Juvenile Idiopathic Arthritis Patients Research Articles

Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial

BackgroundEtanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial.Methods92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week.Results32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4–10), median 10 months (7–16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6–9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group.ConclusionsEscalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety.Trial registrationDutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585.

Adherence to low-dose methotrexate in children with juvenile idiopathic arthritis using a sensitive methotrexate assay

BackgroundLow-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined.MethodsThis was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy.ResultsPlasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher’s Exact).ConclusionsQuantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy.

Challenges Nurses Face in Providing Care for Patients with Juvenile Idiopathic Arthritis

Abstract Objectives: This study aimed at identifying challenges nurses face in caring for patients with juvenile idiopathic arthritis (JIA) in Japan. Methods: Nurses certified by the Japan Rheumatism Foundation were asked to describe their challenges with caring for JIA patients. Data was analyzed using qualitative content analysis. Results: Responses were collected from 89 participants. 58 issues were identified from 40 participants with experience caring for JIA patients. Sixteen categories emerged, grouped into five challenges: communication, understanding, expertise, system, and collaboration. Care for JIA patients included different challenges from adult patients with rheumatoid arthritis, such as complicated patient-parent relationships, inadequate patient independence and insufficient patient information. Moreover, 76 issues from 49 participants with no experience were identified. Seven categories emerged, grouped into two challenges: expertise and opportunity. Issues included in expertise between both groups were similar. Even with no experience caring for JIA patients, nurses recognized the importance of acquiring knowledge. Conclusion: This is the first study in Japan regarding the difficulties nurses face in caring for JIA patients. Multidisciplinary team care and a comprehensive understanding of the patient journey, including relationships with guardians, acquaintances, and healthcare providers, is crucial to improve treatment outcome and overall patient quality of life.

Comparative efficacy and safety of different drugs in patients with systemic juvenile idiopathic arthritis: A systematic review and network meta-analysis.

The goal of this study was to estimate the relative efficacy and safety of different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) compared with placebo for systemic juvenile idiopathic arthritis (JIA) patients, through a network meta-analysis. Pubmed, Embase, and Cochrane Library were searched from database inception to July 2023 for randomized controlled trials comparing different biological agents (infliximab, canakinumab, baricitinib, anakinra, adalimumab, tofacitinib, tocilizumab, and rilonacept) or placebo directly or indirectly in JIA. Bayesian network meta-analyses were conducted. Data was extracted and analyzed by R with gemtc package. The treatment options were ranked using the surface under the cumulative ranking curve (SUCRA) value. We identified 10 randomized controlled trials and analyzed 898 participants. Canakinumab (odds ratio 55.0, 95% credible intervals 2.4-67.0) was more effective than the placebo, and the difference was statistically significant. However, there was no statistical significance between other drugs versus placebo in terms of the modified ACRpedi30 (P > .05). The SUCRA shows that canakinumab ranked first (SUCRA, 86.9%), anakinra ranked second (SUCRA, 77.7%), adalimumab ranked third (SUCRA, 61.9%), and placebo ranked the last (SUCRA, 6.3%). Nevertheless, there were no notable discrepancies in the occurrence of adverse events, hepatic-related adverse events, infectious adverse event, serious adverse events, and serious infection following treatment with canakinumab, anakinra, tocilizumab, rilonacept, or the placebo. Based on the clustergram of modified ACRpedi30 and adverse events, canakinumab is suggested for JIA according to the surface under SUCRAs considering the symptom and adverse events simultaneously. Among patients with JIA, canakinumab exhibited the highest likelihood of being the optimal treatment for achieving the modified ACRpedi30 response rate, and neither of the tested biological agents carried a significant risk of serious adverse events.

Relapses of juvenile idiopathic arthritis in adulthood: A monocentric experience.

Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care. We conducted a retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression. Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse. In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.

Comprehensive analysis of juvenile idiopathic arthritis patients' immune characteristics based on bulk and single-cell sequencing data.

