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Introduction: The aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE).Methods: We ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observ

OBJECTIVE: To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE). METHODS: One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models. RESULTS: Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score. CONCLUSION: Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhood-onset SLE disease activity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate changes in brain activation patterns detected by functional magnetic resonance imaging (FMRI), and the relationship between FMRI activation patterns and results of formal neuropsychological testing, in patients with childhood-onset systemic lupus erythematosus (SLE). METHODS: Ten patients with childhood-onset SLE underwent formal neuropsychological testing and FMRI using 3 paradigms: a continuous performance task (CPT) to evaluate attention, an N-Back task to assess working memory, and verb generation to evaluate language processing. Composite Z maps were generated to summarize the brain activation patterns for each FMRI paradigm in patients with childhood-onset SLE and to compare these patterns with those observed in healthy controls. Between-group comparison Z maps showing differences in activation between childhood-onset SLE patients and controls were generated, using a significance level of P < 0.05 in a general linear model. RESULTS: Compared with the control group, the childhood-onset SLE group showed statistically significant increased activation of brain areas involved in the CPT, N-Back, and verb generation tasks. In contrast, in the absence of active stimulus, e.g., during times of the paradigm control tasks, childhood-onset SLE patients consistently undersuppressed activity in the expected brain areas. Activation in selected cortical areas was found to correlate negatively with results of a subset of individual neuropsychological test scores. CONCLUSION: FMRI abnormalities are present in childhood-onset SLE, manifesting as an imbalance between active and inhibitory responses to an array of stimuli. Differences in brain activation patterns compared with those observed in controls suggest that childhood-onset SLE may be associated with abnormalities in white matter connectivity resulting in neuronal network dysfunction, rather than injury of specific gray matter areas. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Macrophage activation syndrome is characterized by an overwhelming inflammatory reaction driven by excessive expansion of T cells and hemophagocytic macrophages. Levels of soluble interleukin-2 receptor alpha (sIL-2Ralpha) and soluble CD163 (sCD163) may reflect the degree of activation and expansion of T cells and macrophages, respectively. This study was undertaken to assess the value of serum sIL-2Ralpha and sCD163 in diagnosing acute macrophage activation syndrome complicating systemic juvenile idiopathic arthritis (JIA). METHODS: Enzyme-linked immunosorbent assay was used to assess sIL-2Ralpha and sCD163 levels in sera from 7 patients with acute macrophage activation syndrome complicating systemic JIA and 16 patients with untreated new-onset systemic JIA. The results were correlated with clinical features of established macrophage activation syndrome, including ferritin levels. RESULTS: The median level of sIL-2Ralpha in the patients with macrophage activation syndrome was 19,646 pg/ml (interquartile range [IQR] 18,128), compared with 3,787 pg/ml (IQR 3,762) in patients with systemic JIA (P = 0.003). Similarly, the median level of sCD163 in patients with macrophage activation syndrome was 23,000 ng/ml (IQR 14,191), compared with 5,480 ng/ml (IQR 2,635) in patients with systemic JIA (P = 0.017). In 5 of 16 patients with systemic JIA, serum levels of sIL-2Ralpha or sCD163 were comparable with those in patients with acute macrophage activation syndrome. These patients had high inflammatory activity associated with a trend toward lower hemoglobin levels (P = 0.11), lower platelet counts, and significantly higher ferritin levels (P = 0.02). Two of these 5 patients developed overt macrophage activation syndrome several months later. CONCLUSION: Levels of sIL-2Ralpha and sCD163 are promising diagnostic markers for macrophage activation syndrome. They may also help identify patients with subclinical macrophage activation syndrome. