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Rheumatology (Oxford, England) Jun 2024Previous epidemiological data of JIA in Finland are from the turn of the millennium. We aimed to determine the recent annual incidence of JIA in several consecutive...
OBJECTIVE
Previous epidemiological data of JIA in Finland are from the turn of the millennium. We aimed to determine the recent annual incidence of JIA in several consecutive years in Finland and to explore the differences in incidence between sexes, age groups, and regions.
METHODS
We analyzed all children <16 years of age who met the ILAR classification criteria for JIA. Cases from 2000-2020 were identified from two national registers: the Care Register for Health Care of the Finnish Institute for Health and Welfare and the Reimbursement Register containing medication data from the Social Insurance Institution of Finland; cases from 2016-2020 were identified from the Finnish Rheumatology Quality Register.
RESULTS
The incidence of JIA was 31.7 per 100 000 (95% CI 30.2, 33.1), according to the Care Register in 2000-2020 and peaked in 2010-2014. No considerable differences in incidence rates were observed among registers. In all age groups, incidence in girls was predominant compared with boys. The incidence in girls peaked at the ages of 2 years and 14-15 years. Decreasing incidence was observed among boys 0-3 years old during the entire study period, whereas increasing incidence was observed among teenage girls and boys 4-7 years old in 2000-2013.
CONCLUSION
The incidence of JIA is not only very high with respect to that in other parts of the world but also higher than previously reported in Finland. The incidence varied by region and year but was not higher at the end than the beginning of the study period.
PubMed: 38857448
DOI: 10.1093/rheumatology/keae322 -
Ocular Immunology and Inflammation Jun 2024To report a case of presumed fungal infection in a patient with JIA following prolong immunosuppression, and after initiation of adalimumab therapy. Method:...
PURPOSE
To report a case of presumed fungal infection in a patient with JIA following prolong immunosuppression, and after initiation of adalimumab therapy. Method: Retrospective Chart Review.
RESULT
A 20-year-old female, previously diagnosed with JIA, presented with a three-week history of blurred vision in her left eye. She had a long history of treatment with oral corticosteroids, sulfasalazine, and methotrexate, followed by tocilizumab injections and later etanercept. Recently, she was started on adalimumab injections. Fundus examination of the left eye demonstrated multifocal retinitis scattered throughout the fundus. Optical coherence tomography of the lesions showed hyperreflectivity in the inner retina with posterior shadowing and vitreous aggregates extending into the vitreous cavity. After her second adalimumab dose, she experienced blurred vision. Examination of the fundus revealed multifocal retinitis in the left eye, sparing the macula. After stopping immunomodulators and starting empirical antifungal therapy with oral fluconazole, her retinal lesions began to improve. A vitreous biopsy was performed, and intravitreal voriconazole was administered, but microbiological tests were negative. Nevertheless, her retinal lesions resolved almost completely with continued antifungal treatment. By the 6-week follow-up, her retinitis had fully resolved, maintaining excellent visual acuity.
CONCLUSION
This case underscores the need for a high index of suspicion for infection in patients with long-term immunosuppression, highlighting the importance of early therapeutic intervention.
PubMed: 38856750
DOI: 10.1080/09273948.2024.2361355 -
Best Practice & Research. Clinical... Jun 2024Juvenile Idiopathic Arthritis (JIA) is sometimes considered a diagnosis of exclusion as the name signifies that no cause is evident for this form of arthritis. Despite... (Review)
Review
Juvenile Idiopathic Arthritis (JIA) is sometimes considered a diagnosis of exclusion as the name signifies that no cause is evident for this form of arthritis. Despite this JIA has some classical clinical features and many categories are defined based on the phenotype. Since there is no diagnostic test for JIA, diseases that can mimic JIA, including Primary Immunodeficiencies (PID) can sometimes be misdiagnosed as JIA. The clues to suspecting PIDs are early age of onset, presence of family history, increased susceptibility to infections, unusual features like urticaria, interstitial lung disease, sensorineural hearing loss and poor response to conventional therapy, amongst others. This review will highlight the basics of PIDs and will discuss PIDs that can present with arthritis and hence can be confused with JIA.
PubMed: 38851969
DOI: 10.1016/j.berh.2024.101960 -
Annals of the Rheumatic Diseases Jun 2024We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study.
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.
PubMed: 38849152
DOI: 10.1136/ard-2023-225094 -
Acta Paediatrica (Oslo, Norway : 1992) Jun 2024Higher adiposity and increased risk of cardiovascular diseases have been reported in juvenile idiopathic arthritis (JIA), but body composition measurements have produced...
Increased adiposity in juvenile idiopathic arthritis - A comparison of the bioelectrical impedance analysis and dual-energy X-ray absorptiometry for the assessment of body composition.