The pathogenesis of juvenile idiopathic arthritis (JIA) is strongly influenced by an impaired immune system. However, the molecular mechanisms underlying its development and progression have not been elucidated. In this study, the computational methods TRUST4 were used to construct a T-cell receptor (TCR) and B-cell receptor (BCR) repertoire from the peripheral blood of JIA patients via bulk RNA-seq data, after which the clonality and diversity of the immune repertoire were analyzed. Our findings revealed significant differences in the frequency of clonotypes between the JIA and healthy control groups in terms of the TCR and BCR repertoires. This work identified specific V genes and J genes in TCRs and BCRs that could be used to expand our understanding of JIA. After single-cell RNA analysis, the relative percentages of CD14 monocytes were significantly greater in the JIA group. Cell-cell communication analysis revealed the significant role of the MIF signaling pathway in JIA. In conclusion, this work describes the immune features of both the TCR and BCR repertoires under JIA conditions and provides novel insight into immunotherapy for JIA.

Factors determining resistance to conventional disease-modifying anti-rheumatic drug treatment in oligoarticular juvenile idiopathic arthritis.

Our study was designed to investigate the reasons for starting the conventional disease-modifying anti-rheumatic drugs (DMARDs) and the variables that impact the response to DMARD treatment in oligoarticular juvenile idiopathic arthritis (JIA) patients. Oligoarticular JIA patients (n = 187) were categorized into two groups: Group A consisted of patients who achieved remission with DMARD, and Group B comprised those who did not respond to DMARD therapy. DMARDs were initiated for various reasons: 68 (36.4%) due to active disease despite nonsteroidal anti-inflammatory drugs (± intra-articular corticosteroid) treatment, 59 (31.6%) due to uveitis, 49 (26.2%) due to extended oligoarticular JIA, and 11 (5.9%) due to inflammatory bowel disease. One hundred twenty-three patients (65.8%) achieved remission with DMARDs (Group A), while 64 patients (34.2%) did not respond to DMARD therapy (Group B). In Group B, patients had higher C-reactive protein (CRP) levels as well as higher Juvenile Idiopathic Arthritis Disease Activity Scores-71 (JADAS-71) at diagnosis (both p < 0.001). Moreover, extended oligoarticular JIA subtype (p = 0.017) and involvement of small joints at diagnosis (p = 0.043) were more prevalent among these patients. Group A exhibited a higher frequency of antinuclear antibody positivity (p = 0.014). Elevated CRP levels (> 1.1mg/dL) (OR 1.308, 95% CI 1.203-3.574; p < 0.001) and high JADAS-71 at diagnosis (> 15.8) (OR 1.659, 95% CI 1.179-2.941; p < 0.001) were associated with DMARD resistance. Elevated CRP and high JADAS-71 at diagnosis were the main factors associated with DMARD resistance in oligoarticular JIA. Prospective long-term studies may help verify the role of these factors associated with DMARD resistance in oligoarticular JIA. Key Points • Conventional DMARDs were most commonly started due to active disease despite NSAID (± intra-articular corticosteroids). • Remission was achieved with DMARD in 65.8% of oligoarticular JIA patients. • Elevated CRP and high JADAS-71 at diagnosis were associated with DMARD resistance.

Caregiver burden in families of children with juvenile idiopathic arthritis in India.

Juvenile Idiopathic Arthritis (JIA) causes caregiver burden on families with children affected with it. Our study aimed to explore this multifaceted burden in the Indian context. In this cross-sectional study, we administered the Hindi translated CAREGIVER questionnaire to adult caregivers in the families of JIA patients ≤ 18years. The responses to the 28 items were used to calculate the burden scores in various dimensions. The relationship of the global burden scores with demographic and socioeconomic factors were analysed. Non parametric tests were used. Two hundred twenty-one caregivers participated with a median age of 39years (IQR 32-45). This included 116 fathers, 50 mothers, 32 brothers, 18 uncles, three grandfathers, one sister, and one grandmother. The JIA patients had a median age of 15 (12-17) years, and the male-to-female ratio was 3.2:1. Enthesitis-related arthritis was the predominant subtype (72.4%). Most caregivers (70.6%) expressed sadness at diagnosis, and 29.9% continued to express sadness. Nearly two-thirds (65.6%) had to borrow money from others. More than half (59.3%) of the caregivers neglected their health, and 9.0% became sick. Male gender of the child, systemic JIA subtype, low socioeconomic status, high disease activity, extra-articular damage, high parent-reported disease activity and poor quality of life were associated with higher global caregiver burden. JIA has a significant emotional, social, economic, and labour impact on caregivers. Economic and psychosocial support needs to be given to family caregivers caring for children with JIA.