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Renal involvement in systemic lupus erythematosus (SLE) is associated with poor prognosis. Currently available renal biomarkers are relatively insensitive and nonspecific for diagnosing SLE nephritis. Previous research suggests that neutrophil gelatinase-associated lipocalin (NGAL) is a high-quality renal biomarker of acute kidney injury, while its usefulness in SLE is unclear. We undertook this study to determine the relationship between urinary NGAL excretion and SLE disease activity or damage, with a focus on nephritis. METHODS: A cohort of 35 patients diagnosed as having SLE prior to age 16 years (childhood-onset SLE) was assessed for disease activity (using the Systemic Lupus Erythematosus Disease Activity Index 2000 update) and damage (using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLE Damage Index) in a double-blind, cross-sectional study. Information on current markers of renal function and disease was obtained and compared with NGAL levels (ng/mg of urinary creatinine) measured by enzyme-linked immunosorbent assay. Eight children with juvenile idiopathic arthritis (JIA) served as controls. RESULTS: NGAL levels did not differ with the age, weight, height, sex, or race of the patients. Patients with childhood-onset SLE had significantly higher NGAL levels than did those with JIA (P < 0.0001). NGAL levels were strongly to moderately correlated with renal disease activity and renal damage (Spearman's r >/= 0.47, P < 0.0001 for both comparisons), but not with extrarenal disease activity or extrarenal damage. NGAL levels of >0.6 ng/mg urinary creatinine were 90% sensitive and 100% specific for identifying childhood-onset SLE patients with biopsy-proven nephritis. CONCLUSION: Urinary NGAL is a promising potential biomarker of childhood-onset SLE nephritis. The results of the current study require validation in a larger cohort to more accurately delineate urinary NGAL excretion in relation to the diverse SLE phenotypes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the relationship between the vasculopathy of juvenile dermatomyositis (juvenile DM) and the balance between the angiostatic ELR- and angiogenic ELR+ CXC chemokines in the muscle of patients with the disease. METHODS: The expression of 3 ELR- CXC chemokines (interferon-inducible protein 10 [IP-10], monokine induced by interferon-gamma, and interferon-inducible T cell alpha-chemoattractant) and 2 ELR+ CXC chemokines was quantitated in muscle biopsy samples from 7 patients with juvenile DM and 7 healthy children, by real-time polymerase chain reaction. The findings were correlated with various histopathologic features, with particular emphasis on the degree of vasculopathy. Synovial biopsy specimens from patients with juvenile rheumatoid arthritis (JRA) were used for additional comparison. RESULTS: The angiostatic ELR- chemokines were expressed at high levels, while the angiogenic ELR+ chemokines were barely detectable, in most juvenile DM samples. This contrasted sharply with the findings in both normal muscle biopsy specimens and JRA synovial tissue specimens. The expression of the ELR- chemokines in juvenile DM samples correlated with the intensity of mononuclear cell infiltration. Furthermore, the juvenile DM samples with the highest degree of capillary loss had the highest levels of ELR- CXC chemokines. The presence of IP-10 in juvenile DM muscle specimens was confirmed by immunohistochemistry analysis. In addition, immunohistochemical staining of muscle tissue revealed that CXCR3, a receptor utilized by ELR- CXC chemokines, was expressed in vascular endothelial cells. CONCLUSION: Increased expression of the interferon-induced angiostatic ELR- CXC chemokines is a feature of juvenile DM that parallels the degree of vasculopathy in patients with the disease. Collectively, these findings are consistent with a model in which a subset of inflammatory cells secrete angiostatic ligands, which then contribute to a local atrophying effect on the muscle's vasculature via a receptor-mediated process. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To use a core set of outcome measures to develop preliminary definitions of improvement for adult and juvenile myositis as composite end points for therapeutic trials. METHODS: Twenty-nine experts in the assessment of myositis achieved consensus on 102 adult and 102 juvenile paper patient profiles as clinically improved or not improved. Two hundred twenty-seven candidate definitions of improvement were developed using the experts' consensus ratings as a gold standard and their judgment of clinically meaningful change in the core set of measures. Seventeen additional candidate definitions of improvement were developed from classification and regression tree analysis, a data-mining decision tree tool analysis. Six candidate definitions specifying percentage change or raw change in the core set of measures were developed using logistic regression analysis. Adult and pediatric working groups ranked the 13 top-performing candidate definitions for face validity, clinical sensibility, and ease of use, in which the sensitivity