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Pediatric Rheumatology Online Journal Oct 2021Juvenile Idiopathic Arthritis (JIA) requires complex care that generate elevated costs, which results in a high economic impact for the family. The aim of this...
BACKGROUND
Juvenile Idiopathic Arthritis (JIA) requires complex care that generate elevated costs, which results in a high economic impact for the family. The aim of this systematic review was to collect and cluster the information currently available on healthcare costs associated with JIA after the introduction of biological therapies.
METHODS
We comprehensively searched in MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Databases for studies from January 2000 to March 2021. Reviewers working independently and in duplicate appraised the quality and included primary studies that report total, direct and/or indirect costs related to JIA for at least one year. The costs were converted to United States dollars and an inflationary adjustment was made.
RESULTS
We found 18 eligible studies including data from 6,540 patients. Total costs were reported in 10 articles, ranging from $310 USD to $44,832 USD annually. Direct costs were reported in 16 articles ($193 USD to $32,446 USD), showing a proportion of 55 to 98 % of total costs. Those costs were mostly related to medications and medical appointments. Six studies reported indirect costs ($117 USD to $12,385 USD). Four studies reported costs according to JIA category observing the highest in polyarticular JIA. Total and direct costs increased up to three times after biological therapy initiation. A high risk of reporting bias and inconsistency of the methodology used were found.
CONCLUSION
The costs of JIA are substantial, and the highest are derived from medication and medical appointments. Indirect costs of JIA are underrepresented in costs analysis.
Topics: Arthritis, Juvenile; Cost of Illness; Cost-Benefit Analysis; Health Care Costs; Humans
PubMed: 34627296
DOI: 10.1186/s12969-021-00641-y -
Pediatric Rheumatology Online Journal Apr 2023To develop and evaluate German versions of the Parent Adherence Report Questionnaire (PARQ) and Child Adherence Report Questionnaire (CARQ) and to evaluate adherence in...
OBJECTIVES
To develop and evaluate German versions of the Parent Adherence Report Questionnaire (PARQ) and Child Adherence Report Questionnaire (CARQ) and to evaluate adherence in patients with juvenile idiopathic arthritis (JIA).
METHODS
The PARQ and CARQ were translated into German, cross-culturally adapted and administered to patients (age ≥ 8 years) and their parents enrolled in the Inception Cohort Study of newly diagnosed JIA patients (ICON). The psychometric issues were explored by analyzing their test-retest reliability and construct validity.
RESULTS
Four hundred eighty-one parents and their children with JIA (n = 465) completed the PARQ and CARQ at the 4-year follow-up. Mean age and disease duration of patients were 10.1 ± 3.7 and 4.7 ± 0.8 years, respectively. The rate of missing values for PARQ/CARQ was generally satisfactory, test-retesting showed sufficient reliability. PARQ/CARQ mean child ability total scores (0-100, 100 = best) for medication were 73.1 ± 23.3/76.5 ± 24.2, for exercise: 85.6 ± 16.5/90.3 ± 15.0, for splints: 72.9 ± 24.2/82.9 ± 16.5. Construct validity was supported by PARQ and CARQ scores for medications, exercise and splints showing a fair to good correlation with the Global Adherence Assessment (GAA) and selected PedsQL scales. Adolescents showed poorer adherence than children. About one third of the parents and children reported medication errors. Perceived helpfulness was highest for medication, and adverse effects were reported the greatest barrier to treatment adherence.
CONCLUSIONS
The German versions of the PARQ and CARQ appear to have a good reliability and sufficient construct validity. These questionnaires are valuable tools for measuring treatment adherence, identifying potential barriers and evaluating helpfulness of treatments in patients with JIA.
Topics: Child; Adolescent; Humans; Arthritis, Juvenile; Quality of Life; Cohort Studies; Reproducibility of Results; Exercise; Parents; Psychometrics; Translating; Disability Evaluation; Health Status; Case-Control Studies
PubMed: 37046303
DOI: 10.1186/s12969-023-00811-0 -
BMC Pediatrics Mar 2021Phenylketonuria (PKU) is a genetic metabolic disorder in which patients have no ability to convert phenylalanine to tyrosine. Several autoimmune diseases have been...