P088 Uveitis screening in Juvenile Idiopathic Arthritis: Are we following the guidelines?

Abstract Background/Aims Juvenile Idiopathic Arthritis (JIA) is the most common inflammatory arthritis in children. Uveitis is a common (8-30%) and potentially sight-threatening complication of JIA. Early detection and treatment of uveitis can prevent permanent visual impairment, making uveitis screening an essential part of the management of JIA patients. The purpose of this audit was to evaluate the referral and management of uveitis screening in JIA patients in our healthcare setting compared with Guidelines for Screening for Uveitis in Juvenile Idiopathic Arthritis (JIA) produced jointly by BSPAR and the RCOphth 2006. Methods The patients with a diagnosis of JIA at our District General Hospital (DGH) were reviewed retrospectively. The data was collected based on demographics, JIA diagnosis, subtypes, referral for uveitis screening, timing of uveitis screening, and screening outcome. Data was then analysed to assess if we met BSPAR and the RCOphth 2006 standards. Results A total of 42 patients were identified with a diagnosis of JIA between January 2021 and January 2023. Based on our criteria, four patients were excluded and the final analysis was done with 38 patients. 34 patients (89%) with JIA were referred for uveitis screening. 31 of those patients (91%) were referred within six weeks, while three patients (9%) were referred after six weeks of diagnosis. Only nine patients (24%) were seen for uveitis screening within the six weeks after initial referral as per BSPAR and the RCOphth 2006 standards. Uveitis was diagnosed in five patients(13%). One out of 38(2.6%) patients was diagnosed with Uveitis prior to diagnosis of JIA. Regarding the distribution of JIA subtypes, there were 15 cases of Polyarticular JIA, 14 instances of Oligoarticular JIA, six occurrences of Psoriatic JIA, two instances of Enthesitis-related JIA, and 1 case of Systemic JIA. Out of the five patients diagnosed with Uveitis, two had Polyarticular JIA, two had Oligoarticular JIA, and one presented with Psoriatic JIA. Furthermore, two of these patients tested positive for ANA, one tested negative, while the ANA status remained unknown for the remaining two individuals. Conclusion The results showed the need for improvement to be fully compliant with the guidelines for screening uveitis in JIA patients. We aim to ensure that all patients are referred and reviewed within 6 weeks for uveitis screening, as early detection and treatment of uveitis can prevent permanent visual impairment. We recommend collaborating with the ophthalmology unit to streamline the referral pathway and explore the idea of doing MDT clinics. Education should be arranged to raise awareness among all relevant healthcare staff. Disclosure J. Ahmad: None. A. Gupta: None. A. Bharadwaj: None. D. Olusanya: None.

P098 Anti-adalimumab antibodies are associated with active Juvenile Idiopathic Arthritis

Abstract Background/Aims Biologics have been used widely in the UK to treat Juvenile Idiopathic Arthritis (JIA) for over two decades. As this population has aged and switched biologics, there has been a growth in the cohort of patients who have switched through a greater number of biologics, consequently having fewer therapeutic options available. Our group has recently published data suggesting adalimumab has a greater drug survival compared to etanercept and infliximab. As part of our further investigation, we examined the relationship between adalimumab antibodies (AAA) and drug levels, stratified by disease activity (remission vs. active disease). Methods We conducted a retrospective observational study among patients with JIA and measured adalimumab drug levels and AAAs. The key metrics measured were AAAs (AU/L) and adalimumab drug levels (mg/mL). Disease remission was determined using standard Wallace criteria.The differences between the active and remission groups were examined with the Mann-Whitney U test. Results Among our cohort of 293 JIA patients receiving adalimumab, 179 had recorded adalimumab levels and AAAs. In 146 of these patients, we were able to measure disease activity, which was stratified into two distinct categories: Remission (N = 96) and Active (N = 50) according to Wallace criteria. Within our cohort of patients, there was a significant difference in both adalimumab drug levels, (P = 0.004) and AAAs (P = 0.00009) among those with active disease when compared to those in remission. Specifically, those with active disease exhibited a higher geometric mean AAA of 156.89 AU/L [95% CIs (95% confidence intervals) 129.65-189.85] when compared to those in remission with a mean of 65.25 AU/L (95% CI 41.10-103.58). The median AAA levels in those with active disease was 91 AU/L (IQR 0-200), compared with 0 (IQR 0-12.5) among those in remission. With respect to adalimumab drug levels, the geometric mean in patients with active disease was 7.27 mg/mL (95% CI 5.15-10.26) compared with 8.55 mg/mL (95% CI 7.26, 10.07) for patients in remission. The median drug level in the active group was 2.3 mg/ml (IQR 0-11.9) when compared with 9.4 mg/ml (IQR 3.8-13.1) in the remission group. Conclusion Various studies have demonstrated that the presence of AAAs is associated with secondary failure in JIA and other rheumatic diseases. However, the precise relationship between AAAs, adalimumab drug concentration and disease activity are yet to be elucidated, thus their regular monitoring is not currently part of guidelines or routine clinical practice.To our knowledge this is the largest single-centered cross-sectional study investigating the relationship of AAAs and remission state in JIA.Our study demonstrates that not only are higher AAAs associated with lower drug concentration, but that this is further associated with active disease. Disclosure M.W. Carrim: None. D. Sen: None. M. Shipa: None. C. Fisher: None. T. AlSulaim: None. A. Bouraoui: None. M. Leandro: None. C. Ciurtin: None. J. Glanville: None.