and specificity were >/=75% in adult, pediatric, and combined data sets. Nominal group technique was used to facilitate consensus formation. RESULTS: The definition of improvement (common to the adult and pediatric working groups) that ranked highest was 3 of any 6 of the core set measures improved by >/=20%, with no more than 2 worse by >/=25% (which could not include manual muscle testing to assess strength). Five and 4 additional preliminary definitions of improvement for adult and juvenile myositis, respectively, were also developed, with several definitions common to both groups. Participants also agreed to prospectively test 6 logistic regression definitions of improvement in clinical trials. CONCLUSION: Consensus preliminary definitions of improvement were developed for adult and juvenile myositis, and these incorporate clinically meaningful change in all myositis core set measures in a composite end point. These definitions require prospective validation, but they are now proposed for use as end points in all myositis trials. [ABSTRACT FROM AUTHOR]

The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is the most commonly used measure of disease activity for children with systemic lupus erythematosus(SLE). For headachesto be scored in the SLEDAI as a symptom of active disease, they have to be nonresponsive to narcotic analgesia. This may affect the overall estimation of disease activity, especially because headaches are common among children with SLE and narcotic analgesia is rarely used for headache therapy in paediatrics. Moreover, the importance of headaches for the development of damage and their relation to other clinical parameters and outcomes has not been well described for children with SLE. We reviewed the medical charts of an inception cohort of children (n = 63) who were newly diagnosed with SLE. Information on headaches and other disease parameters was obtained. Disease activity and damage were measured using the SLEDAI and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI), respectively. It has been shown that the accumulated burden of active disease as measured by serial SLEDAI scores over time is one of the best predictors of eventual damage to children with SLE. New-onset or significant increase of severe and/or persistent headaches (LHA) were reportedin 43% of the patients during a mean follow-up of 3.6 years. LHA occurred preferentiallyamong patients with elevated levels of antiphospholipid antibodies (aPL) (P < 0.02) and only 6% of all LHA episodes were treated with narcotics and thus considered for the measurement of disease activity in the SLEDAI. LHA were unrelated to proxy-measures of disease activity, such as the need to intensify therapies. When used in children, the insensitivity of the SLEDAI to capture LHA did not seem to decrease the responsiveness of the SLEDAI to detect clinically important worsening of disease, or negatively impact on its ability to predict damage. [ABSTRACT FROM AUTHOR]

BACKGROUND: Health-related quality of life can be measured by patients' health preferences (utilities or values). No method for measuring health state preferences has been standardized for children with arthritis or other musculoskeletal disorders (MSKDs). Such a method is needed for economic evaluations of current and new pediatric treatments. OBJECTIVES: 1) To assess the feasibility of utility measurements in children with MSKDs, 2) to test the validity of the Health Utility Index (HUI) for these children, 3) to assess whether rating scale values can be mathematically converted into meaningful standard gamble (SG) utilities, and 4) to study whether parents can act as proxies for their children with respect to health state preferences. METHODS: Eighty parents of children with MSKDs were consecutively sampled. Their children, if 8 years of age or older (n = 55), were studied concurrently. Utilities of current health states were obtained by using the SG and the HUI in random order. In addition, health state preferences were assessed using categorical and analog rating scales. Traditional nonutility measures of health status (the Childhood Health Assessment Questionnaire [CHAQ] and the Activities Scale for Kids [ASK]) were also completed. Intraclass correlation coefficients (ICCs) were calculated to assess concordance between the different utility measures and also between the ratings of the parents and their children. RESULTS: Children 8 years of age or older were able to express the strength of their health state preferences using the HUI and rating scales. Children older than 10 years of age were able to use the SG method. The health state utilities of the parents were higher than those of their children. The utilities varied widely depending on the elicitation method. The expected high agreement between the SG