Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti–Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically…

Daniel J. Lovell, Anne L. Johnson, Bin Huang, Beth S. Gottlieb, Paula W. Morris, Yukiko Kimura, Karen Onel, Suzanne C. Li, Alexei A. Grom, Janalee Taylor, Hermine I. Brunner, Jennifer L. Huggins, James J. Nocton, Kathleen A. Haines, Barbara S. Edelheit, Michael Shishov, Lawrence K. Jung, Calvin B. Williams, Melissa S. Tesher, Denise M. Costanzo, Lawrence S. Zemel, Jason A. Dare, Murray H. Passo, Kaleo C. Ede, Judyann C. Olson, Elaine A. Cassidy, Thomas A. Griffin, Linda Wagner‐Weiner, Jennifer E. Weiss, Larry B. Vogler, Kelly A. Rouster‐Stevens, Timothy Beukelman, Randy Q. Cron, Daniel Kietz, Kenneth Schikler, Kara M. Schmidt, Jay Mehta, Dawn M. Wahezi, Tracy V. Ting, James W. Verbsky, B. Anne Eberhard, Steven Spalding, Chen Chen, Edward H. Giannini

Determine the frequency, time-to-flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (PF-JIA) who demonstrated ≥ 6 continuous months of clinical inactive disease (CID). In 16 centers 137 patients with PF-JIA in CID on anti-TNF therapy (42% of whom were also on methotrexate [MTX]) were prospectively followed. If CID was maintained for the initial 6 months on study anti-TNF was stopped and patients assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table, t-tests, Chi square, and Cox regression analyses were used to identify independent variables that could significantly predict flare by 8 months or time-to-flare. 106/137 (77%) maintained CID on anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39/106 (37%) patients by 8 months. The mean/median time-to-flare were 212/250 (SEM 9.77) days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing CID, and shorter time from onset of CID to enrollment were found to have significantly lower hazard ratios (p< 0.05) for likelihood of flare by 8 months. Over one-third of patients with PF-JIA in sustained CID will flare by 8 months following discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified. This article is protected by copyright. All rights reserved.