Measuring synovial thickness on knee MRI in pediatric patients with arthritis: is contrast necessary?

The use of contrast-enhanced imaging has long been standard for magnetic resonance imaging (MRI) assessments of synovitis in juvenile idiopathic arthritis (JIA). However, advancements in MRI technology have allowed for reliable identification of synovium without contrast. To assess the equivalence of unenhanced MRI with contrast-enhanced MRI in evaluating synovial thickness. This is an institutional review board approved, retrospective study performed in a tertiary children's hospital. Pediatric JIA patients under 21 years old were included who underwent knee MRI scans (1.5 T or 3 T) without and with contrast between January 2012 and January 2022. Two radiologists independently measured synovial thickness at 6 knee sites on contrast-enhanced and unenhanced sequences. Numerical measurements and ordinal scores based on juvenile idiopathic arthritis magnetic resonance imaging scoring (JAMRIS) system were recorded, and tests of equivalence were conducted, as well as between-reader and within-reader reliability by concordance correlation coefficient (CCC). All tests were considered significant at the 5% level. A total of 38 studies from 35 patients (25 females, median age 14 years; interquartile range 7 to 15.7) were included. Equivalence was demonstrated at each of the 6 sites for both continuous measurements (P-values < 0.05) and ordinal scores (P-values < 0.05) based on the average over readers. Within-reader reliability was moderate to high (CCC 0.50-0.89), except for the cruciate ligaments site. Averaged over the 6 sites, reliability between readers was low for unenhanced (CCC 0.47, with 95% CI: [0.41, 0.53]) and moderate for contrast-enhanced (CCC 0.64, with 95% CI: [0.59, 0.69]) sequences. Unenhanced knee MRI is equivalent to contrast-enhanced MRI in assessment of synovial thickness using conventional MRI sequences. Contrast material helped improve inter-reader reliability.

The Juvenile Arthritis Quality of Life Questionnaire in patients with juvenile idiopathic arthritis: Turkish version, validity, and reliability study.