and the HUI was not found (ICC = 0.028 for parents, ICC = 0.016 for patients). Unlike the SG, the global utilities derived from the HUI agreed better with preferences derived from rating scales (ICC = 0.23-0.25) and correlated with traditional health status measures (with CHAQ, r = -0.56; with ASK, r = 0.46) both for parents and children. It was not possible to mathematically convert rating scale preferences into SG utilities. The SG utilities were unrelated to results from the rating scales, the CHAQ, and the ASK. Especially for parents, the SG utilities were very high, even when ratings of the other measures indicated poor health. CONCLUSIONS: Although it is possible to measure health utilities for children with MSKDs, the results are highly method dependent. The properties of the HUI in this population are more like those of the traditional health status measures rather than those of the SG. Preferences derived from rating scales, although easily performed, cannot readily be converted into SG utilities. Parents' ratings for their children are impaired by risk aversion. [ABSTRACT FROM AUTHOR]

Objectives: This work aimed to evaluate the pharmacokinetics, efficacy, and safety of upadacitinib, an oral selective JAK inhibitor, in pediatric patients with polyarticular-course juvenile idiopathic arthritis (pcJIA)., Methods: In an open-label, phase 1 study (SELECT-YOUTH), enrolled patients, aged 2 to <18 years with pcJIA, received bodyweight-based upadacitinib doses using a twice-daily (BID) oral solution or once-daily (QD) extended-release tablet based on their body weight and ability to swallow tablets. The study included a 7-day pharmacokinetic assessment, followed by a long-term efficacy and safety evaluation for up to 156 weeks, including an additional long-term safety cohort. This interim analysis included available pharmacokinetic and safety data and efficacy data collected through Week 48., Results: A total of 57 patients received upadacitinib. The median time to maximum upadacitinib concentration was approximately 3 hours and 1 hour for the tablet and oral solution regimens, respectively; the harmonic mean functional half-life was approximately 5 hours and 2 hours, respectively. Juvenile idiopathic arthritis (JIA) American College of Rheumatology (ACR)30/50/70/90/100 responses at Week 12 were 91.8/89.8/69.4/49.0/32.7%, respectively. Efficacy was generally maintained through Week 48, and improvement in additional efficacy endpoints was also observed. At a median exposure duration of 412 days, 52 of 57 patients reported adverse events, of these 6 experienced serious adverse events. Adverse events were predominately mild to moderate in severity and consistent with the known safety profile of upadacitinib., Conclusions: This interim analysis demonstrates that the bodyweight-based dosing regimen of upadacitinib was well tolerated and efficacious in pediatric patients with pcJIA., (This article is protected by copyright. All rights reserved.)

Objective: To investigate occupational and hobby exposures to silica, solvents, and heavy metals and odds of idiopathic inflammatory myositis (IIM) phenotypes, dermatomyositis (DM) and polymyositis (PM) versus inclusion body myositis (IBM), lung disease plus fever or arthritis (LD+), and systemic autoimmune rheumatic disease-overlap myositis (OM)., Methods: The sample included 1390 patients (598 DM, 409 PM, and 383 IBM) ages ≥18 years from a national registry. Of these, 218 (16%) were identified with LD+, i.e., self-reported lung disease with fever and/or arthritis, and 166 (12%) with OM. Questionnaire data on jobs, hobbies, and exposures before diagnosis were evaluated using a rules-based protocol and expert assessment of silica dust, solvents, and heavy metals exposure. We calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) and explored joint effects with smoking., Results: High silica exposure was associated with an increased odds of having DM (OR=2.02; 95%CI 1.18-3.46, compared to no exposure; p-trend=0.004), LD+ (1.75; 1.10-2.78; p-trend=0.005, versus no LD), and OM (2.07; 1.19-3.61; p-trend=0.020). Moderate to high heavy metals exposure was associated with greater odds of having LD+ (1.49; 1.00-2.14; p-trend=0.026) and OM (1.59; 0.99-2.55, p-trend=0.051). Greater odds of LD+ were seen among smokers with moderate to high silica exposure versus non-smokers with low or no exposure (high-certainty assessment, 2.53; 1.31-4.90; p-interaction=0.061)., Conclusion: These findings, based on a systematic exposure assessment, suggest that occupational and hobby exposures to silica and heavy metals contribute to adult IIM phenotypes, including DM, OM, and LD+, a possible marker for anti-synthetase or other autoantibody-associated lung disease., (This article is protected by copyright. All rights reserved.)

