Conversely, prior research found flare rates in patients with JIA treated with MTX to be more closely related to S100 levels than those in patients treated with biologic DMARDs (e.g. TNF inhibitors) [32]; additionally, high baseline S100A12 levels were found to predict improvement with MTX or TNF inhibitor therapy in patients with pJIA, with a decrease in S100A12 levels observed with treatment over time [21]. This evidence concerns the gene S100A12 and juvenile idiopathic arthritis.