This study aimed to assess the cultural adaptation, validity, and reliability of the Turkish version of the Juvenile Arthritis Quality of Life Questionnaire (JAQQ) in patients with juvenile idiopathic arthritis (JIA). A total of 100 JIA patients (64% female), aged 9 to 18years, participated in the study conducted at a tertiary care university hospital. The JAQQ was culturally adapted through a rigorous translation process and administered alongside established measures, including the Childhood Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Biopsychosocial Questionnaire (JABQ), and Children's Depression Inventory (CDI). Validity and reliability were evaluated using Spearman's correlation coefficients, Cronbach's alpha, intraclass correlation coefficient (ICC), standard error of the mean (SEM), and minimal detectable change (MDC). The Turkish version of JAQQ exhibited high convergent validity, correlating significantly with CHAQ, JABQ, and CDI. No floor or ceiling effects were observed in the total JAQQ score, indicating a balanced assessment. Internal consistency was excellent (Cronbach's α = 0.948), and test-retest reliability was satisfactory (ICC = 0.913). SEM and MDC95 values were 0.357 and 0.99, respectively. The Turkish adaptation of JAQQ emerges as a valid and reliable instrument for comprehensively assessing the health-related quality of life in children and adolescents diagnosed with JIA. The questionnaire's robust psychometric properties, coupled with distinctive features like individualized assessment, highlight its potential as a valuable tool for both clinical assessment and scientific research in the field of pediatric rheumatology. Key Points • The Juvenile Arthritis Quality of Life Questionnaire (JAQQ) is an important scale that evaluates the quality of life of children with Juvenile Idiopathic Arthritis (JIA). • JAQQ is known and used in the field of pediatric rheumatology in Turkey, but its Turkish adaptation has not been made before. • Our study includes 100 JIA patients aged between 9 and 18 years and shows that the Turkish version of JAQQ is valid and reliable in measuring the quality of life of these children. • This research contributes to the accurate assessment of the quality of life in Turkish children diagnosed with JIA, providing valuable insights for both clinical and scientific studies.

Does sacroiliitis is a mandatory criterion for enthesitis-related arthritis diagnosis?

Magnetic resonance imaging (MRI) sensitivity and specificity seem to be less studied in enthesitis-related arthritis (ERA). We aimed to determine the ability of sacroiliac MRI to diagnose ERA patients. We conducted a retrospective study including 44 patients with juvenile idiopathic arthritis (JIA). Each patient had a sacroiliac joint MRI. We divided patients into two groups: G1 patients with ERA and G2 patients with non-ERA subtype. ERA was noted in 61% of the cases. Sacroiliac joints were painful in 15 patients (34%). MRI was normal in 25 patients (57%) (G1:11 versus G2:14) and showed bone marrow edema in the sacroiliac joints in 19 patients (34%) (G1=16 versus G2=3, p=0.005). Sacroiliac joints MRI's sensitivity and specificity in the ERA diagnosis were 61.54% and 82.35%, respectively. Positive and negative predictive values were 84.21% and 58.33%, respectively. Furthermore, sacroiliac joint pain in the clinical examination was able to predict sacroiliac bone edema in MRI with an odds ratio of 6.8 (95% CI 1.68-28.09; p=0.006). Our study showed that sacroiliac joint MRI has good specificity and positive predictive value in the diagnosis of ERA patients among JIA patients. This underlines the usefulness of sacroiliac joint MRI in the early diagnosis of ERA patients.

When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?

JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs. • Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections. • Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies. • Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up. • The JADAS10 calculated at 3 and 6months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA.

Level and correlates of physical activity among children and adolescents with juvenile idiopathic arthritis compared to controls: results from a German nationwide prospective observational cohort study

BackgroundPhysical active lifestyles are essential throughout growth and maturation and may offer potential preventive and therapeutic benefit in patients with juvenile idiopathic arthritis (JIA). Insufficient physical activity (PA), in contrast, can lead to aggravation of disease-related symptoms. This study aimed to i) examine PA levels in children and adolescents with JIA compared to general population controls and ii) investigate correlates of pronounced physical inactivity in order to identify risk groups for sedentary behaviour.MethodsData from children and adolescents with JIA and population controls aged 3 to 17 years documented in the National Pediatric Rheumatologic Database (NPRD) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were used. Self-reported PA was collected from parents/guardians of children up to 11 years of age or adolescents 12 years of age and older. To compare PA-related data, age- and sex-specific pairwise analyses were conducted considering NPRD/KiGGS participants' data from 2017. Correlates of physical inactivity among patients were identified using a linear regression model.ResultsData of 6,297 matched-pairs (mean age 11.2 ± 4.2 years, female 67%, patients’ disease duration 4.5 ± 3.7 years, persistent oligoarthritis 43%) were available for evaluation. Almost 36% of patients aged 3–17 years (vs. 20% of controls) achieved the WHO recommended amount of PA, while PA steadily decreased with age (18% of patients aged ≥ 12 years) and varied between JIA categories. Female adolescents and patients with enthesitis-related arthritis were least likely to achieve the minimum recommended level of PA. Physical inactivity was associated with female sex, higher age at disease onset, longer disease duration, more functional disability (C-HAQ) and higher disease activity (cJADAS-10).ConclusionsDepending on JIA category, children and adolescents with JIA were similarly or even more likely to achieve the WHO recommended minimum level of PA compared to general population controls. However, since a large proportion of young JIA patients appear to be insufficiently physically active, engagement in targeted efforts to promote PA is urgently needed.

