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Current Opinion in Rheumatology Jul 2024This review summarizes latest developments in treatment of juvenile spondyloarthritis (JSpA), specifically enthesitis-related arthritis (ERA) and juvenile psoriatic... (Review)
Review
PURPOSE OF REVIEW
This review summarizes latest developments in treatment of juvenile spondyloarthritis (JSpA), specifically enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA).
RECENT FINDINGS
There has been addition of biologic disease modifying antirheumatic drugs (bDMARDs) beyond tumor necrosis factor inhibitors (TNFi) for JSpA such as IL-17 blockers, IL-23 blockers, and janus activating kinase inhibitors with favorable safety profile. Conducting robust clinical trials for this subpopulation of JIA remains a challenge; extrapolation studies are being used to obtain approval from regulatory agencies.
SUMMARY
Newer drug therapies have expanded the scope of treatment for patients with JSpA. bDMARDs such as adalimumab, etanercept, infliximab, and secukinumab have demonstrated clinically significant treatment efficacy in ERA and JPsA. Based on extrapolation studies, intravenous golimumab, etanercept, abatacept, and ustekinumab have gained Food and Drug Administration (FDA) approval for JPsA. Long-term follow-up studies continue to demonstrate acceptable safety profiles. There is need for more real-world data on drug efficacy from Registry studies and research on effective de-escalation strategies.
Topics: Humans; Antirheumatic Agents; Arthritis, Juvenile; Spondylarthritis; Arthritis, Psoriatic; Biological Products; Treatment Outcome; Child
PubMed: 38639758
DOI: 10.1097/BOR.0000000000001016 -
The Journal of Clinical Pediatric... Sep 2023Although periodontal diseases have been widely reported in patients with juvenile idiopathic arthritis (JIA), their association with JIA remains controversial. This... (Meta-Analysis)
Meta-Analysis
Although periodontal diseases have been widely reported in patients with juvenile idiopathic arthritis (JIA), their association with JIA remains controversial. This systematic review and meta-analysis aimed to evaluate the association between JIA and periodontal diseases to facilitate oral health management and periodontal disease prevention in JIA patients. We conducted a comprehensive search of Web of Science, Cochrane Library, PubMed, Embase, Chinese Scientific and Technological Journal (VIP) database, Wan Fang Data, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database (CBM) up to 30 September 2022, without publication dates or language restrictions. Two authors independently evaluated observational studies for inclusion, and the quality of the included studies was assessed using the Newcastle Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ). Continuous variables are presented as mean difference (MD) and 95% confidence interval (CI). Parameters of the simplified oral hygiene index (OHI-S), plaque index (PI), gingival index (GI), clinical attachment loss (CAL), and probing depth (PD) were considered as outcome measures and were compared between JIA patients and healthy controls. The initial search comprised 15 studies with a total of 1537 individuals. The meta-analysis showed the parameters of OHI-S (MD = 0.12, 95% CI: 0.04-0.19, = 0.002), PI (MD = 2.08, 95% CI: 1.67-2.50, < 0.00001), GI (MD = 0.50, 95% CI: 0.17-0.82, = 0.003), CAL (MD = 0.22, 95% CI: 0.01-0.43, = 0.04), and PD (MD = 1.42, 95% CI: 0.08-2.77, = 0.04) in JIA patients were significantly higher than those of healthy controls. All of the included studies were of high quality. This systematic review and meta-analysis showed a possible association between JIA and periodontal diseases. Therefore, it is recommended to continuously pay attention to the periodontal health of JIA patients and fully explore the underlying mechanism.
Topics: United States; Humans; Arthritis, Juvenile; Periodontal Diseases; Administration, Oral; Databases, Factual; Oral Health
PubMed: 37732432
DOI: 10.22514/jocpd.2023.050 -
Revue Medicale Suisse Jan 2024In rheumatology, this year has been characterized by a broader knowledge of the pathogenesis of rheumatoid arthritis and mechanisms involved in the onset and persistence...
