Search

Objective The clinical decision-making process in paediatric arthritis lacks an objective, reliable bedside imaging tool. The aim of this study was to develop a US scanning protocol and assess the reliability of B-mode and Doppler scoring systems for inflammatory lesions of the paediatric ankle. Methods As part of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) US group, 19 paediatric rheumatologists through a comprehensive literature review developed a set of standardized views and scoring systems to assess inflammatory lesions of the synovial recesses as well as tendons of the paediatric ankle. Three rounds of scoring of still images were followed by one practical exercise. Agreement among raters was assessed using two-way single score intraclass correlation coefficients (ICC). Results Of the 37 initially identified views to assess the presence of ankle synovitis and tenosynovitis, nine views were chosen for each B-mode and Doppler mode semi-quantitative evaluation. Several scoring exercises and iterative modifications resulted in a final highly reliable scoring system: anterior tibiotalar joint ICC: 0.93 (95% CI 0.92, 0.94), talonavicular joint ICC: 0.86 (95% CI 0.81, 0.90), subtalar joint ICC: 0.91 (95% CI 0.88, 0.93) and tendons ICC: 0.96 (95% CI 0.95, 0.97). Conclusion A comprehensive and reliable paediatric ankle US scanning protocol and scoring system for the assessment of synovitis and tenosynovitis were successfully developed. Further validation of this scoring system may allow its use as an outcome measure for both clinical and research applications. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to develop and validate a brief disability screen for children with JIA, the Kids Disability Screen (KDS). Methods A total of 216 children enrolled in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry in 2017–2018 formed a development cohort, and 220 children enrolled in 2019–2020 formed a validation cohort. At every clinic visit, parents answered two questions derived from the Childhood Health Assessment Questionnaire (CHAQ): 'Is it hard for your child to run and play BECAUSE OF ARTHRITIS?' ('Hard' 0–10), and 'Does your child usually need help from you or another person BECAUSE OF ARTHRITIS?' ('Help', 0–10). We used 36-fold cross-validation and tested nine different mathematical methods to combine the answers and optimize psychometric properties. The results were confirmed in the validation cohort. Results Expressed as the mean of the two answers, KDS best balanced ease of use and psychometric properties, while a LASSO regression model combining the two answers with other patient characteristics [estimated CHAQ [eCHAQ]) had the highest responsiveness. In the validation cohort, 22.7%, 25.9% and 28.6% of patients had a score of 0 at enrolment for the KDS, eCHAQ and CHAQ, respectively. Responsiveness was 0.67, 0.74 and 0.62, respectively. Sensitivity to detect a CHAQ > 0 was 0.90 and specificity 0.56, KDS detecting some disability in 44% of children with a CHAQ = 0. Conclusion This simple KDS has psychometric properties comparable with those of a full CHAQ and may be used at every clinic visit to identify those children who need a full disability assessment. [ABSTRACT FROM AUTHOR]

Objectives Differential diagnosis in children with prolonged fever is challenging. In particular, differentiating systemic-onset JIA (SJIA) from infectious diseases is difficult. Biomarkers are needed that support the diagnostic work-up. The aim of this study was to validate the usefulness of Myeloid-related protein 8/14 (MRP8/14) measurements in the diagnostic work-up of febrile children and to transfer it to clinical practice. Methods Data for 1110 paediatric patients were included and divided into two cohorts: (cohort A) for validation of MRP8/14 test performance with three different testing systems: the experimental ELISA, commercial ELISA and an innovative (point-of-care test) lateral flow immunoassay (LFIA); (cohort B) to validate the diagnostic accuracy with the two latter assays. Results In cohort A (n  = 940), MRP8/14 was elevated in SJIA (12 110 ± 2650 ng/ml mean ± 95% CI) compared with other diagnoses (including infections and autoinflammatory diseases; 2980 ± 510 ng/ml) irrespective of fever and anti-inflammatory treatment (P  < 0.001). In untreated patients with fever (n  = 195) MRP8/14 levels in SJIA (19 740 ± 5080 ng/ml) were even higher compared with other diagnoses (4590 ± 1160 ng/ml) (P  < 0.001, sensitivity 73%, specificity 90%). In group B1, the performance of the tests was confirmed in untreated patients with fever (n  = 170): commercial ELISA (sensitivity 79%, specificity 89%) and LFIA (sensitivity 84%, specificity 81%). Compared with ferritin, IL-18, ESR, soluble IL-2 receptor and procalcitonin, MRP8/14 showed the best accuracy. Conclusion MRP8/14 serum analyses have been validated as a helpful tool supporting the diagnosis of SJIA in febrile children. The results could be confirmed with commercial ELISA and LFIA enabling a rapid diagnostic point-of-care screening test. [ABSTRACT FROM AUTHOR]

