Etanercept treatment for extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or psoriatic arthritis

To describe the 6-year safety and efficacy of etanercept (ETN) in children with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA) METHODS: Patients who completed the 2-year, open-label, phase III CLinical Study In Pediatric Patients of Etanercept for Treatment of ERA, PsA, and Extended Oligoarthritis (CLIPPER) were allowed to enroll in its 8-year long-term extension (CLIPPER2). Children received ETN at a once-weekly dose of 0.8 mg/kg, up to a maximum dose of 50 mg/week. Efficacy assessments included the JIA core set of outcomes, the JIA American College of Rheumatology response criteria (JIA-ACR), and the Juvenile Arthritis Disease Activity Score (JADAS). Efficacy data are reported as responder analyses using a hybrid method for missing data imputation and as observed cases. Safety assessments included treatment-emergent adverse events (TEAEs).Out of 127 patients originally enrolled in CLIPPER, 109 (86%) entered CLIPPER2. After 6 years of trial participation (2 years in CLIPPER and 4 years in CLIPPER2), 41 (32%) patients were still taking ETN, 13 (11%) entered the treatment withdrawal phase after achieving low/inactive disease (of whom 7 had to restart ETN), 36 (28%) discontinued treatment for other reasons but are still being observed, and 37 (29%) discontinued treatment permanently. According to the hybrid imputation analysis, proportions of patients achieving JIA ACR90, JIA ACR100, and JADAS inactive disease after the initial 2 years of treatment were 58%, 48%, and 32%, respectively. After the additional 4 years, those proportions in patients who remained in the trial were 46%, 35%, and 24%. Most frequently reported TEAEs [n (%), events per 100 patient-years] were headache [28 (22%), 5.3], arthralgia [24 (19%), 4.6], and pyrexia [20 (16%), 3.8]. Number and frequency of TEAEs, excluding infections and injection site reactions, decreased over the 6-year period from 193 and 173.8, respectively, during year 1 to 37 and 61.3 during year 6. A single case of malignancy (Hodgkin's lymphoma) and no cases of active tuberculosis, demyelinating disorders, or deaths were reported.Open-label etanercept treatment for up to 6 years was safe, well tolerated, and effective in patients with eoJIA, ERA, and PsA.ClinicalTrials.gov: CLIPPER, NCT00962741 , registered 20 August, 2009, CLIPPER2, NCT01421069 , registered 22 August, 2011

Ability of the childhood health assessment questionnaire in predicting outcome of patients with juvenile idiopathic arthritis

Introduction. Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease associated with decreased functional capacity and potentially long-term consequences. The establishment of early prognostic factors could help in the prevention of joint damage and improve the quality of life in children with JIA. Objective. The aim of the study was to evaluate the functional status of children with JIA by using the Childhood Health Assessment Questionnaire (CHAQ) and to assess its ability in predicting the outcome of the disease. Methods. The study included 87 patients, average age 14 years, under follow-up on the average of 3.7 years. Parents/ patients over 12 years completed CHAQ based on which disability index (DI) was calculated. Disease outcome was determined according to the preliminary criteria for clinical remission. Results. At the end of the follow-up period, functional ability improved significantly (0.541 vs. 0.398; p<0.05). During the study, in 52.8% of patients treatment with biologic drug etanercept was introduced. CHAQ showed good predictive validity when a baseline DI was compared with disease outcome at the final examination (F=18.349; p<0.001). Using the patients with normal functional ability (DI=0) as the reference group, in patients with moderate and more severe functional disability the odds ratio for the disease to be active at the end of the follow-up period (DI≥0.6) was 4.6 (p=0.044). Conclusion. Functional ability of patients with JIA significantly improved during the follow-up period owing to the efficient therapy. The questionnaire for the assessment of the functional status is a simple tool, with good ability to predict disease outcome, and should thus be used in everyday clinical practice with the aim to identify patients with poor prognosis

Bone mineral density in patients with juvenile idiopathic arthritis

Introduction. It is well known that juvenile idiopathic arthritis (JIA) as a chronic inflammatory disease with onset during the childhood, beside other complication, can lead to bone metabolism disturbance and osteoporosis. Objective. To assess bone mineral density (BMD) in children with JIA and to identify factors playing role in bone mineral disturbance. Methods. Seventy-five patients (26 male and 49 female) average disease duration 7.2 (2.4-16.8) years, and 73 age matched healthy control subjects (29 male and 44 female) participated in the study. Mean age of the groups was about 14.5 years. BMD was determined by dual x-ray absorptiometry (DEXA) of the lumbar spine (L2-L4). For further analysis we used the absolute value of BMD, expressed as g/cm2, Z score expressed as SD (relative value as standard deviation decline of normal BMD values of referent Italian population with identical age and gender), bone mineral content (BMC) as g/cm, and corrected BMD - BMDv as g/cm3. Results. Z score in the group of patients was significantly lower (-1.02±1.6) in comparison to the control group (-0.09±1.4; p<0.001). BMD, BMDv and BMC were also statistically lower in patients with JIA. The lowest Z score was found in patients with systemic onset (-2.63 SD). Z score showed a statistically significant positive correlation with arthritis course (polyarticular course had lower Z score), body mass index and standard deviation score for height and weight. Statistically significant negative correlation was detected in regard to Z score and glucocorticoid (GC) treatment duration, GC cumulative dose, number of joints with limited range of motion, radiological stage and functional class. Conclusion. The results showed a decreased BMD in patients with JIA in comparison to the control group. Systemic onset, polyarthritis, longer treatment with GC and higher cumulative dosage, as well as higher damage level (functional status and radiological stage) are factors playing negative role in bone metabolism in children with JIA

Bone mineral density in children with juvenile idiopathic arthritis after one year of treatment with etanercept

Introduction/Objective. Juvenile idiopathic arthritis (JIA) is the most frequent chronic inflammatory, rheumatic disease of childhood, associated with disturbance of bone mineral metabolism, which develops gradually and progressively, and if untreated eventually leads to osteoporosis in adulthood. The aim of our study was to evaluate bone mineral density (BMD) in patients with JIA treated with etanercept over a period of one year. Methods. The prospective cohort study included 94 JIA patients (66 female, 28 male), their median age being 14.77 years. BMD was measured by dual-energy X-ray absorptiometry on the lumbar spine. Disease activity was assessed using the American College of Rheumatology Pedi 50 criteria. Results. After one year of treatment with etanercept, we found a statistically significant increment in all osteodensitometry variables (p < 0.001). Annual enhancement for the whole group was as follows: bone mineral content 15.8%, BMD 7.2%, BMDvol 4.2%. Z-score improved from -0.86 to -0.58 SD at the last visit, but decreased in rheumatoid factor-positive polyarthritis patients. Patients with systemic JIA had the lowest Z-score. Z-score correlated with functional disability level. BMD was lower in the group treated with glucocorticoids. Conclusion. Our results showed significant improvement of bone mineral density in children with JIA after one year of treatment with etanercept. Rheumatoid factor-positive and systemic JIA subtypes and treatment with glucocorticoids are the risk factors for impairing bone mineral metabolism