Assessment of Bone Mineral Density in a cohort of Juvenile Idiopathic Arthritis patients

Introduction: Low bone mass is encountered in patients with Juvenile idiopathic arthritis (JIA) as a serious long-term complication of this pediatric condition and may be associated with fractures and its complications.&#x0D; The present study aimed to evaluate the frequency of low bone mineral density (BMD) and fragility fractures in patients with JIA in its polyarticular or oligo articular forms. Secondary, our aim was to identify factors associated with low bone mass.&#x0D; Patients and methods: This is a retrospective study conducted on 26 patients with JIA meeting the ILAR criteria for poly or oligoarticular form. Patients were divided into two groups according to their age : group1 including patients aged over 16 years-old and group 2 including patients aged under 16 years-old. Sociodemographic, clinical, biological and functional data were collected by consulting patient’s medical records. Bone mineral density was measured at three different sites: whole body, lumbar spine and hip using the dual-energy X-ray absorptiometry (DXA) equipment. Data were entered and analyzed using SPSS version 11.5 software.&#x0D; Results: Twenty-six JIA patients including 20 females (74.1%) and six males (22.2%) were enrolled with a mean disease duration of 20.23 years [2-54 years]. The mean age was 28.2 years [7-58 years]. The distribution of JIA subtypes among patients was as follows: 6 with oligo articular JIA and 20 with polyarticular JIA. Sixteen patients (59%) practiced regular physical activity. In our series, the frequency of low bone mineral density was 41% in children with JIA and 68 % in adults with JIA. Only two patients presented a fragility fracture in adulthood represented by a hip fracture following low-energy trauma and treated surgically in both cases. No patient received an anti-osteoporotic treatment. In-group 1, there was a significant correlation between low bone mass and weight (p=0.020), BMI (p=0.028), disease duration (p=0.045), positivity of AAN (p=0.050), disease activity (p=0.019), oral corticosteroid (p=0.034) and biologic treatment (p=0.043). In-group 2, a statistically significant correlation was found between low bone mass and age at the time of JIA diagnosis (p=0.041), weight (p=0.03), physical activity (p=0.05), disease duration (p=0.021), functional impact of the disease assessed by the HAQ score (p=0.018), oral corticosteroid therapy (p=0.014) and biological therapy (p=0.012).&#x0D; Conclusion: our study showed that a combination of factors contributed to compromise bone health in patients with JIA. Fragility fractures were rare and occurring mainly in adulthood. An adequate control of disease activity, proper management of treatment, adequate calcium and vitamin D intake, as well as regular physical activity, may contribute to preserve bone health in those patients.

Tumor-necrosis factor α-rich environment alters type-I interferon response to viral stimuli in patients with juvenile idiopathic arthritis by altering myeloid dendritic cell phenotype

The balance between the tumor-necrosis factor α (TNFα) and type-I interferon (T1IFN) pathways is crucial for proper immune function. Dysregulation of either pathway can contribute to autoimmune diseases development. Even though TNFα blockade has shown promising results in various autoimmune diseases, the effect on the balance between TNFα and T1IFN is elusive. We used targeted anti-TNFα therapies in juvenile idiopathic arthritis (JIA) as an experimental approach to study the cross-regulation between TNFα and type-I IFN. We found that TNFα-rich environment affected viral defense through the attenuation of T1IFN responses and affected the phenotype and distribution of myeloid dendritic cells, which are engaged in early viral infections. Anti-TNFα therapy normalized the observed deviations in JIA patients. We hypothesize that the inadequate immune response caused by a high TNFα environment could be projected to more frequent or lengthy viral infections and possibly play a role in the process of JIA disease development.

Construction and validation of a machine learning model for the diagnosis of juvenile idiopathic arthritis based on fecal microbiota.