BACKGROUND
Phenylketonuria (PKU) is a genetic metabolic disorder in which patients have no ability to convert phenylalanine to tyrosine. Several autoimmune diseases have been reported to combine with PKU, co-existent of PKU and Juvenile Idiopathic Arthritis (JIA) has not been presented.
CASE PRESENTATION
The girl was diagnosed with PKU at the age of 1 month confirmed by molecular data. At the age of 3.5 years, she presented with pain and swelling of her right ankle, right knee, and right hip joint. After a serial of examinations, she was diagnosed with JIA and treated with a nonsteroidal anti-inflammatory drug.
CONCLUSIONS
We report a rare case of a 4-year-old girl with PKU and JIA, which supports a possible interaction between PKU and JIA. Long-term metabolic disturbance may increase the susceptibility to JIA. Further chronic inflammation could alter the metabolism of tryptophan and tyrosine to increase blood Phe concentration. In addition, corticosteroid and methotrexate therapy for JIA may increase blood Phe concentration.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Child, Preschool; Female; Humans; Phenylalanine; Phenylketonurias
PubMed: 33722205
DOI: 10.1186/s12887-021-02602-6 -
Pediatric Rheumatology Online Journal Sep 2022Kinesiophobia may hinder physical performance measures and functional quality of life in children with juvenile idiopathic arthritis (JIA). This study aims to quantify...
BACKGROUND
Kinesiophobia may hinder physical performance measures and functional quality of life in children with juvenile idiopathic arthritis (JIA). This study aims to quantify differences in physical function in patients with JIA compared to healthy controls, and determine the effects of kinesiophobia on physical function and physical activity.
METHODS
This was a comparative study of participants with JIA and healthy controls (JIA n = 26, control n = 17). All children with JIA had lower extremity joint involvement. Performance-based measures included gait speed, chair and stair navigation performance. Self-reported measures included Patient Reported Outcome Measurement Information System (PROMIS®) Physical Function Mobility, and Pain Interference and the Pediatric Functional Activity Brief Scale (Pedi-FABS). The Tampa Scale of Kinesiophobia (TSK-11) assessed patient fear of movement due to pain. Linear regression models were used to determine the contribution of TSK-11 scores on performance test and Pedi-FABS scores.
RESULTS
Gait speeds were 11-15% slower, chair rise repetitions were 28% fewer, and stair ascent and descent times were 26-31% slower in JIA than controls (p < .05). PROMIS® Physical Function Mobility scores were 10% lower and Pain Interference scores were 2.6 times higher in JIA than healthy controls (p = .003). TSK-11 scores were higher in JIA than controls (p < .0001). After controlling for covariates, TSK-11 scores explained 11.7-26.5% of the variance of regression models for stair climb time, chair rise performance and Pedi-FABS scores (p < .05).
CONCLUSIONS
Children with JIA experience difficulty with tasks related to body transfers. Kinesiophobia is a significant contributor to the functional task performance and may impact clinical outcomes.
Topics: Arthritis, Juvenile; Child; Exercise; Humans; Pain; Patient Reported Outcome Measures; Quality of Life
PubMed: 36050703
DOI: 10.1186/s12969-022-00734-2 -
Seminars in Arthritis and Rheumatism Aug 2021Pain is prevalent in juvenile idiopathic arthritis (JIA). Unknowns regarding the biological drivers of pain complicate therapeutic targeting. We employed neuroimaging...
INTRODUCTION
Pain is prevalent in juvenile idiopathic arthritis (JIA). Unknowns regarding the biological drivers of pain complicate therapeutic targeting. We employed neuroimaging to define pain-related neurobiological features altered in JIA.
METHODS
16 male and female JIA patients (12.7 ± 2.8 years of age) on active treatment were enrolled, together with age- and sex-matched controls. Patients were assessed using physical examination, clinical questionnaires, musculoskeletal MRI, and structural neuroimaging. In addition, functional magnetic resonance imaging (fMRI) data were collected during the resting-state, hand-motor task performance, and cold stimulation of the hand and knee.
