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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 -
SAGE Open Medical Case Reports 2024Chronic recurrent multifocal osteomyelitis is a rare auto-inflammatory disease in children, with only a few reports of its association with other inflammatory diseases,...
Chronic recurrent multifocal osteomyelitis is a rare auto-inflammatory disease in children, with only a few reports of its association with other inflammatory diseases, such as systemic juvenile idiopathic arthritis. A 15-year-old boy was admitted due to fever, skin rash, arthritis, and high inflammatory factors and was finally diagnosed with systemic juvenile idiopathic arthritis. After 6 months of recovery from the disease, the patient was referred due to local pain and swelling in the arms and left thigh. In radiography, bone lesions were seen in the shoulders, left humerus, and left femoral diaphysis. A whole-body bone scan showed increased absorption in these areas, which suggested a tumor or osteomyelitis. A biopsy of the bone lesion of the left humerus confirmed sterile osteomyelitis. Although the co-incidence of chronic recurrent multifocal osteomyelitis with systemic juvenile idiopathic arthritis is rare, it should be considered in differential diagnosis.
PubMed: 38835427
DOI: 10.1177/2050313X241257185 -
Pakistan Journal of Medical Sciences 2024JIA is a disease with different immunological characteristics and a complicated genetic foundation. HLA B27 is a risk factor for the development of JIA, and its impact...
BACKGROUND & OBJECTIVES
JIA is a disease with different immunological characteristics and a complicated genetic foundation. HLA B27 is a risk factor for the development of JIA, and its impact on immunopathogenesis of the disease is also an area of interest. To determine whether HLA B27 and immune markers varied between JIA patients and healthy population.
METHODS
This comparative cross-sectional study was conducted at Immunology Department of University of Health sciences (UHS), Lahore from February 2018 till August 2021. A total of (71) JIA patients and (34) healthy controls were enrolled. B cells were enumerated by flowcytometry, ELISA was used for serum cytokines estimation and HLA B27 allele was detected by SPSS polymerase chain reaction.
RESULTS
The HLA B27 allele was significantly more in the control group than in the patient group, suggesting it is a protective allele to prevent JIA. Peripheral blood B cell counts and percentages were significantly lower in the HLA B27 positive group than in the HLA B27 negative group of control population. Serum cytokine levels were not significantly different between the HLA B27 positive and HLA B27 negative allele of the two study populations.
CONCLUSION
In this study B cells are different between the two groups of control population however; serum cytokines are comparable between the study groups. Though, it was indicated that HLA B27 may be a preventive allele in the onset of JIA.
PubMed: 38827853
DOI: 10.12669/pjms.40.5.7915 -
Severe Features of Systemic Juvenile Idiopathic Arthritis in Patients with Congenital Heart Disease.The Journal of Rheumatology Jun 2024To describe the clinical features of patients with congenital heart disease (CHD) who subsequently developed systemic juvenile idiopathic arthritis (sJIA).
OBJECTIVE
To describe the clinical features of patients with congenital heart disease (CHD) who subsequently developed systemic juvenile idiopathic arthritis (sJIA).
METHODS
We conducted a retrospective review of patients diagnosed with CHD and sJIA at our institution. Detailed clinical, laboratory and radiographic data were collected from the medical record and reviewed with each patient's primary medical team.
RESULTS
Five patients with sJIA and CHD were identified. Each child had a unique cardiac anatomy but all of the patients required surgical repair during the first year of life. Four children had thymectomies at the time of cardiac surgery. Classic signs of sJIA such as fever (n=5), rash (n=5), and arthritis (n=4) developed after surgical intervention in all of the patients. The individuals in this cohort displayed risk factors associated with severe sJIA, including disease onset before 2 years of age (n=5), elevated IL-18 levels (n=5), baseline eosinophilia prior to initiation of biologic disease modifying anti-rheumatic drugs (bDMARDs) (n=4), and positivity for HLA-DRB1*15:01 alleles (n=4). Macrophage activation syndrome (MAS) occurred in 3 patients and sJIA-associated lung disease (sJIA-LD) was identified in 4 patients. Two children died from complications of their cardiac and/or pulmonary disease.
