17 research outputs found
Advances in the Management of Juvenile Idiopathic Arthritis
__Abstract__
The main aim of this thesis was the evaluation of advances in the management of JIA. It
focused on developments in the biologic treatment of JIA, using data from the ABC register.
Additionally, it explored new biomarkers and methods for monitoring the disease activity,
bone age and bone health of patients with JIA
Significant pain decrease in children with non-systemic Juvenile Idiopathic Arthritis treated to target:results over 24 months of follow up
Background: The aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain. Methods: In the BeSt-for-Kids-study 92 DMARD-naïve JIA-patients were randomized in 3 treatment-strategies: 1) initial sequential DMARD-monotherapy 2) initial methotrexate (MTX)/prednisolone-bridging or 3) initial MTX/etanercept. Potential differences in VAS pain scores (0-100 mm) over time between treatment-strategies were compared using linear mixed models with visits clustered within patients. A multivariable model was used to assess the ability of baseline characteristics to predict the chance of high pain-scores during follow-up. Results: Pain-scores over time reduced from mean 55.3 (SD 21.7) to 19.5 (SD 25.3) mm after 24 months. On average, pain-scores decreased significantly with β -1.37 mm (95% CI -1.726; -1.022) per month. No significant difference was found between treatment-strategies (interaction term treatment arm*time (months) β (95% CI) arm 1: 0.13 (-0.36; 0.62) and arm 2: 0.37 (-0.12; 0.86) compared to arm 3). Correction for sex and symptom duration yielded similar results. Several baseline characteristics were predictive for pain over time. Higher VAS pain [β 0.44 (95% CI 0.25; 0.65)] and higher active joint count [0.77 (0.19; 1.34)] were predictive of higher pain over time, whereas, low VAS physician [-0.34 (-0.55; -0.06)], CHQ Physical [-0.42 (-0.72; -0.11)] and Psychosocial summary Score [-0.42 (-0.77; -0.06)] were predictive of lower pain. Conclusions: Treatment-to-target seems effective in pain-reduction in non-systemic JIA-patients irrespective of initial treatment-strategy. Several baseline-predictors for pain over time were found, which could help to identify patients with a high risk for development of chronic pain. Trial registration: Dutch Trial Registry number 1574.</p
A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis: Challenges and opportunities
Background: To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration. Methods: We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies. We captured information about study design, duration, location, inclusion criteria, data elements and collection methods. Results: We received survey results from 18 studies, including 11 national and 7 multi-national studies representing 37 countries in total. Study designs included inception cohorts, prevalent disease cohorts, and new treatment cohorts (several of which contribute to pharmacosurveillance activities). Despite numerous differences, the data elements collected across the studies was quite similar, with most studies collecting at least 5 of the 6 American College of Rheumatology core set variables and the data needed to calculate the 3-variable clinical juvenile disease activity score. Most studies were collecting medication initiation and discontinuation dates and were attempting to capture serious adverse events. Conclusion: There is a wide-range of large, ongoing JIA registries and cohort studies around the world. Our survey results indicate significant potential for future collaborative work using data from different studies and both combined and comparative analyses
Efficacy of biological agents in juvenile idiopathic arthritis: A systematic review using indirect comparisons
Objective Over the past decade, the availability of
biological agents for the treatment of juvenile idiopathic
arthritis ( JIA) has increased substantially. Because direct
head-to-head trials comparing these agents are lacking,
we indirectly compared their efficacy.
Methods In a systematic review, all available efficacy
data from randomised controlled trials performed in
JIA with inclusion of biological agents were retrieved.
Indirect between-drug comparisons (based on Bucher’s
method) were conducted only if trials were comparable
with regard to design and patients’ characteristics
related to treatment outcome.
Results We identified 11 randomised controlled trials.
On the basis of the equality of the trials, six trials were
grouped into two networks of evidence. Network 1
included withdrawal trials which evaluated etanercept,
adalimumab and abatacept in polyarticular course JIA.
Indirect comparisons identified no significant differences
in short-term efficacy. Network 2 indirectly compared
trials with a parallel study design investigating anakinra,
tocilizumab and canakinumab in systemic JIA; no
differences in comparative efficacy were identified.
Although the two networks were constructed on the
basis of comparability, small differences in trial design
and case mix still existed.