Objectives: To assess changes in gene expression following tofacitinib treatment and investigate transcription patterns as potential predictors of treatment response in patients with active juvenile idiopathic arthritis (JIA)., Methods: Whole blood samples were collected from JIA patients at baseline and after 18 weeks of open-label tofacitinib treatment (clinical trial NCT02592434). Patients who achieved a JIA-American College of Rheumatology (ACR) response of 70 or above at week 18 were classified as treatment-responders (TR) while those with at most a JIA-ACR30 response were classified as poor-responders (PR). Differential gene expression and gene ontology (GO) over-representation analyses were performed to compare RNA expression between week 18 and baseline samples, as well as between PR and TR samples at baseline., Results: Samples from 67 patients at baseline and 60 at week 18 were analyzed. Following 18 weeks of tofacitinib treatment across all JIA subjects, 883 genes showed significant differential expression (week 18 - baseline). The most strongly downregulated genes were over-represented within IL-7, type I, and type II interferon pathways, while upregulated genes were enriched in ontologies related to neuronal cell processes and cell signaling. Comparing PR and TR at baseline, 663 genes showed differential expression. Upregulated genes were over-represented within ontologies including activation of MAPK activity (p=9.40x10 -5 ), myeloid cell development (p=8.13 x10 -5 ), activation of GTPase activity (p=0.00015), and organelle transport along microtubules (p=0.00021)., Conclusions: Tofacitinib treatment in JIA downregulated genes in interferon and IL-7 signaling pathways regardless of effectiveness. Furthermore, baseline upregulation of MAPK signaling may predict poor response to tofacitinib treatment in JIA., (This article is protected by copyright. All rights reserved.)

Objective: To report pharmacokinetics (PK), immunogenicity, clinical effect, and safety of intravenous (IV) golimumab in children with active polyarticular-course juvenile idiopathic arthritis (pcJIA) who participated in A Study to Evaluate the Pharmacokinetics, Efficacy and Safety of Intravenous Golimumab in Pediatric Participants With Active Polyarticular Course Juvenile Idiopathic Arthritis Despite Methotrexate Therapy (GO-VIVA)'s open-label, long-term extension (LTE) through week 252., Methods: GO-VIVA participants who continued IV golimumab (80 mg/m 2 every 8 weeks) after week 52 were included. PK and safety were assessed through week 244 (last dose) and week 252, respectively, and clinical response through week 116. Clinical outcomes included JIA-American College of Rheumatology (ACR) responses and clinical Juvenile Arthritis Disease Activity Score in 10 joints (cJADAS10). Binary outcomes used nonresponder imputation, and other descriptive analyses used observed data., Results: Of 112/127 (88.2%) participants entering the LTE, 69 completed the week 252 visit. Median steady-state trough golimumab concentrations were generally maintained from week 52 through week 244 (range 0.3-0.6 μg/mL). Antigolimumab antibody rates were consistent through week 52 (39.2% [49/125]) and week 244 (44.8% [56/125]). Week 52 JIA-ACR 30/50/70/90 response rates (75.6% [96/127], 74% [94/127], 65.4% [83/127], and 48.8% [62/127], respectively) were generally maintained through week 116 (72.4% [92/127], 71.7% [91/127], 63.8% [81/127], and 50.4% [64/127], respectively), when the median cJADAS10 was 1.6 and 56.7% (72/127) of participants achieved cJADAS10 ≤ 5 (minimal disease activity). Rates (per 100 patient-years) of serious adverse events and serious infections through week 252 were 7.7 and 3.9, respectively., Conclusion: GO-VIVA LTE participants experienced adequate PK exposure and stable safety and immunogenicity. The majority of participants experienced no more than minimal residual disease activity. Data suggest IV golimumab treatment provided