Human gut microbiota has been shown to be significantly associated with various inflammatory diseases. Therefore, this study aimed to develop an excellent auxiliary tool for the diagnosis of juvenile idiopathic arthritis (JIA) based on fecal microbial biomarkers. The fecal metagenomic sequencing data associated with JIA were extracted from NCBI, and the sequencing data were transformed into the relative abundance of microorganisms by professional data cleaning (KneadData, Trimmomatic and Bowtie2) and comparison software (Kraken2 and Bracken). After that, the fecal microbes with high abundance were extracted for subsequent analysis. The extracted fecal microbes were further screened by least absolute shrinkage and selection operator (LASSO) regression, and the selected fecal microbe biomarkers were used for model training. In this study, we constructed six different machine learning (ML) models, and then selected the best model for constructing a JIA diagnostic tool by comparing the performance of the models based on a combined consideration of area under receiver operating characteristic curve (AUC), accuracy, specificity, F1 score, calibration curves and clinical decision curves. In addition, to further explain the model, Permutation Importance analysis and Shapley Additive Explanations (SHAP) were performed to understand the contribution of each biomarker in the prediction process. A total of 231 individuals were included in this study, including 203 JIA patients and Non-JIA individuals. In the analysis of diversity at the genus level, the alpha diversity represented by Shannon value was not significantly different between the two groups, while the belt diversity was slightly different. After selection by LASSO regression, 10 fecal microbe biomarkers were selected for model training. By comparing six different models, the XGB model showed the best performance, which average AUC, accuracy and F1 score were 0.976, 0.914 and 0.952, respectively, thus being used to construct the final JIA diagnosis model. A JIA diagnosis model based on XGB algorithm was constructed with excellent performance, which may assist physicians in early detection of JIA patients and improve the prognosis of JIA patients.

Anti-tumor necrosis factor (aTNF) weaning strategy in juvenile idiopathic arthritis (JIA): does duration matter?

To compare outcomes of a short and long weaning strategy of anti-tumor necrosis factor (aTNF) in our prospective juvenile idiopathic arthritis (JIA) cohort. JIA patients on subcutaneous adalimumab with at least 6months of follow-up were recruited (May 2010-Jan 2022). Once clinical remission on medication (CRM) was achieved, adalimumab was weaned according to two protocols-short (every 4-weekly for 6months and stopped) and long (extending dosing interval by 2weeks for three cycles until 12-weekly intervals and thereafter stopped) protocols. Outcomes assessed were flare rates, time to flare, and predictors. Of 110 JIA patients, 77 (83% male, 78% Chinese; 82% enthesitis-related arthritis) underwent aTNF weaning with 53% on short and 47% on long weaning protocol. The total flare rate during and after stopping aTNF was not different between the two groups. The time to flare after stopping aTNF was not different (p = 0.639). Positive anti-nuclear antibody increased flare risk during weaning in long weaning group (OR 7.0, 95%CI: 1.2-40.8). Positive HLA-B27 (OR 6.5, 95%CI: 1.1-30.4) increased flare risks after stopping aTNF. Duration of weaning aTNF may not minimize flare rate or delay time to flare after stopping treatment in JIA patients. Recapture rates for inactive disease at 6months remained high for patients who flared after weaning or discontinuing medication.

Frosted branch angiitis in a patient with systemic juvenile idiopathic arthritis: a case report

BackgroundFrosted branch angiitis is a retinal vascular condition that is associated with a viral infection or autoimmune disorders like Crohn’s disease, systemic lupus erythematosus, and Behcet’s disease. Frosted branch angiitis presents with vascular inflammation, retinal edema, and severe retinal vascular sheathing. We present a case of systemic juvenile idiopathic arthritis, an autoinflammatory disease, presenting with frosted branch angiitis.Report of CaseA 14-year-old female with systemic juvenile idiopathic arthritis and a history of bilateral anterior uveitis developed acute unilateral vision loss and was found to have frosted branch angiitis complicated by branch retinal vein occlusion. She underwent an extensive serology workup and aqueous viral PCR to rule out other possible autoimmune and viral etiologies for forested branch angiitis. She received systemic and intravitreal antiviral treatment due to positive CMV IgM initially. However, the clinical picture improved following the use of a higher dose of oral steroids and the switch of the immunosuppressive agent to a TNF-a inhibitor.ConclusionTo our knowledge, this would be the first case in the literature demonstrating a systemic juvenile idiopathic arthritis patient presenting with frosted branch angiitis. Infectious causes still must be ruled out, especially CMV, as it is the most common cause of secondary frosted branch angiitis.