Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry.

OBJECTIVE: Uveitis is a major extraarticular quality of life-restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX).

METHODS: Patients' characteristics, treatment, and the reported first occurrence of uveitis as an adverse event were searched in the Biologics in Pediatric Rheumatology Registry. The rates per exposed patients, exposure time, and time until event were calculated.

RESULTS: Uveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844 patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and 13 of 364 patients were receiving adalimumab. Patients with uveitis were younger (mean ± SD age 4.6 ± 4.2 versus 7.4 ± 4.5 years; P < 0.0001), more likely to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P < 0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with a uveitis diagnosis before starting treatment more often had a uveitis event (n = 28, 8.4%; OR 8.5, P < 0.0001), and more often received adalimumab (OR 2.15 [95% confidence interval 1.58-2.94], P < 0.0001). In 16 patients, a new uveitis event occurred: 11 while taking MTX (3.2 per 1,000 patient-years), 2 while taking etanercept monotherapy (1.9 per 1,000 patient-years), and 3 while taking etanercept and MTX combination (0.9 per 1,000 patient-years). A new uveitis event occurred early in the disease course after a median disease duration of 1.5 years (interquartile range [IQR] 1.3-3.8) while taking etanercept and 1.8 years (IQR 1.8-2.1) for the MTX cohort. A recurrent uveitis event was reported after a disease duration of 7.6 years (IQR 4.3-10.0) in the etanercept cohort and 4.8 years (IQR 1.0-5.8) in the MTX cohort. Univariate analysis showed that MTX, but not etanercept or adalimumab, led to a lower rate of uveitis.

CONCLUSION: Patients with a history of uveitis had higher risks for uveitis events while taking both etanercept and adalimumab. Methotrexate turned out to be protective. Few patients developed a first uveitis event while taking etanercept, while the rate is comparable to that with MTX. Uveitis may not be attributed to be an adverse drug reaction to etanercept.