Objectives To determine s.c. tocilizumab (s.c.-TCZ) dosing regimens for systemic JIA (sJIA) and polyarticular JIA (pJIA). Methods In two 52-week phase 1 b trials, s.c.-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or <30 kg, respectively. Primary end points were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with i.v. tocilizumab (i.v.-TCZ) in sJIA and pJIA. Results Study participants were 51 sJIA patients and 52 pJIA patients aged 1–17 years who received s.c.-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with i.v.-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis DAS-71 were comparable between s.c.-TCZ and i.v.-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of i.v.-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered to be related to TCZ. Conclusion s.c.-TCZ provides exposure and risk/benefit profiles similar to those of i.v.-TCZ. S.c. administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov , NCT01904292 and NCT01904279 [ABSTRACT FROM AUTHOR]

Background: With an incidence of 1 in 1000, juvenile idiopathic arthritis (JIA) is one of the most common paediatric rheumatological disorders. The number of children who fail to respond to the standard therapy methotrexate (MTX) is about 30%. Predicting which patients will respond to MTX at time of disease diagnosis is therefore clinically important. MRP8/14 is an inflammatory protein: low levels are associated with lower risk of JIA disease flare after MTX withdrawal (Foell D, et. al. 2010). Here we present data on the levels of MRP8/14 in the SPARKS CHARMS JIA cohort to investigate if this might be a predictor of response to MTX.Methods: The SPARKS CHARMS study enrols patients with all subtypes of JIA (ILAR criteria) being treated with MTX for their arthritis and collects samples and clinical data at 0 and 6 months of treatment. In this part of the study 113 patients were available for analysis. The study had full ethical approval. Serum was collected and processed within 3 hours of collection from the patient. Serum concentrations of MRP8/14 were determined by an in-house sandwich ELISA as previously reported (Foell D, et. al. 2004). The analysing laboratory was blinded for patients’ characteristics. MRP8/14 concentrations are presented as mean ± s.d. in ng/ml.Results: Concentration of MRP8/14 was measured in serum from JIA patients in the CHARMS cohort, at 0 and 6 months of treatment with MTX. Patients were stratified by disease type according to ILAR criteria: patients with systemic JIA (sJIA) had higher MRP8/14 levels pre-treatment compared with other subtypes, (34,283 ± 41182 ng/ml in sJIA patients compared to 3,838 ± 3443 ng/ml in polyarticular RF-JIA). Interestingly levels of MRP8/14 pre-MTX in patients who would go on to a good response (ACR70) to MTX, were higher than levels of MRP8/14 in those who would not respond (NR). Importantly, the percentage of sJIA patients in the ACR70 group was comparable at 10.2% compared to 7.1% in NR. When systemic patients were excluded from this analysis a higher level of MRP8/14 was still observed in patients from the ACR70 group versus NR (3,016 ± 3189 ng/ml, 1,658 ± 917 ng/ml, respectively).Conclusions: Here we show that serum MRP8/14 levels are increased in JIA patients who will go on to respond well to MTX treatment. Measurement of MRP8/14 is not currently routine, but notably MRP8/14 is a robust protein and serum samples can be sent for diagnostic testing without cold storage. Therefore we conclude that this inflammatory marker may be a useful adjunct to predict which patients are more likely to go onto respond to MTX therapy at time of diagnosis. [ABSTRACT FROM PUBLISHER]