Biomarker Changes in Response to Tofacitinib Treatment in Patients with Polyarticular Course Juvenile Idiopathic Arthritis.

Abstract

Examine levels of candidate blood-based biomarkers (CBB) in juvenile idiopathic arthritis (JIA) treated with tofacitinib. JIA patients who participated in clinical trial NCT02592434 received tofacitinib from baseline to week 18. Serial serum samples were assayed for CBB (S100A8/9, S100A12, IL-18, SAA, resistin, VEGF, Angiopoietin-1, Angiopoietin-2, MMP8, MMP2, TIMP1, Leptin, CXCL9, sIL2R, ICAM-1, sTNFr, IL-6, IL-23, MCP1, CCL18, and CCL20). Association of CBB with JIA response to treatment from baseline to week 18 were assessed. This study included 166 patients with polyarticular-course JIA. Paired serum samples from 143 patients were available at both baseline and week 18. There were 35% (50/143) of patients with a JIA-American College of Rheumatology 90 (JIA-ACR90) level improvement while 90/121/137 (63%/85%/96%) achieved JIA-ACR70/50/30 improvement at wk18. Despite small numerical differences by JIA category, there were no baseline CBB values that independently predicted a decrease in JADAS-27 or JIA-ACR90 response by week 18. Decrease in resistin level (baseline to week 18) was significantly associated with wk18 improvement in JADAS-27 and JIA-ACR90 response, after adjusting for age, sex, JIA disease duration and baseline resistin [(r2 0.79, SE, 0.070, p<0.01 and OR(95%CI) = 1.134(1.018,1.264)]. HLA-B27 positivity was significantly associated with not achieving a JIA-ACR90 response at week 18 (p=0.0097). Among the CBB included, only resistin was significantly associated with treatment response, and no CBB was identified that forecasts JIA improvement after initiation of tofacitinib. The association of HLA-B27 positivity with lower response to tofacitinib in JIA is intriguing and merits further study.