RESULTS
Patients with and without pain and with and without inflammation (joint and systemic) were evaluated. Pain severity was associated with more physical stress and poorer cognitive function. Corrected for multiple comparisons, morphological analysis revealed decreased cortical thickness within the insula cortex and a negative correlation between caudate nucleus volume and pain severity. Functional neuroimaging findings suggested alteration within neurocircuitry structures regulating emotional pain processing (anterior insula) in addition to the default-mode and sensorimotor networks.
CONCLUSIONS
Patients with JIA may exhibit changes in neurobiological circuits related to pain. These preliminary findings suggest mechanisms by which pain could potentially become dissociated from detectable joint pathology and persist independently of inflammation or treatment status.
Topics: Arthritis, Juvenile; Female; Humans; Knee Joint; Magnetic Resonance Imaging; Male; Pain; Pain Measurement
PubMed: 34139523
DOI: 10.1016/j.semarthrit.2021.05.011 -
The Cochrane Database of Systematic... Oct 2022Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and a potentially sight-threatening condition characterized by... (Review)
Review
BACKGROUND
Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis (JIA) and a potentially sight-threatening condition characterized by intraocular inflammation. Current treatment for JIA-associated uveitis (JIA-U) is largely based on physician experience, observational evidence and consensus guidelines, resulting in considerable variations in practice. OBJECTIVES: To evaluate the effectiveness and safety of tumor necrosis factor (TNF) inhibitors used for treatment of JIA-U.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We last searched the electronic databases on 3 February 2022.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) comparing TNF inhibitors with placebo in participants with a diagnosis of JIA and uveitis who were aged 2 to 18 years old.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology and graded the certainty of the body of evidence for seven outcomes using the GRADE classification.
MAIN RESULTS
We included three RCTs with 134 participants. One study conducted in the USA randomized participants to etanercept or placebo (N = 12). Two studies, one conducted in the UK (N = 90) and one in France (N = 32), randomized participants to adalimumab or placebo. All studies were at low risk of bias. Initial pooled estimates suggested that TNF-inhibitors may result in little to no difference on treatment success defined as 0 to trace cells on Standardization of Uveitis Nomenclature (SUN)-grading; or two-step decrease in activity based on SUN grading (estimated risk ratio (RR) 0.66; 95% confidence interval (CI) 0.21 to 2.10; 2 studies; 43 participants; low-certainty evidence) or treatment failure defined as a two-step increase in activity based on SUN grading (RR 0.31; 95% CI 0.01 to 7.15; 1 study; 31 participants; low-certainty evidence). Further analysis using the individual trial definitions of treatment response and failure suggested a positive treatment effect of TNF inhibitors; a RR of treatment success of 2.60 (95% CI 1.30 to 5.20; 3 studies; 124 participants; low-certainty evidence), and RR of treatment failure of 0.23 (95% CI 0.11 to 0.50; 3 studies; 133 participants). Almost all the evidence was on adalimumab and the evidence on etanercept was very limited. For secondary outcomes, one study suggests that adalimumab may have little to no effect on risk of recurrence after induction of remission at three months (RR 2.50, 95% CI 0.31 to 20.45; 90 participants; very low-certainty evidence) and visual acuity, but the evidence is very uncertain; mean difference in longitudinal logMAR score change over six months was -0.01 (95% CI -0.06 to 0.03) and -0.02 (95% CI -0.07 to 0.03) using the best and worst logMAR measurement, respectively (low-certainty evidence). Low-certainty evidence from one study suggested that adalimumab treatment results in reduction of topical steroid doses at six months (hazard ratio 3.58; 95% CI 1.24 to 10.32; 74 participants who took one or more topical steroid per day at baseline). Adverse events, including injection site reactions and infections, were more common in the TNF inhibitor group. Serious adverse events were uncommon.
AUTHORS' CONCLUSIONS
Adalimumab appears to increase the likelihood of treatment success and decrease the likelihood of treatment failure when compared with placebo. The evidence was less conclusive about a positive treatment effect with etanercept. Adverse events from JIA-U trials are in keeping with the known side effect profile of TNF inhibitors. Standard validated JIA-U outcome measures are required to homogenize assessment and to allow for comparison and analysis of multiple datasets.