durable clinical response through week 116, with an acceptable risk-benefit profile., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: We compared the measurement properties of a traditional physician global assessment of disease activity (PhGA) 10-cm visual analog scale (PhGA 0-10 ) with that of the three-point numeric scale (PhGA 0-3 ) in childhood-onset systemic lupus erythematosus (cSLE) as part of the childhood Lupus Low Disease Activity State (cLLDAS)., Methods: We used a secondary data analysis from a convenience sample of 100 patients with cSLE followed every three months for up to seven visits. Ratings of PhGA 0-10 , PhGA 0-3 , parent assessment of patient well-being (ParGA) (range: 0= very poorly, 10 = very well), disease activity as measured by the SLE disease activity index 2000 (SLEDAI-2k), Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) SLEDAI, and the British Isles International Lupus Activity Group index (BILAG; A = 9, B = 3, C = 1, D/E = 0) were compared. After linear transformation of PhGA 0-10 to a 0 to 3 range (tPhGA 0-10 ), the frequency of PhGA 0-3 ≤1 was assessed to estimate the impact of scale type on the scoring of the cLLDAS., Results: In 600 visits, the median (range) scores of PhGA 0-10 , PhGA 0-3 , SLEDAI-2k, SELENA-SLEDAI, and BILAG were 2 (0-10), 1(0-3), 4 (0-28), 4 (0-32), and 2 (0-28), respectively. PhGA 0-10 and PhGA 0-3 ratings were strong to moderately correlated with (r = 0.73; P < 0.0001) and with more variability for PhGA 0-3 ≥2. SELENA-SLEDAI and SLEDAI-2k scores were moderately correlated with PhGA 0-10 (r = 0.56/0.54; P < 0.0001). ParGA values were weakly correlated with all other measures considered (all r = -0.19 to -0.34). There were 490 of 600 visits with PhGA 0-3 ≤1 and 497 of 600 visits with tPhGA 0-10 ≤1 (κ (SE) =0.59 (0.04), McNemar P = 0.4)., Conclusion: PhGA 0-3 and PhGA 0-10 have comparable measurement properties and yield almost identical cLLDAS rates when used in cSLE., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Despite availability of multiple FDA approved therapies, many children with juvenile idiopathic arthritis (JIA) suffer pain and disability due to uncontrolled disease. The term JIA includes a heterogeneous set of conditions unified by chronic inflammatory arthritis, collectively affecting 1:1,000 children. When reviewing treatment options with families the rheumatologist currently refers to the experience of the average patient in relatively small controlled clinical trials, to consensus-based treatment plans, or increasingly the choice is dictated by the formulary restrictions of insurance payers. The current paradigm for treatment selection does not incorporate real-world evidence of treatment effectiveness centered to the individual patients with whom decisions are to be made. Treatment decisions based on the evidence of the average patient are not optimized to reflect the unique clinical characteristics of an individual with JIA and their disease course, nor does it account for heterogeneous treatment effects. To guide treatment choices centered around each patient, we describe a novel concept of utilizing digital health technology to bring patient-centered information into shared decision-making discussions based on comparative effectiveness analysis of electronic health record or observational clinical registry data of patients with similar characteristics. The envisioned digital tool will organize and present data relevant to the individual patient and enable evidence-based individualized treatment decision making when used in a collaborative manner with the patient family and rheumatologist. Capabilities in digital health technology, data capturing, and analytical methodologies are ripe for this endeavor. This brings the concept of a learning health system directly to the point of care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Huang, Kouril, Chen, Daraiseh, Ferraro, Mannion, Brunner, Lovell and Morgan.)

