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Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy inA Children With Polyarticular Forms of Juvenile IdiopathicA Arthritis With Clinically Inactive Disease. Arthritis Rheumatol 2018 09;70(9):1508-1518



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-85052490977   12 Citations


OBJECTIVE: To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated a?Y6 months of continuous clinically inactive disease.

METHODS: In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare.

RESULTS: Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving 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 (37%) of 106 patients by 8 months. The mean/median A? SEM time to flare was 212/250 A? 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05).

CONCLUSION: Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.

Author List

Lovell DJ, Johnson AL, Huang B, Gottlieb BS, Morris PW, Kimura Y, Onel K, Li SC, Grom AA, Taylor J, Brunner HI, Huggins JL, Nocton JJ, Haines KA, Edelheit BS, Shishov M, Jung LK, Williams CB, Tesher MS, Costanzo DM, Zemel LS, Dare JA, Passo MH, Ede KC, Olson JC, Cassidy EA, Griffin TA, Wagner-Weiner L, Weiss JE, Vogler LB, Rouster-Stevens KA, Beukelman T, Cron RQ, Kietz D, Schikler K, Schmidt KM, Mehta J, Wahezi DM, Ting TV, Verbsky JW, Eberhard BA, Spalding S, Chen C, Giannini EH


James J. Nocton MD Professor in the Pediatrics department at Medical College of Wisconsin
James Verbsky MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antirheumatic Agents
Arthritis, Juvenile
Child, Preschool
Drug Therapy, Combination
Induction Chemotherapy
Life Tables
Proportional Hazards Models
Prospective Studies
Risk Factors
Symptom Flare Up
Time Factors
Treatment Outcome
Tumor Necrosis Factor-alpha
Withholding Treatment