Conclusions Because of the small number of trials and
the observed differences between trials, no definite
conclusions could be drawn about the comparative
effectiveness of the indirectly compared biological
agents. Therefore, for now, the paediatric rheumatologist
has to rely on observational data and safety, practical
and financial arguments. Comparability of future trials
needs to be improved, and head-to-head trials are
required to decide on the best biological treatment
for JIA
Bone health of patients with juvenile idiopathic arthritis: a comparison between dual-energy X-ray absorptiometry and digital X-ray radiogrammetry
Juvenile idiopathic arthritis (JIA) affects bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) is the most widely used technique to determine BMD. Digital X-ray radiogrammetry (DXR) is a feasible method for determination of cortical BMD on hand radiographs. This study aimed to compare DXR and DXA in the assessment of BMD in JIA patients. Thirty-five JIA patients with available DXA and hand radiograph within the same time period were included from the Dutch Arthritis and Biologicals in Children register. Outcome measures for BMD were Bone Health Index from DXR and BMD total body, BMD lumbar spine and Bone Mineral Apparent Density from DXA. All measures were transformed to Z-scores. Correlations were assessed with Pearson correlation coefficients. Median age of the patients (60% female) was 11.7 years. Pearson correlation coefficient was significant for the absolute scores: 0.568-0.770 (p <0.001). No significant correlation was found between the Z-scores of DXA and DXR. The BMD assessment from the DXR was correlated to DXA measures in a cohort of JIA patients, although only in absolute scores. Future steps for implementation of DXR in clinical practice include evaluation of responsiveness to change, predictive value and comparison with other imaging technique
Concise report Long-term quality of life and functional outcome of patients with juvenile idiopathic arthritis in the biologic era: a longitudinal follow-up study in the Dutch Arthritis and Biologicals in Children Register
Abstract Objective. To carry out a longitudinal investigation of functional outcome, health-related quality of life (HRQoL) and treatment strategies in JIA patients who started etanercept >5 years ago. Methods. We approached patients whose HRQoL changes were described previously in a subanalysis of the Dutch Arthritis and Biologicals in Children register. Recent disease status, co-morbidities and structural damage were retrieved. Disability and HRQoL were assessed by (Childhood) HAQ [(C)HAQ], Child Health Questionnaire, Short Form 36 and Health Utilities Index Mark 3. Changes over time were analysed with linear mixed models
Long-term quality of life and functional outcome of patients with juvenile idiopathic arthritis in the biologic era: a longitudinal follow-up study in the Dutch Arthritis and Biologicals in Children Register
To carry out a longitudinal investigation of functional outcome, health-related quality of life (HRQoL) and treatment strategies in JIA patients who started etanercept >5 years ago. We approached patients whose HRQoL changes were described previously in a subanalysis of the Dutch Arthritis and Biologicals in Children register. Recent disease status, co-morbidities and structural damage were retrieved. Disability and HRQoL were assessed by (Childhood) HAQ [(C)HAQ], Child Health Questionnaire, Short Form 36 and Health Utilities Index Mark 3. Changes over time were analysed with linear mixed models. Forty-three patients (81% response) started etanercept a median 8.5 years ago. At the time of this long-term analysis, median age was 22 years (interquartile range: 18-24 years). HRQoL outcome was similar to HRQoL 15-27 months after the initiation of etanercept; 42% had a (C)HAQ of 0.00 and 67% had achieved inactive disease. Patients reported increasing levels of bodily pain compared with earlier measurements. Unemployment (12%) was comparable to the general population; educational level was higher. Use of biologic agents was as follows: 40% etanercept; 40% other biologic agents; and 20% none. Joint surgery occurred in 14% of patients. At a median 8.5 years after the commencement of etanercept treatment, JIA patients maintain most of the acquired improvement in HRQoL. Although disability and disease activity are low, chronic pain remains an issue. Persistence and possible deterioration of radiological damage emphasize the importance of early treatment. The fact that 20% of patients do not use any anti-rheumatic medication shows that clinical remission of medication might be an achievable goa
S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis
Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response. S100A12 serum concentration was determined by ELISA in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and followup. Treatment response (≥ ACRpedi50 score), achievement of inactive disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10 score were recorded. Baseline S100A12 concentration was measured in patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200, interquartile range (IQR) 133-440 ng/ml] and MTX (median 220, IQR 100-440 ng/ml). Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX. Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125-615) ng/ml versus 150 (IQR 87-233) ng/ml, p = 0.021 for MTX, and median 308 (IQR 150-624) ng/ml versus 151 (IQR 83-201) ng/ml, p = 0.002, for anti-TNF therapy. Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44 responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p < 0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and multivariate regression models for anti-TNF therapy and univariate analysis alone for MTX therapy was significantly associated with change in JADAS-10. Responders to MTX or anti-TNF treatment can be identified by higher pretreatment S100A12 serum concentration level