CONCLUSION
We identified an association between CHD and severe forms of sJIA. While these findings will need to be confirmed in larger, multi-center cohorts, the results highlight the importance of considering a diagnosis of sJIA in children with CHD and remaining vigilant for complications such as MAS and sJIA-LD.
PubMed: 38825355
DOI: 10.3899/jrheum.2024-0180 -
Clinical and Experimental Rheumatology May 2024To evaluate the effectiveness of the anterior segment optical coherence tomography (AS-OCT) for the screening of anterior uveitis in children diagnosed with juvenile...
OBJECTIVES
To evaluate the effectiveness of the anterior segment optical coherence tomography (AS-OCT) for the screening of anterior uveitis in children diagnosed with juvenile idiopathic arthritis (JIA).
METHODS
A cross-sectional, observational, non-randomised study was conducted in JIA patients younger than 18 years. All patients underwent anterior segment (AS-OCT) and macular OCT.
RESULTS
A total of 300 eyes of 150 patients diagnosed with JIA were included; 74% were females, and mean age was 11.12 ± 3.51 years old (range 4.13-18.60). In the slit-lamp examination, anterior uveitis was diagnosed in 16 eyes. In the AS-OCT, anterior uveitis was suspected in 27 eyes; cells were detected in 27 eyes and retrokeratic precipitates in 5 eyes. Sensitivity was 0.94 and specificity was 0.96, positive predictive value was 0.59 and negative predictive value was 0.99, and Kappa-Cohen index was 0.71.
CONCLUSIONS
AS-OCT could be considered for the screening of anterior segment uveitis in children diagnosed with JIA.
PubMed: 38819950
DOI: 10.55563/clinexprheumatol/t7pn4v -
Frontiers in Endocrinology 2024The causal relationship between juvenile idiopathic arthritis (JIA) and primary ovarian failure (POF) remains uncertain. To elucidate this relationship, we employed a...
BACKGROUND
The causal relationship between juvenile idiopathic arthritis (JIA) and primary ovarian failure (POF) remains uncertain. To elucidate this relationship, we employed a two-sample Mendelian randomization analysis.
METHODS
The single nucleotide polymorphisms (SNPs) associated with JIA were obtained from a previously published genome-wide association study (GWAS), while the pooled data for POF originated from the FinnGen consortium. The study populations consisted exclusively of individuals of European descent. In our Mendelian randomization analysis, we performed inverse-variance weighted analysis, weighted-median analysis, weighted-mode analysis and Mendelian randomization-Egger regression analysis, supplemented by sensitivity analyses to validate the accuracy and robustness of the findings.
RESULTS
The IVW (OR = 1.23, 95% CI 1.06-1.43; P = 0.007) and weighted median (OR = 1.25, 95% CI 1.06-1.47; P = 0.009), along with sensitivity analysis validation, provide compelling evidence of a significant causal association between JIA and POF.
CONCLUSION
The study revealed a significant causal association between genetically predicted JIA and POF, indicating that JIA significantly elevates the risk of developing POF. Therefore, it is recommended to implement screening for premature ovarian failure in women diagnosed with JIA.
Topics: Humans; Mendelian Randomization Analysis; Primary Ovarian Insufficiency; Female; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Arthritis, Juvenile; Cohort Studies; Male; Genetic Predisposition to Disease
PubMed: 38818501
DOI: 10.3389/fendo.2024.1340993 -
BMC Pediatrics May 2024Juvenile idiopathic arthritis (JIA), an autoimmune disease affecting children or adolescents and causing joint or systemic symptoms, reportedly has a negative effect on...