AIM
Higher adiposity and increased risk of cardiovascular diseases have been reported in juvenile idiopathic arthritis (JIA), but body composition measurements have produced inconsistent results. This controlled cross-sectional study assessed body composition with two methods to evaluate adiposity in children with JIA.
METHODS
We measured body composition by dual- energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) from 79 JIA-patients in two Finish university hospitals in 2017-2019. Their age- and sex-matched controls (n = 79) were selected from the Physical Activity and Nutrition in Children- study and through National Registry.
RESULTS
Body fat percentage measured by BIA was higher (mean, SD) in patients compared to controls (23.1 ± 9.3% vs. 20.1 ± 7.5%, p = 0.047). Also, using DXA, there was a tendency of higher body fat percentage in patients (27.1 ± 9.1% vs. 24.6 ± 8.6, p = 0.106). BIA and DXA showed strong correlation (r from 0.810 to 0.977) in all body composition variables.
CONCLUSION
Increased adiposity was observed in patients with JIA. Evaluation of body composition should be included in the multidisciplinary care of JIA to reduce the possible risk of cardiovascular diseases in adulthood. BIA could be a useful tool for assessing body composition due to its clinical availability and safety.
PubMed: 38847445
DOI: 10.1111/apa.17318 -
Scientific Reports Jun 2024While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the...
While adaptive immune responses have been studied extensively in SLE (systemic lupus erythematosus), there is limited and contradictory evidence regarding the contribution of natural killer (NK) cells to disease pathogenesis. There is even less evidence about the role of NK cells in the more severe phenotype with juvenile-onset (J)SLE. In this study, analysis of the phenotype and function of NK cells in a large cohort of JSLE patients demonstrated that total NK cells, as well as perforin and granzyme A expressing NK cell populations, were significantly diminished in JSLE patients compared to age- and sex-matched healthy controls. The reduction in NK cell frequency was associated with increased disease activity, and transcriptomic analysis of NK populations from active and low disease activity JSLE patients versus healthy controls confirmed that disease activity was the main driver of differential NK cell gene expression. Pathway analysis of differentially expressed genes revealed an upregulation of interferon-α responses and a downregulation of exocytosis in active disease compared to healthy controls. Further gene set enrichment analysis also demonstrated an overrepresentation of the apoptosis pathway in active disease. This points to increased propensity for apoptosis as a potential factor contributing to NK cell deficiency in JSLE.
Topics: Humans; Killer Cells, Natural; Lupus Erythematosus, Systemic; Female; Male; Adolescent; Child; Phenotype; Granzymes; Perforin; Apoptosis; Transcriptome; Gene Expression Profiling; Case-Control Studies
PubMed: 38844784
DOI: 10.1038/s41598-024-62325-3 -
Zeitschrift Fur Rheumatologie Jun 2024Coronavirus disease 2019 (COVID-19) has influenced the world over the last 3 years. Although the risk of a severe course is low in children, it can be influenced by...
Coronavirus disease 2019 (COVID-19) has influenced the world over the last 3 years. Although the risk of a severe course is low in children, it can be influenced by chronic rheumatic diseases or treatment with immunosuppressive drugs or immunomodulatory medication. The German register for biologics in pediatric rheumatology (BIKER) documented systematic data from 68 centers on the occurrence, presentation and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children with rheumatic diseases. Between March 2020 and December 2022, a total of 927 SARS-CoV‑2 infections in 884 patients could be reported and analyzed in pediatric patients with rheumatic diseases. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis (716 infections) followed by genetic autoinflammation (103 infections), systemic autoimmune diseases (78 infections), idiopathic uveitis (25 infections) and vasculitis (5 infections). Only four patients were treated as inpatients. A 3.5-year-old female patient died during the first wave from encephalopathy and respiratory failure. The patient was treated with methotrexate (MTX) and steroids for systemic JIA. Genetic tests revealed a previously unknown congenital immune defect. No other patient had to be ventilated or treated on the intensive care unit. A case of uncomplicated pediatric inflammatory multisystem syndrome (PIMS) was registered in a patient with JIA treated with MTX. At the time of the infection over 60% of the patients were treated with standard disease modifying antirheumatic drugs (DMARD) and/or biologics. Although the patients treated with MTX showed a slightly longer duration of symptoms, the antirheumatic treatment did not appear to have a negative influence on the severity or outcome of the SARS-CoV‑2 infection.
PubMed: 38844689
DOI: 10.1007/s00393-024-01515-w -
The Lancet. Rheumatology Jul 2024For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to...
Outcomes after anti-tumour necrosis factor originator to biosimilar switching in children and young people with juvenile idiopathic arthritis in the UK: a national cohort study.
BACKGROUND
For cost-saving purposes, children and young people with juvenile idiopathic arthritis (JIA) are being switched (for non-medical reasons) from biological originators to biosimilars. Here, we aimed to investigate those who switched from an anti-tumour necrosis factor (TNF) originator to a biosimilar, regarding drug survival and disease activity, compared with a matched cohort who continued the originator.