Objectives: We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study., Methods: Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0., Results: Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48., Conclusions: In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48., Trial Registration Number: NCT01500551., Competing Interests: Competing interests: HIB has received research grants from Bristol Myers Squibb, Novartis and Pfizer; is an employee of Cincinnati Children’s Hospital Medical Center; has received consulting fees or other remuneration from AbbVie, AstraZeneca/MedImmune, Bayer, Biocon, Boehringer Ingelheim, Bristol Myers Squibb, Cerecor, Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Roche, R-Pharm and Sobi; and is a member of speaker bureaus for Novartis and Pfizer. JDA has received honorarium from Novartis. JFB has received research grants from AbbVie, Bristol Myers Squibb, Janssen, Pfizer and Roche. ALB is a member of speaker bureaus for AbbVie, Novartis and Roche. RC has received consulting fees or other remuneration from AbbVie, Bristol Myers Squibb, Eli Lilly, GSK, Novartis, Pfizer, Roche and Sanofi. GS has received consulting fees or other remuneration from Novartis and Sobi and research support from IpiNovyx. CN has received research grants from AbbVie, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GSK, Pfizer and UCB. MV-DM is an employee of Clínica de Investigacion en Reumatologia y Obesidad, SC. HP, CC, CWh, KeK and SL are employees and stockholders of Pfizer. AW was an employee and stockholder of Pfizer at the time of this analysis. AM has received consulting fees or other remuneration from Aurinia, Bristol Myers Squibb, Eli Lilly, EMD Serono, Janssen and Pfizer. DL’s institution, the Cincinnati Children’s Hospital Medical Center, has received research grants from Bristol Myers Squibb, Janssen, Novartis, Pfizer, Roche and UBC; and has received consulting fees or other remuneration from AstraZeneca, Boehringer Ingelheim, GSK, Roche, Novartis, Pfizer, Takeda and UBC. DL is also a data safety and monitoring board member or chairperson for the National Institutes of Health and the Canadian Arthritis Society. NR has received honoraria for consultancies or speaker bureaus from Ablynx, AstraZeneca/MedImmune, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, EMD Serono, F Hoffmann-La Roche, GS, Janssen, MSD, Novartis, Pfizer, R-Pharm, Sanofi, Servier, Sinergie and Sobi. The IRCCS Istituto Giannina Gaslini, where NR works as a full-time public employee, has received contributions from Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, GS, Janssen, Novartis, Pfizer and Sobi; this funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties. EA-A, GC, WDLP, LJ, ÖK, KaK, RR-C, JCRR, LW-W, JEW and CWo have declared no conflicts., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objectives: Childhood-onset systemic lupus erythematosus (cSLE), representing 15%-20% of individuals with SLE, has been difficult to study globally due to differences between registries. This initiative, supported by Childhood Arthritis Rheumatology Research Alliance (CARRA) and Paediatric Rheumatology European Society (PReS), aims to create Core and Expanded cSLE Datasets to standardise and enhance research worldwide., Methods: 21 international cSLE experts and 4 patients participated in a Delphi process (questionnaires, 2 topic-specific focus groups and 3 virtual consensus meetings) to create 2 standardised cSLE datasets. The Core cSLE Dataset was designed to include data essential to meaningful clinical research across many settings. The Expanded cSLE Dataset was designed for centres able to consistently collect data to address broader research questions. Final data items for the Core and Expanded datasets were determined by consensus defined as >80% agreement) using an adapted nominal group technique and voting., Results: The resulting Core cSLE Dataset contains 46 items, including demographics, clinical features, laboratory results, medications and significant adverse events. The Expanded cSLE Dataset adds 26 additional items and includes patient-reported outcomes. Consensus was also achieved regarding the frequency and time points for data collection: baseline, quarterly follow-up visits, annually and flare visits., Conclusion: Standardised Core and Expanded cSLE Datasets for registry-based international cSLE research were defined through the consensus of global experts and patient/caregiver representatives, endorsed by CARRA and PReS. These datasets incorporate disease-specific and patient-specific features, optimised for diverse settings to facilitate international collaborative research for children and adolescents with SLE worldwide., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objective: To validate the ankle-specific Pediatric Arthritis Ultrasound Scoring System (PAUSS-ankle) in children with juvenile idiopathic arthritis (JIA)., Methods: Patients with a diagnosis