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 Inactive Disease

Abstract

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 ≥6 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 ± SEM time to flare was 212/250 ± 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.

Trial registration: ClinicalTrials.gov NCT00792233.

Figure 1

Patient Disposition.

Figure 2

Kaplan-Meier Curves by 8 months of prospective observation in patients in JIA patients in clinical inactive disease (CID) who withdrew anti-TNF therapy. Patient visits were censored at 8 months follow-up even though some patients were followed longer than 8 months. Figure A shows the flare rate in the overall population who withdrew therapy. Figure B shows comparison of flare rates in those with and without background methotrexate therapy. Figure C shows comparison of flare rates of several types of anti-TNF therapy. Figure D shows flare rates of various JIA categories.