BACKGROUND
Juvenile idiopathic arthritis (JIA), an autoimmune disease affecting children or adolescents and causing joint or systemic symptoms, reportedly has a negative effect on the patients' body height. This study aimed to identify factors attributable to substantially reduced adult height (SRAH) in JIA patients.
METHODS
This single-center retrospective cohort study included patients from 2009 to 2019 in Taiwan. We collected JIA patients aged > 18 years at enrollment with a definite diagnosis and undergoing regular outpatient clinic follow-up or disease remission. Target height difference (THD), defined by adult height minus mid-parental height, was calculated for each patient. The calculation results yielded two groups, of which positive THD was defined as the optimal height (OH group) and those with THD below two standardized deviations as the SRAH group. Descriptive statistics and logistic regression analysis were used to analyze the data.
RESULTS
Of 92 JIA patients, 57 and 12 were in the OH and the SRAH groups. Earlier disease onset, especially before the six-year-old, was noted in the SRAH group (p = 0.026). The distribution of JIA subtypes differed significantly between the two groups (p < 0.001); enthesis-related arthritis was the commonest subtype in the OH group, and systemic JIA was the commonest in the SRAH group. Half of the patients in the SRAH group had an active disease status at enrollment, which was higher than the OH group (50.0% vs. 21.1%, p = 0.066). More patients in the SRAH group had received orthopedic surgery due to JIA (25% vs. 3.5%, p = 0.034). Multiple logistic regression analysis showed that SRAH was independently related to systemic JIA (OR = 37.6, 95%CI 1.2-1210.5; p = 0.041).
CONCLUSION
The subtype of systemic JIA, with its characteristics of early disease onset and active disease status, was the essential factor that significantly impacted adult height.
Topics: Humans; Arthritis, Juvenile; Retrospective Studies; Female; Male; Body Height; Adolescent; Child; Taiwan; Growth Disorders; Risk Factors; Adult; Child, Preschool
PubMed: 38816849
DOI: 10.1186/s12887-024-04855-3 -
The Turkish Journal of Pediatrics May 2024Given the strong genetic background of familial Mediterranean fever (FMF), the frequently reported co-existing diseases in children with FMF should also be investigated...
BACKGROUND
Given the strong genetic background of familial Mediterranean fever (FMF), the frequently reported co-existing diseases in children with FMF should also be investigated in other family members. Therefore, we aimed to examine the medical conditions of first-degree relatives (FDRs) of our pediatric patients with FMF in the present study.
METHODS
Chronic diseases of FDRs of pediatric 449 FMF, 147 juvenile idiopathic arthritis (JIA) patients and 93 healthy controls (HC) were questioned during their routine clinical visits for 9 consecutive months.
RESULTS
A total of 1975 FDRs of 449 FMF, 690 FDRs of 147 JIA patients, and 406 FDRs of 93 HC were included into the study. The most common medical conditions were non-atopic asthma (n=71, 3.6%), type 2 DM (n=14, 2%), and tonsillectomy history (n=12, 2.95%) in the FMF, JIA, and HC groups, respectively. Atopic diseases (FMF vs. JIA: p=0.013; FMF vs. HC: p=0.014), rheumatic diseases (FMF vs. JIA: p=0.030; FMF vs. HC: p=0.017), and surgical histories (FMF vs. JIA: p<0.01; FMF vs. HC: p=0.026), including adenoidectomy, tonsillectomy, and appendectomy, were significantly more common in the FMF group than in other groups.
CONCLUSIONS
Our novel findings may contribute to understanding the hereditary burden of co-existing diseases in children with FMF and encourage further studies involving genetic screenings.
Topics: Humans; Familial Mediterranean Fever; Female; Male; Child; Child, Preschool; Arthritis, Juvenile; Adolescent; Turkey; Case-Control Studies; Family; Adult; Asthma
PubMed: 38814299
DOI: 10.24953/turkjpediatr.2024.4589