Topics: Adalimumab; Adolescent; Arthritis, Juvenile; Child; Child, Preschool; Etanercept; Humans; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Uveitis
PubMed: 36239193
DOI: 10.1002/14651858.CD013818.pub2 -
Journal of Clinical Immunology Jan 2023Systemic juvenile idiopathic arthritis associated with interstitial lung disease (SJIA-LD) represents a highly morbid subset of SJIA for which effective therapies are...
Systemic juvenile idiopathic arthritis associated with interstitial lung disease (SJIA-LD) represents a highly morbid subset of SJIA for which effective therapies are lacking. We report the case of a patient with refractory SJIA-LD who underwent treatment with MAS-825, an investigational bispecific monoclonal antibody targeting IL-1β and IL-18. MAS-825 treatment was associated with a marked reduction in total IL-18 and free IL-18 in both serum and bronchoalveolar lavage fluid (BAL). Baseline oxygen saturation, exercise tolerance, and quality of life metrics improved after treatment with MAS-825, while pulmonary function testing remained stable. Following treatment, the BAL showed no evidence of pulmonary alveolar proteinosis and inflammatory infiltrates were markedly reduced, reflected by decreased numbers of CD4 T-cells, CD8 T-cells, and macrophages. The patient was able to wean entirely off systemic corticosteroids and other biologics after 10 months of treatment with MAS-825 and experienced no side effects of the drug. This case demonstrates improvement in pulmonary symptoms, lung inflammation, and burden of immunomodulatory therapy after treatment with MAS-825 and suggests that simultaneous targeting of both IL-1β and IL-18 may be a safe and effective treatment strategy in SJIA-LD.
Topics: Humans; Interleukin-18; Arthritis, Juvenile; Quality of Life; Macrophage Activation Syndrome; Lung Diseases, Interstitial
PubMed: 36006569
DOI: 10.1007/s10875-022-01353-y -
Pediatric Rheumatology Online Journal Nov 2023Juvenile Idiopathic Arthritis (JIA) is the most common form of childhood inflammatory arthritis. The disease burden of JIA is substantial as patients require specialized... (Review)
Review
Reporting of determinants of health inequities and participant characteristics in randomized controlled trials of juvenile idiopathic arthritis in Canada: a scoping review.
BACKGROUND
Juvenile Idiopathic Arthritis (JIA) is the most common form of childhood inflammatory arthritis. The disease burden of JIA is substantial as patients require specialized medical practitioners for diagnosis and chronic treatments that are both costly and time intensive. Discrepancies in access to care due to health inequities such as socioeconomic status or geographic location may lead to vastly different health outcomes. As research informs advances in care, is important to consider inclusion and diversity in JIA research.
METHODS
We reviewed and synthesized randomized controlled trials for juvenile idiopathic arthritis, the most common type of arthritis among children and adolescents, in Canada with the aim of characterizing participants and identifying how determinants of health inequities are reported. To do so, we searched Medline (1990 to July 2022), Embase (1990 to July 2022), and CENTRAL (inception to July 2022) for articles meeting all of the following criteria: Canadian randomized controlled trials evaluating pharmacological or non-pharmacological interventions on juvenile idiopathic arthritis populations. Data extraction was guided by the Campbell and Cochrane Equity Methods Group's PROGRESS-Plus framework on determinants that lead to health inequities (e.g., Place of residence; Race; Occupation; Gender/Sex; Religion; Education; Socioeconomic status; and Social capital).
RESULTS
Of 4,074 unique records, 5 were deemed eligible for inclusion. From these determinants of health inequities, Gender/Sex and Age were the only that were reported in all studies with most participants being female and 12.6 years old on average. In addition, Race, Socioeconomic status, Education and Features of relationships were each reported once in three different studies. Lastly, Place of residence, Occupation, Religion, Social Capital and Time-dependent relationships were not reported at all.
CONCLUSIONS
This scoping review suggests limited reporting on determinants of health inequities in randomized controlled trials for JIA in Canada and a need for a reporting framework that reflects typical characteristics of juvenile patient populations.