METHODS
This analysis included all patients in the UK JIA Biologics Register switching directly from an anti-TNF originator to a biosimilar of the same product. All patients were matched (age, sex, disease duration, calendar year of when patients started originator therapy, line of therapy, and International League of Associations for Rheumatology [ILAR] category) to patients continuing the originator. For those matched successfully, a Cox proportional hazard model assessed whether drug persistence differed between those who switched compared with those who continued the originator. Overall change in the 71-joint juvenile arthritis disease activity score and the proportion of patients with a clinically important worsening score (by ≥1·7 units) after 6 months was compared between cohorts. This analysis was designed to address a priority research area set by our patient partners.
FINDINGS
There were 224 children and young people with non-systemic JIA (139 [62%] were female, and 85 [38%] were male) identified as switching from a biological originator to a biosimilar of the same product from Jan 1, 2017, to July 7, 2023. 143 (64%) patients were originally on adalimumab, 56 (25%) on etanercept, and 25 (11%) on infliximab. Of these, 164 patients were matched successfully to those continuing the originator. There was no evidence that patients switching were more likely to stop treatment compared with those continuing the originator, with a hazard ratio of 1·46 (95% CI 0·93-2·30). Of the 51 patients in the biosimilar group who stopped treatment, 18 (35%) switched back to the originator (14 in the first year), 28 (55%) started a different biological drug, and five (10%) discontinued all treatment by the last follow-up. Of the 87 matched patients with available disease activity, there was no evidence that JADAS-71 worsened more after 6 months, with an odds ratio of 0·71 (95% CI 0·34-1·51; p=0·38).
INTERPRETATION
In this matched comparative effectiveness analysis, children and young people with JIA switched from originators to biosimilars. Disease activity was similar between patients switching compared with those continuing the originator. Three quarters of patients were still receiving their biosimilar after 1 year, with switching back to originator uncommon, at only 9% after 1 year, suggesting good tolerability of non-medical switching in this patient population. This information is reassuring to clinicians and patients regarding the effect of non-medical biological switching.
FUNDING
British Society for Rheumatology, Versus Arthritis, and National Institutes for Health Research Manchester Biomedical Research Centre.
Topics: Humans; Arthritis, Juvenile; Male; Female; Biosimilar Pharmaceuticals; Child; Adolescent; Drug Substitution; Antirheumatic Agents; United Kingdom; Cohort Studies; Treatment Outcome; Child, Preschool; Tumor Necrosis Factor-alpha; Infliximab; Adalimumab; Etanercept; Biological Products
PubMed: 38843858
DOI: 10.1016/S2665-9913(24)00087-0 -
Praxis Der Kinderpsychologie Und... Jun 2024The Protective Role of Self-Regulation for HRQOL of Adolescents with a Chronic Physical Health Condition A physical chronic condition comes with many challenges and...
The Protective Role of Self-Regulation for HRQOL of Adolescents with a Chronic Physical Health Condition A physical chronic condition comes with many challenges and negatively impacts the healthrelated quality of life (HRQOL) of those affected. Self-regulation plays an important role in successfully coping with the demands of a chronic condition. In line with a resource-oriented approach, this study aimed to investigate themoderating effect of self-regulation on the relationship between disease severity andHRQOL. For this, 498 adolescents with cystic fibrosis, juvenile idiopathic arthritis, or type-1 diabetes aged of 12-21 years (M= 15.43, SD= 2.07) were recruited through three patient registers. Subjective disease severity, self-regulation (Brief Self-Control- Scale), andHRQOL (DISABKIDSChronicGenericMeasure)were examined at two time points (T₁ and T₂, one year apart). Cross-sectional analysis showed significant effects of subjective disease severity and self-regulation on HRQOL. Prospective analysis, in which HRQOL at T₁ was controlled for, revealed that disease severity only predicted emotion-related HRQOL at T₂; selfregulation emerged as a predictor for HRQOL subscales independence, emotion, inclusion, exclusion, and treatment. A significantmoderation effect of self-regulation was found on the relationship between disease severity and HRQOL emotion. Our results highlight the positive impact of self-regulation on quality of life, specifically in the context of chronic conditions and represent a starting point for prevention and intervention approaches.
PubMed: 38840539
DOI: 10.13109/prkk.2024.73.4.311 -
Frontiers in Immunology 2024Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite...
INTRODUCTION
Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity.
METHODS
A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level.
RESULTS
We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. , , , , , and were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels.
CONCLUSION
These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.
Topics: Humans; Arthritis, Juvenile; Female; Monocytes; Transcriptome; Gene Expression Profiling; Adolescent; Adult; Child; Male; Inflammation
PubMed: 38835762
DOI: 10.3389/fimmu.2024.1400036