of JIA prospectively underwent a standard clinical assessment and musculoskeletal ultrasound (MSUS) of one or both ankles. B-mode and Power-Doppler mode MSUS images were acquired and scored according to the PAUSS-ankle protocol. A subset of patients received a contrast-enhanced MRI (ceMRI) of the affected ankle. ceMRI scoring for synovitis was performed according to the Rheumatoid Arthritis MRI System (RAMRIS). Test characteristics of the PAUSS-ankle scores were evaluated with ceMRI as reference. Associations between the findings on physical examination, PAUSS-ankle, and RAMRIS were investigated., Results: Thirty-two patients with JIA contributed 63 MSUS and 15 ceMRIs of the ankles. The PAUSS-ankle total B-mode score had a moderate correlation with physical examination findings (correlation (r)=0.43, p < 0.001). The PAUSS-ankle B-mode score ≥1 exhibited a sensitivity of 79 % and specificity of 100 %, demonstrating excellent diagnostic accuracy with an area under the curve (AUC)= 0.89 (confidence intervals, CI, 0.78-1.00) while clinical assessment had a sensitivity of 57 % and AUC= 0.71 (CI: 0.58-0.85). The PAUSS-ankle B-mode score had significant strong correlations (r = 0.68-0.90, p < 0.005) with the RAMRIS for the assessment of disease severity for each joint area and the ankle joint as a whole., Conclusion: Our findings demonstrate excellent diagnostic accuracy of the PAUSS-ankle in detecting the presence and severity of ankle synovitis when compared to ceMRI. The PAUSS-ankle holds significant promise as an accurate measurement that may complement current clinical standards., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare related to this publication. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This review will provide updates in the outcomes in the common rheumatologic diseases with kidney involvement. Covered are also advances in therapeutics for the use of pediatric rheumatologic diseases with kidney involvement, as well as the potential kidney complications from other rheumatologic diseases and their medications., Recent Findings: Two of the more common rheumatologic diseases with kidney involvement, lupus and vasculitis, continue to show inadequate response to initial therapy of renal disease and practice continues to be driven by results of adult studies., Summary: There is a continued need for pediatric specific studies in rheumatologic diseases with kidney involvement as outcomes continue to be inadequate. Despite recently approved treatments for adults with rheumatic diseases and kidney involvement, therapeutic options in pediatrics remain limited, contributing to the overall morbidity and mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to report the interim 5-year safety and effectiveness of abatacept in patients with JIA in the PRINTO/PRCSG registry., Methods: The Abatacept JIA Registry (NCT01357668) is an ongoing observational study of children with JIA receiving abatacept; enrolment started in January 2013. Clinical sites enrolled patients with JIA starting or currently receiving abatacept. Eligible patients were assessed for safety (primary end point) and effectiveness over 10 years. Effectiveness was measured by clinical 10-joint Juvenile Arthritis Disease Activity Score (cJADAS10) in patients with JIA over 5 years. As-observed analysis is presented according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines., Results: As of 31 March 2020, 587 patients were enrolled; 569 are included in this analysis (including 134 new users) with 1214.6 patient-years of safety data available. Over 5 years, the incidence rate (IR) per 100 patient-years of follow-up of serious adverse events was 5.52 (95% CI: 4.27, 7.01) and of events of special interest was 3.62 (95% CI: 2.63, 4.86), with 18 serious infections [IR 1.48 (95% CI: 0.88, 2.34)]. As early as month 3, 55.9% of patients achieved cJADAS10 low disease activity and inactive disease (20.3%, 72/354 and 35.6%, 126/354, respectively), sustained over 5 years. Disease activity measures improvement over 5 years across JIA categories., Conclusion: Abatacept was well tolerated in patients with JIA, with no new safety signals identified and with well-controlled disease activity, including some patients achieving inactive disease or remission., Trial Registration: Clinicaltrials.gov, NCT01357668., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA or sJIA)., Methods: Patients with pJIA or sJIA from two open-label, 52-week phase 1b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight-based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years, and safety for up to 5 years in the LTE., Results: Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 μg/ml; sJIA, ∼75 μg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection)., Conclusion: Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile., Clinical Trial Registration: clinicaltrials.gov, NCT02165345., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)