Prevalence of vertebral compression fractures and associated factors in children and adolescents with severe juvenile idiopathic arthritis.

OBJECTIVE: Vertebral fractures occur in patients with juvenile idiopathic arthritis (JIA), but data on their frequency and causes are scarce. Our cross-sectional study evaluated prevalence of compression fractures and associated factors in a high-risk pediatric population with severe JIA. METHODS: Children and adolescents with a history of treatment-resistant polyarticular-course JIA for ≥ 5 years or systemic arthritis for ≥ 3 years were recruited. Clinical examination, dietary recall, laboratory measurements, bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry, and spinal radiography were performed. RESULTS: Our study included 50 patients (41 girls), of whom 6 (12%) had systemic arthritis, with a median age of 14.8 years (range 7.0-18.7 yrs) and median disease duration of 10.2 years (range 3.9-16.8 years). Ninety-four percent had used systemic glucocorticoids (GC); the median total duration of GC treatment was 7.1 years (range 0-15.5 yrs). The median weight-adjusted cumulative GC dose for the preceding 3 years was 72 mg/kg (range 0-911 mg/kg). The median bone age-corrected lumbar spine and whole-body areal BMD Z-scores were -0.8 and -1.0, respectively. Twenty-two percent had vertebral fractures, mostly thoracic. Compression fractures were associated with high disease activity, high body mass index (BMI), and high recent cumulative GC dose, but not with disease duration or BMD. Thirty percent had sustained at least 1 peripheral low energy fracture. Twenty-six percent were deemed to have significantly compromised bone health. CONCLUSION: Severe JIA is associated with a significant risk of vertebral compression fractures. Associated factors include high disease activity, high BMI, and high recent GC exposure. Further studies are needed to establish optimal prevention and treatment guidelines.

Aggressive combination drug therapy in very early polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label clinical trial.

OBJECTIVES: In juvenile idiopathic arthritis (JIA), the efficacy of very early disease-modifying drug therapy, synthetic or biological, is not well known. Three alternative strategies were compared for treating recent-onset polyarticular JIA. METHODS: In a 54-week multicentre open-label clinical trial, 60 disease-modifying antirheumatic drug (DMARD)-naive patients aged 4-15 years were randomly assigned into three treatment arms. The efficacy of infliximab plus methotrexate (TNF) was compared to that of two synthetic therapies: methotrexate alone (MTX) and DMARD methotrexate, sulphasalazine and hydroxychloroquine in combination (COMBO). Primary endpoint was American College of Rheumatology paediatric 75% improvement (ACR Pedi 75). Secondary endpoints were inactive disease and safety. RESULTS: In 59 patients, mean (±SE) age at baseline was 9.6±0.4 years, duration of JIA 1.9±0.2 months and number of active joints 18±1. ACR Pedi 75 was achieved in 100% (19/19) of patients receiving TNF, 65% (13/20) on COMBO (95% CI 44% to 86%) and 50% (10/20) on methotrexate (95% CI 28% to 72%) p<0.0001. Thirteen patients receiving TNF (68%; 95% CI 47% to 89%) achieved inactive disease, whereas eight (40%; 95% CI 22% to 63%) on COMBO and five (25%; 95% CI 6% to 44%) on methotrexate did (p=0.002). Patients on TNF spent a mean 26 weeks (95% CI 18 to 34) with inactive disease, longer than did those receiving COMBO (13 weeks; 95% CI 6 to 20), or methotrexate (6 weeks; 95% CI 2 to 10). Serious adverse events were rare. CONCLUSION: In early polyarticular JIA, targeting to achieve minimally active or inactive disease, infliximab plus methotrexate was superior to synthetic DMARD in combination and strikingly superior to methotrexate alone.

Iron status during anti-TNF therapy in children with juvenile idiopathic arthritis.

Patients with active juvenile idiopathic arthritis (JIA) have frequently low haemoglobin (Hgb) due to inflammation and/or iron deficiency. The aim of the study was to evaluate the effect of anti-tumor necrosis factor (TNF) therapy on their iron status. Twenty children with JIA were treated with either etanercept (n = 8) or infliximab (n = 12) for 12 months. Iron status was assessed during anti-TNF treatment by Hgb, mean corpuscular volume of red blood cells (MCV), serum iron (sFe), ferritin, percent transferrin saturation (sTrfesat) and serum transferrin receptor concentration (sTfR). The sTfR/log ferritin index (TfR/logF) was also used. Prior to the therapy, Hgb and MCV were 118 ± 15.5 g/L and 79 ± 7.7 fl in the infliximab group, and 113 ± 12.5 g/L and 78 ± 5.8 fl in the etanercept group, respectively. In the whole group of patients, sFe was 6.3 ± 4.1 µmol/L and sTrfesat was 9% ± 6%. During anti-TNF therapy, Hgb and MCV improved significantly without use of iron supplementation, and sFe and sTrfesat increased from low to normal levels while inflammation markers decreased, except in one patient, in whom sTfR stayed elevated and the TfR/logF index value was high. In patients with active JIA associated with anaemia, low levels of sFe and sTrfesat cannot be used as markers for iron deficiency. In such patients, sTfR together with TfR/logF seem to be useful in assessing iron deficiency.

Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis.

OBJECTIVE: To evaluate the efficacy of anti-tumour necrosis factor (anti-TNF) treatment in juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: 24 patients with uveitis taking etanercept and 21 taking infliximab were studied. The endpoint ophthalmological evaluation was at 24 months or at the termination of the first biological agent. The ocular inflammatory activity was graded on the basis of the number of anterior chamber cells. RESULTS: Of the 45 patients, uveitis improved in 14 (31%), no change was observed in 14 (31%) and the activity of uveitis increased in 17 (38%). Inflammatory activity improved more frequently (p=0.047) in the patients taking infliximab than in those taking etanercept. The number of uveitis flares/year was higher (p=0.015) in the patients taking etanercept (mean 1.4, range 0-3.2) than in those taking infliximab (mean 0.7, range 0-2). Uveitis developed for the first time while taking anti-TNF treatment in five patients-4 taking etanercept (2.2/100 patient-years) and 1 taking infliximab (1.1/100 patient-years). CONCLUSIONS: During anti-TNF treatment, the ophthalmological condition improved in one-third of the patients with uveitis. In chronic anterior uveitis, associated with refractory JIA, infliximab may be more effective than etanercept.