Topics: Child; Adolescent; Humans; Female; Male; Arthritis, Juvenile; Canada; Randomized Controlled Trials as Topic; Health Inequities
PubMed: 37932754
DOI: 10.1186/s12969-023-00917-5 -
Clinical Rheumatology Oct 2021Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility...
BACKGROUND
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition of childhood. Genetic association studies have revealed several JIA susceptibility loci with the strongest effect size observed in the human leukocyte antigen (HLA) region. Genome-wide association studies have augmented the number of JIA-associated loci, particularly for non-HLA genes. The aim of this study was to identify new associations at non-HLA loci predisposing to the risk of JIA development in Estonian patients.
METHODS
We performed genome-wide association analyses in an entire JIA case-control sample (All-JIA) and in a case-control sample for oligoarticular JIA, the most prevalent JIA subtype. The entire cohort was genotyped using the Illumina HumanOmniExpress BeadChip arrays. After imputation, 16,583,468 variants were analyzed in 263 cases and 6956 controls.
RESULTS
We demonstrated nominal evidence of association for 12 novel non-HLA loci not previously implicated in JIA predisposition. We replicated known JIA associations in CLEC16A and VCTN1 regions in the oligoarticular JIA sample. The strongest associations in the All-JIA analysis were identified at PRKG1 (P = 2,54 × 10), LTBP1 (P = 9,45 × 10), and ELMO1 (P = 1,05 × 10). In the oligoarticular JIA analysis, the strongest associations were identified at NFIA (P = 5,05 × 10), LTBP1 (P = 9,95 × 10), MX1 (P = 1,65 × 10), and CD200R1 (P = 2,59 × 10).
CONCLUSION
This study increases the number of known JIA risk loci and provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis. The reported loci are involved in molecular pathways of immunological relevance and likely represent genomic regions that confer susceptibility to JIA in Estonian patients. Key Points • Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease with heterogeneous presentation and genetic predisposition. • Present genome-wide association study for Estonian JIA patients is first of its kind in Northern and Northeastern Europe. • The results of the present study increase the knowledge about JIA risk loci replicating some previously described associations, so adding weight to their relevance and describing novel loci. • The study provides additional evidence for the existence of overlapping genetic risk loci between JIA and other autoimmune diseases, particularly rheumatoid arthritis.
Topics: Arthritis, Juvenile; Case-Control Studies; Estonia; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide
PubMed: 34101054
DOI: 10.1007/s10067-021-05756-x -
Bosnian Journal of Basic Medical... Apr 2022Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and...
Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood-onset inflammatory disease characterized by arthritis accompanied by systemic auto-inflammation and extra-articular symptoms. While recent advances have unraveled a range of risk factors, the pathomechanisms involved in SJIA and potential prognostic markers for treatment success remain partly unknown. In this study, we included 70 active SJIA and 55 healthy control patients from the National Center for Biotechnology Information to analyze for differentially expressed genes (DEGs) using R. Functional enrichment analysis, protein-protein interaction (PPI), and gene module construction were performed for DEGs and hub gene set. We additionally examined immune system cell composition with CIBERSORT and predicted prognostic markers and potential treatment drugs for SJIA. In total, 94 upregulated and 24 downregulated DEGs were identified. Two specific modules of interest and eight hub genes (ARG1, DEFA4, HP, MMP8, MMP9, MPO, OLFM4, PGLYRP1) were screened out. Functional enrichment analysis suggested that complex neutrophil-related functions play a decisive role in the disease pathogenesis. CIBERSORT indicated neutrophils, M0 macrophages, CD8+ T cells, and naïve B cells to be relevant drivers of disease progression. Additionally, we identified TPM2 and GZMB as potential prognostic markers for treatment response to canakinumab. Moreover, sulindac sulfide, (-)-catechin, and phenanthridinone were identified as promising treatment agents. This study provides a new insight into molecular and cellular pathogenesis of active SJIA and highlights potential targets for further research.
Topics: Arthritis, Juvenile; Child; Computational Biology; Humans; Neutrophils; Prognosis
PubMed: 34480465
DOI: 10.17305/bjbms.2021.6016