Flare Risk Examined in Juvenile Idiopathic Arthritis After Anti-TNF Therapy Discontinuation

More than one-third of patients with polyarticular forms of juvenile idiopathic arthritis (JIA) with sustained clinical inactive disease are expected to have a flare by 8 months after the discontinuation of anti-tumor necrosis factor (TNF) therapy, according to the results of a study published in Arthritis Rheumatology.

Daniel J. Lovell, MD, MPH, of the Cincinnati Children’s Hospital Medical Center in Ohio, and colleagues conducted a prospective trial in 16 centers, involving 137 patients with polyarticular forms of JIA with clinically inactive disease who were receiving anti-TNF therapy (42% were also on methotrexate). Anti-TNF therapy was stopped if clinically inactive disease was maintained for the initial 6 months of the study, and patients were then assessed for flare at 1, 2, 3, 4, 6, and 8 months. The investigators used life-table, t-tests, Chi square, and Cox regression analyses to identify independent variables that could significantly predict flare by 8 months or time to flare.

Clinically inactive disease was maintained on anti-TNF therapy for the initial 6 months in a total of 106 patients (77%), who were included in the study after anti-TNF therapy was stopped. By 8 months, 39 of 106 (37%) patients experienced disease flare after stopping anti-TNF therapy. The mean time to flare was 212 days. The investigators found that 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 had significantly lower hazard ratios (P <.05) for likelihood of flare by 8 months.

Limitations of the study included the small population size, potential selection bias for patients with more severe disease as a result of the study’s recruitment from an academic setting, and the failure to determine the difficulty of regaining clinically inactive disease among those who had a flare.

The authors note that the data do not support a protective effect of longer duration of clinically inactive disease before cessation of anti-TNF therapy. They also note that for each month less of disease duration prior to initiating aggressive therapy, the likelihood of reaching clinically inactive disease was increased by 1.7-fold. In contrast, longer duration of disease prior to first achieving clinically inactive disease was significantly associated with a decreased ability to maintain clinically inactive disease after stopping anti-TNF therapy.

Reference

Lovell DJ, Johnson AL, Huang B, et al. Risk, timing, and predictors of disease flare after discontinuation of anti-tumor necrosis factor (TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) in clinical inactive disease [published online March 31, 2018]. Arthritis Rheumatol. doi: 10.1002/art.40509