title: Uveitis Events During Adalimumab, Etanercept, and Methotrexate Therapy in Juvenile Idiopathic Arthritis: Data From the Biologics in Pediatric Rheumatology Registry.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hamburger Zentrum für Kinder und Jugendrheumatologie, Hamburg, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Foeldvari
authors.affiliation: Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Cologne, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Becker
authors.affiliation: Asklepios Clinic Sankt Augustin, Centre of Pediatric Rheumatology, Sankt Augustin, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Horneff
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D001688:Biological Products / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D000068800:Etanercept / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D012042:Registries; D012219:Rheumatology / Q000379:methods; D013223:Statistics as Topic / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014605:Uveitis / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate