Individual outcomes after tailored versus generic self-management strategies for persistent fatigue in youth with a fatigue syndrome or rheumatic condition: A multiple single-case study.

OBJECTIVE: To examine individual outcomes after tailored lifestyle (PROfeel) or generic dietary advice as self-management intervention for persistent fatigue in adolescents and young adults with a chronic condition, to compare participants who did and did not benefit and to explore changes to factors in the biopsychosocial model of fatigue after PROfeel. METHOD: A multiple single-case AB-phase design was embedded in a randomized crossover trial (N = 45). Intensive longitudinal data (ILD) on outcomes 'fatigue severity', 'self-efficacy' and 'quality of life' (QoL) were collected through weekly smartphone measurement for 20 weeks. ILD on biopsychosocial factors were collected through experience sampling methodology for 28 days pre-post first intervention. Baseline characteristics were compared with t-tests and chi-square tests. Permutation distancing tests were used to assess change over time in all ILD. RESULTS: Regarding weekly measurements, nineteen participants (42.22%) showed small to large positive outcomes (drange = .05 to 2.59), mostly after PROfeel. Eleven participants (24.44%) showed small to moderate negative outcomes (drange = -.02 to -2.46), mostly after dietary advice. Fatigue severity improved most, followed by self-efficacy. Participants who benefitted showed higher QoL levels and lower fatigue and pain levels compared with others at baseline (all p < .02). When positive outcomes were observed after PROfeel, typically ≥1 biopsychosocial factor had been targeted successfully. CONCLUSION: Self-management advice has more potential when tailored to individual characteristics, including the biopsychosocial model of fatigue. PROfeel appears particularly useful as fatigue intervention for individuals with relatively less severe symptoms.

Humoral and cellular immunogenicity, effectiveness and safety of COVID-19 mRNA vaccination in patients with pediatric rheumatic diseases: A prospective cohort study.

OBJECTIVES: To evaluate immunogenicity, effectiveness and safety of COVID-19 vaccination in patients with pediatric autoimmune inflammatory rheumatic disease (pedAIIRD). METHODS: A prospective cohort study was performed at the pediatric rheumatology department of the Wilhelmina Children's Hospital in Utrecht, the Netherlands. Vaccination dates, COVID-19 cases and vaccine-related adverse events (AEs) were registered for all pedAIIRD patients during regular clinic visits from March 2021 - August 2022. SARS-CoV-2 IgG antibody levels and T-cell responses were measured from serum samples after vaccination, and clinical and drug therapy data were collected from electronic medical records. Rate of COVID-19 disease was compared between vaccinated and unvaccinated patients in a time-varying Cox regression analysis. RESULTS: A total of 157 patients were included in this study and 88 % had juvenile idiopathic arthritis (JIA). One hundred thirty-seven patients were fully vaccinated, of which 47 % used biological agents at the time of vaccination, and 20 patients were unvaccinated. Geometric mean concentrations (GMCs) of post-vaccine antibody levels against SARS-CoV-2 were above the threshold for positivity in patients who did and did not use biological agents at the time of vaccination, although biological users demonstrated significantly lower antibody levels (adjusted GMC ratio: 0.38, 95 % CI: 0.21 - 0.70). T-cell responses were adequate in all but two patients (9 %). The adjusted rate of reported COVID-19 was significantly lower for fully vaccinated patients compared to non-vaccinated patients (HR: 0.53, 95 % CI: 0.29 - 0.97). JIA disease activity scores were not significantly different after vaccination, and no serious AEs were reported. CONCLUSIONS: COVID-19 mRNA vaccines were immunogenic (both cellular and humoral), effective and safe in a large cohort of pedAIIRD patients despite their use of immunosuppressive medication.

Targeting persistent fatigue with tailored versus generic self-management strategies in adolescents and young adults with a fatigue syndrome or rheumatic condition: A randomized crossover trial.

OBJECTIVES: To evaluate the use of two self-management intervention strategies for persistent fatigue in adolescents and young adults with a fatigue syndrome or rheumatic condition. DESIGN: A randomized crossover trial administering tailored lifestyle advice and generic dietary advice, each 12 weeks, with a four-week washout period between. METHODS: Sixty participants (aged 12-29) were included. Tailoring was achieved through the PROfeel method. Dietary guidelines were conceptualized by the Netherlands Nutrition Centre. Questionnaires were used pre-post-interventions to measure primary outcome 'fatigue severity' (Checklist Individual Strength-8) and secondary outcomes 'self-efficacy' (Self-Efficacy Scale-28) and 'quality of life' (QoL) (Paediatric Quality of Life Inventory 4.0). Feasibility and adherence were self-rated on a scale of 1 to 10 (low to high). Linear mixed modelling was used to assess change over time, compare strategy effectiveness and study the impact of intervention order. RESULTS: Fatigue severity, self-efficacy and QoL regarding 'physical' and 'emotional' functioning improved significantly over time (all p < .015). The average improvement of the two QoL subscales was clinically relevant, as was the fatigue improvement in 20 out of 46 participants who completed the trial and 5 dropouts. The interventions were equally effective, and intervention order did not impact the improvement level (prange = .242-.984). The self-management strategies received similar feasibility (M = 6.45, SD = 1.91) and adherence (M = 7.67, SD = 1.67) ratings. CONCLUSIONS: As small to clinically relevant improvements were observed, self-management strategies might be particularly useful to bridge waiting time for guided treatments such as Cognitive Behavioural Therapy.

Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing tumour necrosis factor-alfa inhibitors in juvenile idiopathic arthritis.

OBJECTIVE: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNFi in JIA patients. METHODS: Retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were either immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalisation) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal). RESULTS: Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9,165/patient on active treatment (pre-withdrawal) and decreased significantly to €5,063/patient (-44.8%) and €6,569/patient (-28.3%) in the first and second year post-withdrawal, respectively (p< 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1,180/patient, and €1,320/patient, in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first, and second year post-withdrawal period, respectively. CONCLUSION: In the first two years after initiating withdrawal, the total annual costs are decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdraw decisions, future research should assess the full long-term societal cost impacts, and include all biologics.

The protective effect of COVID-19 vaccines on developing multisystem inflammatory syndrome in children (MIS-C): a systematic literature review and meta-analysis.

OBJECTIVE: To review whether the current COVID-19 vaccines can prevent the occurrence of multisystem inflammatory syndrome in children (MIS-C) and adolescents. METHODS: A systematic literature review and meta-analysis were performed. The data were abstracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Primary outcome was the efficacy of COVID-19 vaccination in preventing MIS-C development. The search was performed in PubMed and Embase. RESULTS: The review yielded 13 studies, which were included for critical appraisal and data extraction. The available studies showed a reduced incidence of MIS-C after mRNA COVID-19 vaccination in children aged 12-18 years. Four studies were eligible for meta-analysis and the pooled odds ratio for MIS-C in vaccinated children compared to unvaccinated children was 0.04 (95% confidence interval: 0.03-0.06). Additionally, the risk of MIS-C as an adverse effect of vaccination was much lower compared to the risk of MIS-C post-infection. CONCLUSIONS: Our systematic review highlights the current available evidence on the efficacy of COVID-19 vaccination in preventing MIS-C. The published studies so far - mainly conducted during the Delta wave - indicate that (original strain) COVID-19 mRNA vaccines in children are safe and associated with significantly less development of MIS-C. These findings further reinforce the recommendation for COVID-19 vaccination in children, which should be promoted and largely supported.

Clinically Established Temporomandibular Involvement in Adults With Juvenile Idiopathic Arthritis.

OBJECTIVE: To study clinical variables defining temporomandibular function in adults with juvenile idiopathic arthritis (JIA) and healthy controls. METHODS: In this cross-sectional study, the temporomandibular joint (TMJ) screening protocol, mandibular range of motion (MROM), and anterior maximum voluntary bite force (AMVBF) were compared between adults with JIA and healthy controls. Unadjusted and adjusted models with corrections for sex and disease duration were constructed for active maximum interincisal mouth opening (AMIO) and AMVBF. RESULTS: A total of 100 adults with JIA and 59 healthy adults were included in this study. In adults with JIA, 56% had clinically established TMJ involvement. AMIO was the MROM variable most reduced by TMJ involvement; AMIO was 8.8 mm (95% CI -11.40 to -6.12; P < 0.001) less in adults with JIA with TMJ involvement compared to JIA without TMJ involvement. No differences of AMIO were found between healthy adults and adults with JIA without TMJ involvement (-2.52, 95% CI -5.13 to 0.10; P = 0.06). Male sex was associated with a higher AMIO, and disease duration was associated with a decreased AMIO. Collinearity between the subtype prebiologic era and disease duration was found. AMVBF did not differ between adults with JIA and healthy adults. CONCLUSION: The high prevalence of clinically established TMJ involvement in adults with JIA indicates the need for awareness of TMJ problems in adults with JIA. TMJ involvement negatively influenced AMIO and should therefore be part of the TMJ screening in adults with JIA. AMVBF seems to have less utility for TMJ screening in adult populations.

Long-term immunoprotection after live attenuated measles-mumps-rubella booster vaccination in children with juvenile idiopathic arthritis.

INTRODUCTION: Vaccines, especially live attenuated vaccines, in children with JIA pose a great challenge due to both potential lower immunogenicity and safety as a result of immunosuppressive treatment. For many years, in the Netherlands, JIA patients receive a measles-mumps-rubella (MMR) booster vaccine at the age of nine years as part of the national immunization program. OBJECTIVES: To study long-term humoral immunoprotection in a large cohort of JIA patients who received the MMR booster vaccine while being treated with immunomodulatory therapies at the Wilhelmina Children's Hospital in Utrecht, the Netherlands. METHODS: MMR-specific IgG antibody concentrations in stored serum samples of vaccinated JIA patients were determined with chemiluminescent microparticle immunoassays (CMIA). Samples were analyzed five years after MMR booster vaccination and at last available follow-up visit using both crude and adjusted analyses. Additional clinical data were collected from electronic medical records. RESULTS: In total, 236 samples from 182 patients were analyzed, including 67 samples that were available five years post-vaccination, and an additional 169 samples available from last visits with a median duration after vaccination of 6.9 years (IQR: 2.8-8.8). Twenty-eight patients were using biologic disease-modifying antirheumatic drugs (bDMARDS) of whom 96% anti-TNF agents and 4% tocilizumab. Percentages of protective antibody levels against measles after five years were significantly lower for patients who used bDMARD therapy at vaccination compared to patients who did not: 60% versus 86% (P = 0.03). For mumps (80% versus 94%) and rubella (60% versus 83%) this difference did not reach statistical significance (P = 0.11 and P = 0.07, respectively). Antibody levels post-vaccination decreased over time, albeit not significantly different between bDMARD users and non-bDMARD users. CONCLUSION: The MMR booster vaccine demonstrated long-term immunogenicity in the majority of children with JIA from a large cohort, although lower percentages of protective measles antibody levels were observed in bDMARD users. Hence, it might be indicated to measure antibody levels at least five years after MMR booster vaccination in the latter group and advice an extra booster accordingly.

Meningococcal ACWY conjugate vaccine immunogenicity in adolescents with primary or secondary immune deficiencies, a prospective observational cohort study.

BACKGROUND: Immunization with meningococcal ACWY conjugate vaccine induces protective antibodies against invasive meningococcal disease (IMD) caused by serogroups A, C, W and Y. We studied MenACWY-TT vaccine immunogenicity in adolescents with a heterogenous group of primary and secondary immune deficiency including patients with systemic lupus erythematosus, mixed connective tissue disease, vasculitis, uveitis, 22Q11 syndrome, sickle cell disease, and patients who underwent stem cell transplantation for bone marrow failure. FINDINGS: We enrolled 69 individuals aged 14-18 years diagnosed with a primary or secondary immune deficiency in a prospective observational cohort study. All patients received a single dose of MenACWY-TT vaccine during the catch-up campaign 2018-19 because of the IMD-W outbreak in the Netherlands. Capsular polysaccharide-specific (PS) IgG concentrations against MenACWY were measured before and 3-6, 12, and 24 months after vaccination. Overall, geometric mean concentrations (GMCs) of MenACWY-PS-specific IgG were lower in patients compared to data from healthy, aged-matched controls (n = 75) reaching significance at 12 months postvaccination for serogroup A and W (adjusted GMC ratios 0.26 [95% CI: 0.15-0.47] and 0.22 [95% CI: 0.10-0.49], respectively). No serious adverse events were reported by study participants. CONCLUSIONS: The MenACWY conjugate vaccine was less immunogenic in adolescent patients with primary or secondary immunodeficiency compared to healthy controls, urging the need for further surveillance of these patients and supporting considerations for booster MenACWY conjugate vaccinations in these patient groups.

Meningococcal ACWY conjugate vaccine immunogenicity and safety in adolescents with juvenile idiopathic arthritis and inflammatory bowel disease: A prospective observational cohort study.

BACKGROUND: Immunogenicity to meningococcal serogroup ACWY (MenACWY) conjugate vaccine has not been studied in immunocompromised minors with juvenile idiopathic arthritis (JIA) or inflammatory bowel disease (IBD). We determined immunogenicity of a MenACWY-TT vaccine in JIA and IBD patients at adolescent age and compared results to data from aged-matched healthy controls (HCs). METHODS: We performed a prospective observational cohort study in JIA and IBD patients (14-18 years old), who received a MenACWY vaccination during a nationwide catch-up campaign (2018-2019) in the Netherlands. Primary aim was to compare MenACWY polysaccharide-specific serum IgG geometric mean concentrations (GMCs) in patients with HCs and secondary between patients with or without anti-TNF therapy. GMCs were determined before and 3-6, 12, and 24 months postvaccination and compared with data from HCs at baseline and 12 months postvaccination. Serum bactericidal antibody (SBA) titers were determined in a subset of patients at 12 months postvaccination. RESULTS: We included 226 JIA and IBD patients (66 % and 34 % respectively). GMCs were lower for MenA and MenW (GMC ratio 0·24 [0·17-0·34] and 0·16 [0·10-0·26] respectively, p < 0·01) in patients compared to HCs at 12 months postvaccination. Anti-TNF users had lower MenACWY GMCs postvaccination compared with those without anti-TNF (p < 0·01). The proportion protected (SBA ≥ 8) for MenW was reduced in anti-TNF users (76 % versus 92 % in non-anti-TNF and 100 % in HCs, p < 0.01). CONCLUSION: The MenACWY conjugate vaccine was immunogenic in the vast majority of JIA and IBD patients at adolescent age, but seroprotection was lower in patients using anti-TNF agents. Therefore, an extra booster MenACWY vaccination should be considered.

What matters most to pediatric rheumatologists in deciding whether to discontinue biologics in a child with juvenile idiopathic arthritis? A best-worst scaling survey.

OBJECTIVES: Care for JIA patients has been transformed in the biologics era; however, biologics carry important (although rare) risks and are costly. Flares after biological withdrawal are seen frequently, yet there is little clinical guidance to identify which patients in clinical remission can safely have their biologic discontinued (by stopping or tapering). We examined what characteristics of the child or their context are important to pediatric rheumatologists when making the decision to discuss withdrawal of biologics. METHODS: We conducted a survey including a best-worst scaling (BWS) exercise in pediatric rheumatologists who are part of the UCAN CAN-DU network to assess the relative importance of 14 previously identified characteristics. A balanced incomplete block design was used to generate choice tasks. Respondents evaluated 14 choice sets of 5 characteristics of a child with JIA and identified for each set which was the most and least important in the decision to offer withdrawal. Results were analyzed using conditional logit regression. RESULTS: Fifty-one (out of 79) pediatric rheumatologists participated (response rate 65%). The three most important characteristics were how challenging it was to achieve remission, history of established joint damage, and time spent in remission. The three least important characteristics were history of temporomandibular joint involvement, accessibility of biologics, and the patient's age. CONCLUSIONS: These findings give quantitative insight about factors important to pediatric rheumatologists' decision-making about biologic withdrawal. In addition to high quality clinical evidence, further research is needed to understand the perspective of patients and families to inform shared decision-making about biologic withdrawal for JIA patients with clinically inactive disease. Key Points ● What is already known on this topic-there is limited clinical guidance for pediatric rheumatologists in making decisions about biologic withdrawal for patients with juvenile idiopathic arthritis who are in clinical remission. ● What this study adds-this study quantitatively examined what characteristic of the child in clinical remission, or of their context, are most important to pediatric rheumatologists in deciding whether to offer withdrawal of biologics. ● How this study might affect research, practice or policy-understanding of these characteristics can provide useful information to other pediatric rheumatologists in making their decisions, and may guide areas to focus on for future research.

Methotrexate therapy associated with a reduced rate of new-onset uveitis in patients with biological-naïve juvenile idiopathic arthritis.

OBJECTIVE: To study the effect of methotrexate (MTX) therapy on new-onset uveitis in patients with biological-naïve juvenile idiopathic arthritis (JIA). METHODS: In this matched case-control study, we compared MTX exposure between cases with JIA-associated chronic uveitis (JIA-U) and patients with JIA and without JIA-U at the time of matching (controls). Data were collected from electronic health records of the University Medical Centre Utrecht, the Netherlands. Cases with JIA-U were matched 1:1 to JIA control patients based on JIA diagnosis date, age at JIA diagnosis, JIA subtype, antinuclear antibodies status and disease duration. The effect of MTX on JIA-U onset was analysed using a multivariable time-varying Cox regression analysis. RESULTS: Ninety-two patients with JIA were included and characteristics were similar between cases with JIA-U (n=46) and controls (n=46). Both ever-use of MTX and exposure years were lower in cases with JIA-U than in controls. Cases with JIA-U significantly more often discontinued MTX treatment (p=0.03) and out of those who did, 50% afterwards developed uveitis within 1 year. On adjusted analysis, MTX was associated with a significantly reduced new-onset uveitis rate (HR: 0.35; 95% CI: 0.17 to 0.75). No different effect was observed between a low (<10 mg/m2/week) and standard MTX dose (≥10 mg/m2/week). CONCLUSION: This study demonstrates an independent protective effect of MTX on new-onset uveitis in patients with biological-naïve JIA. Clinicians might consider early initiation of MTX in patients at high uveitis risk. We advocate more frequent ophthalmologic screening in the first 6-12 months after MTX discontinuation.

Safety of Measles-Mumps-Rubella booster vaccination in patients with juvenile idiopathic arthritis: A long-term follow-up study.

OBJECTIVES: To study short and long-term disease activity and vaccine-related adverse events in a cohort of JIA patients who received the live attenuated measles-mumps-rubella (MMR) booster vaccine while being treated with immunosuppressive and immunomodulatory therapies. METHODS: A retrospective study was performed in the UMC Utrecht, clinical and therapeutic data were collected from electronic medical records for two visits before and two visits after the MMR booster vaccine of JIA patients. Drug therapy was collected and adverse events related to the vaccine were requested from the patients during clinical visits or by short phone interviews. Associations between MMR booster vaccination and the active joint count, physician global assessment of disease activity, patient-reported visual analogue scale (VAS) for well-being and clinical Juvenile Arthritis Disease Activity Score (cJADAS) were analyzed using multivariable linear mixed effects analyses. RESULTS: A total of 186 JIA patients were included in the study. At the time of vaccination, 51% of the patients used csDMARD and 28% used bDMARD therapy. Overall, adjusted disease activity scores after MMR booster vaccination were not significantly different compared to pre-vaccination. Mild adverse events related to the MMR booster were reported for 7% of the patients. No serious adverse events were reported. CONCLUSION: MMR booster vaccination was safe and did not worsen disease activity during long-term follow-up in a large cohort of JIA patients being treated with both csDMARDs and biological DMARDs.

Cross-Cultural Adaptation and Validation of the Methotrexate Intolerance Severity Score Questionnaire in Portuguese (Brazil) for Children and Adolescents with Juvenile Idiopathic Arthritis.

The Methotrexate (MTX) Intolerance Severity Score (MISS) questionnaire has been developed to identify MTX adverse events in juvenile idiopathic arthritis (JIA). The objective of this study was to translate and validate MISS into Brazilian Portuguese for children and adolescents. The MISS was translated into Portuguese following the standardized guidelines. We analyzed the following psychometric properties: acceptability, internal consistency, test-retest reproducibility, relative-child reliability, and external criterion and discriminant validity. We included 138 JIA patients (age: 8-18 years) and 108 relatives who took less than 5 min to answer MISS. Reproducibility tested after 15 days was good, with a kappa > 0.76. We observed good internal consistency (Cronbach's coefficient 0.75-0.87 (patients) and 0.75-0.79 (relatives)). Reliability between patients and relatives was good except for stomachache and restlessness. Cut-off points of 5 and 6 had good sensitivity (84 and 71, respectively) and specificity (80 and 87, respectively). Using a cut-off value of 6, we observed 86 (62.3%) MTX-intolerant patients. In conclusion, MISS is a viable and practical tool for routine clinical care to identify MTX intolerance in JIA. Parents do not easily identify stomachache and restlessness as adverse MTX events.

Dynamic modeling of experience sampling methodology data reveals large heterogeneity in biopsychosocial factors associated with persistent fatigue in young people living with a chronic condition.

OBJECTIVE: To evaluate associations between self-reported biopsychosocial factors and persistent fatigue with dynamic single-case networks. METHODS: 31 persistently fatigued adolescents and young adults with various chronic conditions (aged 12 to 29 years) completed 28 days of Experience Sampling Methodology (ESM) with five prompts per day. ESM surveys consisted of eight generic and up to seven personalized biopsychosocial factors. Residual Dynamic Structural Equation Modeling (RDSEM) was used to analyze the data and derive dynamic single-case networks, controlling for circadian cycle effects, weekend effects, and low-frequency trends. Networks included contemporaneous and cross-lagged associations between biopsychosocial factors and fatigue. Network associations were selected for evaluation if both significant (α < 0.025) and relevant (ß ≥ 0.20). RESULTS: Participants chose 42 different biopsychosocial factors as personalized ESM items. In total, 154 fatigue associations with biopsychosocial factors were found. Most associations were contemporaneous (67.5%). Between chronic condition groups, no significant differences were observed in the associations. There were large inter-individual differences in which biopsychosocial factors were associated with fatigue. Contemporaneous and cross-lagged associations with fatigue varied widely in direction and strength. CONCLUSIONS: The heterogeneity found in biopsychosocial factors associated with fatigue underlines that persistent fatigue stems from a complex interplay between biopsychosocial factors. The present findings support the need for personalized treatment of persistent fatigue. Discussing the dynamic networks with the participant can be a promising step towards tailored treatment. TRIAL REGISTRATION: No. NL8789 (http://www.trialregister.nl).

Juvenile idiopathic arthritis patients with positive family history of autoimmune thyroid disease might benefit from serological screening: analysis of the international Pharmachild registry.

BACKGROUND: Little is known about the association between juvenile idiopathic arthritis (JIA) and autoimmune thyroid disease (AITD) and therefore there are no indications for AITD screening in this population, which is possible using standard blood tests. The objective of this study is to determine the prevalence and predictors of symptomatic AITD in JIA patients from the international Pharmachild registry. METHODS: Occurrence of AITD was determined from adverse event forms and comorbidity reports. Associated factors and independent predictors for AITD were determined using univariable and multivariable logistic regression analyses. RESULTS: The prevalence of AITD after a median observation period of 5.5 years was 1.1% (96/8965 patients). Patients who developed AITD were more often female (83.3% vs. 68.0%), RF positive (10.0% vs. 4.3%) and ANA positive (55.7% vs. 41.5%) than patients who did not. AITD patients were furthermore older at JIA onset (median 7.8 years vs. 5.3 years) and had more often polyarthritis (40.6% vs. 30.4%) and a family history of AITD (27.5% vs. 4.8%) compared to non-AITD patients. A family history of AITD (OR = 6.8, 95% CI: 4.1 - 11.1), female sex (OR = 2.2, 95% CI: 1.3 - 4.3), ANA positivity (OR = 2.0, 95% CI: 1.3 - 3.2) and older age at JIA onset (OR = 1.1, 95% CI: 1.1 - 1.2) were independent predictors of AITD on multivariable analysis. Based on our data, 16 female ANA positive JIA patients with a family history of AITD would have to be screened during ±5.5 years using standard blood tests to detect one case of AITD. CONCLUSIONS: This is the first study to report independent predictor variables for symptomatic AITD in JIA. Female ANA positive JIA patients with positive family history are at increased risk of developing AITD and thus might benefit from yearly serological screening.

Reliability and measurement error of anterior maximum voluntary bite force in children with juvenile idiopathic arthritis and healthy children.

In children with juvenile idiopathic arthritis (JIA) the temporomandibular joint (TMJ) can be involved. As a consequence, the oral function can be impaired due to joint and/or muscle involvement of the masticatory system with a negative influence on the maximum bite force. The aim of this cross-sectional study was to establish the reliability of AMVBF in children with JIA and healthy children. Children with JIA and healthy children conducted three attempts of AMVBF. The reliability of AMVBF measurement was determined by the intra-class correlation coefficient (ICC) by age, standard error of measurement (SEM), smallest detectable change (SDC), and limits of agreement (LoA). A total of 298 children with JIA and 168 healthy children were examined. The AMVBF measurements showed an good to excellent reliability in children with JIA based on the ICCs corrected for age (0.782-0.979). In healthy children, the reliability was moderate to excellent (0.546-0.999). The SDC in our study indicated that values above 11.4N might be a clinical relevant change over time in children with JIA. The LoA showed a wide spread of variability in both children with JIA (-72.6-44.4N) and healthy children (-79.9-72.8N). The Bland-Altman plots indicated that the differences between the test and retest increased in value proportionally to the biteforce value.

Patients' and parents' satisfaction to improve patient care in JIA: factors determining acceptable symptom state measured with JAMAR.

OBJECTIVES: The aim of this study was to identify factors associated with patients' and parents' reported satisfaction with JIA care, measured with the juvenile arthritis child and parent acceptable symptom state (JA-CASS and JA-PASS, respectively). METHODS: A prospective cohort of 239 JIA patients and 238 parents in a tertiary centre who completed the juvenile arthritis multidimensional assessment report (JAMAR) was analysed cross-sectionally. The primary outcomes were positive JA-CASS and JA-PASS, respectively. Items in the JAMAR, as well as JIA subtype, demographics, and disease activity parameters, were analysed in univariate analysis. A multivariable logistic regression analysis was used to build models explaining the variance of the primary outcome as a dependent variable. RESULTS: According to the JAMAR, 141 (59.0%) of 239 patients and 149 (62.6%) of 238 parents were satisfied with their or their child's current condition. For patients, the determinants in the final model were a shorter duration of morning stiffness (P = 0.001), a lower age at disease onset (P = 0.044), a longer disease duration (P = 0.009) and a higher rating of the patient's well-being measured on a visual analogue scale (VAS) (P = 0.004). For parents, the determinants were the current state of disease activity (current state of persistent activity P = 0.002, relapse P < 0.005), problems at school (P = 0.002) and the items regarding quality of life (QoL) (P = 0.005). CONCLUSION: Our data highlight the importance of patients' and parents' opinions in the evaluation of disease activity, and support their integration into the shared decision-making in daily clinical practice to improve the quality of medical care.

Development and External Validation of a Model Predicting New-Onset Chronic Uveitis at Different Disease Durations in Juvenile Idiopathic Arthritis.

OBJECTIVE: To develop and externally validate a prediction model for new-onset chronic uveitis in children with juvenile idiopathic arthritis (JIA) for clinical application. METHODS: Data from the international Pharmachild registry were used to develop a multivariable Cox proportional hazards model. Predictors were selected by backward selection, and missing values were handled by multiple imputation. The model was subsequently validated and recalibrated in 2 inception cohorts: the UK Childhood Arthritis Prospective Study (CAPS) study and the German Inception Cohort of Newly diagnosed patients with juvenile idiopathic arthritis (ICON) study. Model performance was evaluated by calibration plots and C statistics for the 2-, 4-, and 7-year risk of uveitis. A diagram and digital risk calculator were created for use in clinical practice. RESULTS: A total of 5,393 patients were included for model development, and predictor variables were age at JIA onset (hazard ratio [HR] 0.83 [95% confidence interval (95% CI) 0.77-0.89]), ANA positivity (HR 1.59 [95% CI 1.06-2.38]), and International League of Associations for Rheumatology category of JIA (HR for oligoarthritis, psoriatic arthritis, and undifferentiated arthritis versus rheumatoid factor-negative polyarthritis 1.40 [95% CI 0.91-2.16]). Performance of the recalibrated prediction model in the validation cohorts was acceptable; calibration plots indicated good calibration and C statistics for the 7-year risk of uveitis (0.75 [95% CI 0.72-0.79] for the ICON cohort and 0.70 [95% CI 0.64-0.76] for the CAPS cohort). CONCLUSION: We present for the first time a validated prognostic tool for easily predicting chronic uveitis risk for individual JIA patients using common clinical parameters. This model could be used by clinicians to inform patients/parents and provide guidance in choice of uveitis screening frequency and arthritis drug therapy.

Prevalence of familial autoimmune diseases in juvenile idiopathic arthritis: results from the international Pharmachild registry.

BACKGROUND: Little is known about the disposition to autoimmune diseases (ADs) among children diagnosed with JIA. In this study, we provide a comprehensive overview of the prevalence of and factors associated with ADs in parents of children with juvenile idiopathic arthritis (JIA). METHODS: Prevalence rates of ADs and 95% Poisson confidence intervals were calculated for parents of JIA patients from the international Pharmachild registry and compared with general population prevalence rates as reported in the literature. Demographic, clinical and laboratory features were compared between JIA patients with and without a family history of AD using χ2 and Mann-Whitney U tests. RESULTS: Eight thousand six hundred seventy three patients were included and the most common familial ADs were psoriasis, autoimmune thyroid disease, rheumatoid arthritis and ankylosing spondylitis. The prevalence of several ADs was higher in parents of the included JIA patients than in the general population. Clinical Juvenile Arthritis Disease Activity Scores at study entry and last follow-up were not significantly different between patients with (n = 1231) and without a family history of AD (n = 7442). Factors associated with familial AD were older age at JIA onset (P < 0.01), Scandinavian residence (P < 0.01), enthesitis-related arthritis, psoriatic arthritis and undifferentiated arthritis (P < 0.01), ANA positivity (P = 0.03) and HLA-B27 positivity (P < 0.01). CONCLUSIONS: Familial AD proves to be a risk factor for JIA development and certain diseases should therefore not be overlooked during family health history at the diagnosis stage. A family history of AD is associated with the JIA category but does not influence the severity or disease course.

Real-world comparison of the effects of etanercept and adalimumab on well-being in non-systemic juvenile idiopathic arthritis: a propensity score matched cohort study.

BACKGROUND: Etanercept (ETN) and adalimumab (ADA) are considered equally effective biologicals in the treatment of arthritis in juvenile idiopathic arthritis (JIA) but no studies have compared their impact on patient-reported well-being. The objective of this study was to determine whether ETN and ADA have a differential effect on patient-reported well-being in non-systemic JIA using real-world data. METHODS: Biological-naive patients without a history of uveitis were selected from the international Pharmachild registry. Patients starting ETN were matched to patients starting ADA based on propensity score and outcomes were collected at time of therapy initiation and 3-12 months afterwards. Primary outcome at follow-up was the improvement in Juvenile Arthritis Multidimensional Assessment Report (JAMAR) visual analogue scale (VAS) well-being score from baseline. Secondary outcomes at follow-up were decrease in active joint count, adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed effects models. RESULTS: Out of 158 eligible patients, 45 ETN starters and 45 ADA starters could be propensity score matched resulting in similar VAS well-being scores at baseline. At follow-up, the median improvement in VAS well-being was 2 (interquartile range (IQR): 0.0 - 4.0) and scores were significantly better (P = 0.01) for ETN starters (median 0.0, IQR: 0.0 - 1.0) compared to ADA starters (median 1.0, IQR: 0.0 - 3.5). The estimated mean difference in VAS well-being improvement from baseline for ETN versus ADA was 0.89 (95% CI: -0.01 - 1.78; P = 0.06). The estimated mean difference in active joint count decrease was -0.36 (95% CI: -1.02 - 0.30; P = 0.28) and odds ratio for adverse events was 0.48 (95% CI: 0.16 -1.44; P = 0.19). One uveitis event was observed in the ETN group. CONCLUSIONS: Both ETN and ADA improve well-being in non-systemic JIA. Our data might indicate a trend towards a slightly stronger effect for ETN, but larger studies are needed to confirm this given the lack of statistical significance.