstein College of Medicine, Bronx, New York; 3 C. A. Wallace, MD: Children’s Hospital and Regional Medical Center, Seattle, Washington; 4 C. E. Rabinovich, MD: Duke University Medical Center, Durham, North Carolina; 5 A. Reiff, MD: Children’s Hospital Los Angeles, Los Angeles, California; 6 G. Higgins, MD, PhD: Ohio State University and Nationwide Children’s Hospital, Columbus, Ohio; 7 B. Gottlieb, MD, MS: Schneider Children’s Hospital, New Hyde Park, New York; 8 N. G. Singer, MD: University Hospitals Case Medical Center, and University Hospitals Rainbow Babies & Chil- dren’s Hospital, Cleveland, Ohio; 9 Y. Chon, PhD, S.-L. Lin, MD, PhD, S. W. Baumgartner, MD: Amgen Inc., Thousand Oaks, California. Dr. Giannini received grant support from Amgen to serve as Principal Investigator of this study (more than $10,000). Dr. Ilowite has received consulting fees, speaking fees, and/or honoraria from Novartis, Bristol-Myers Squibb, and Abbott (less than $10,000 each). Dr. Lovell has served on the Amgen speaker’s bureau. Dr. Wallace has received a grant from Amgen (more than $10,000). Dr. Reiff has received consulting fees, speaking fees, and/or honoraria from Amgen and Wyeth (more than $10,000 each) and has provided expert testi- mony on behalf of Amgen, Wyeth, Pfizer, and Merck. Dr. Singer has received consulting fees, speaking fees, and/or honoraria from Acu- mentis, CME Solutions, and the Vienna Medical Academy (less than $10,000 each) and from Abbott Immunology (more than $10,000). Drs. Chon, Lin, and Baumgartner own stock or stock options in Amgen. Address correspondence and reprint requests to E. H. Gian- nini, DrPH, MSc, Pediatrics and Rheumatology/Pav 2-129, Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229. E-mail: Edward.Giannini@cchmc.org. Submitted for publication December 23, 2008; accepted in revised form June 1, 2009. 2794