In rheumatology, this year has been characterized by a broader knowledge of the pathogenesis of rheumatoid arthritis and mechanisms involved in the onset and persistence of low back pain. Studies relevant to the management of of gout, axial spondyloarthritis, autoinflammatory diseases and systemic vasculitides were published. New data on the safety of JAK inhibitors have been published. The ASAS-EULAR recommendations for the treatment of axial spondyloarthritis were updated, and the 2023 EULAR/PReS guidelines for the diagnosis and treatment of systemic juvenile idiopathic arthritis and adult-onset Still's disease are now available. New molecules and different glucocorticoid sparing strategies were introduced for giant cell arteritis.
Topics: Adult; Humans; Rheumatology; Arthritis, Juvenile; Arthritis, Rheumatoid; Giant Cell Arteritis; Axial Spondyloarthritis
PubMed: 38231111
DOI: 10.53738/REVMED.2024.20.856-7.102 -
Frontiers in Microbiology 2024The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the...
OBJECTIVE
The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators.
METHODS
Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization.
RESULTS
In our MR analysis, a positive correlation was observed between and the risk of juvenile idiopathic arthritis, while showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%].
CONCLUSION
Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.
PubMed: 38605717
DOI: 10.3389/fmicb.2024.1363776 -
Pediatric Rheumatology Online Journal Oct 2023This study aimed to elicit and quantify preferences for treatments for juvenile idiopathic arthritis (JIA).
BACKGROUND
This study aimed to elicit and quantify preferences for treatments for juvenile idiopathic arthritis (JIA).
METHODS
We conducted a discrete-choice experiment among adolescents with JIA in the United States (US) (n = 197) and United Kingdom (UK) (n = 100) and caregivers of children with JIA in the US (n = 207) and UK (n = 200). In a series of questions, respondents chose between experimentally designed profiles for hypothetical JIA treatments that varied in efficacy (symptom control; time until next flare-up), side effects (stomachache, nausea, and vomiting; headaches), mode and frequency of administration, and the need for combination therapy. Using a random-parameters logit model, we estimated preference weights for these attributes, from which we derived their conditional relative importance.
RESULTS
On average, respondents preferred greater symptom control; greater time until the next flare-up; less stomachache, nausea, and vomiting; and fewer headaches. However, adolescents and caregivers in the US were generally indifferent across varying modes and frequencies of administration. UK adolescents and caregivers preferred tablets, syrup, or injections to intravenous infusions. US and UK adolescents were indifferent between treatment with monotherapy or combination therapy; caregivers in the UK preferred treatment with combination therapy to monotherapy. Subgroup analysis showed preference heterogeneity across characteristics including gender, treatment experience, and symptom experience in both adolescents and caregivers.
CONCLUSIONS
Improved symptom control, prolonged time to next flare-up, and avoidance of adverse events such as headache, stomachache, nausea, and vomiting are desirable characteristics of treatment regimens for adolescents with JIA and their caregivers.
Topics: Child; Humans; Adolescent; United States; Arthritis, Juvenile; Caregivers; Headache; Nausea; Vomiting
PubMed: 37865801
DOI: 10.1186/s12969-023-00906-8 -
Orthodontics & Craniofacial Research Dec 2023Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease of childhood. JIA can affect any joint and the temporomandibular joint (TMJ) is one... (Review)
Review
Juvenile idiopathic arthritis (JIA) is the most common inflammatory rheumatic disease of childhood. JIA can affect any joint and the temporomandibular joint (TMJ) is one of the joints most frequently involved. TMJ arthritis impacts mandibular growth and development and can result in skeletal deformity (convex profile and facial asymmetry), and malocclusion. Furthermore, when TMJs are affected, patients may present with pain at joint and masticatory muscles and dysfunction with crepitus and limited jaw movement. This review aims to describe the role of orthodontists in the management of patients with JIA and TMJ involvement. This article is an overview of evidence for the diagnosis and treatment of patients with JIA and TMJ involvement. Screening for the orofacial manifestation of JIA is important for orthodontists to identify TMJ involvement and related dentofacial deformity. The treatment protocol of JIA with TMJ involvement requires an interdisciplinary collaboration including orthopaedic/orthodontic treatment and surgical interventions for the management of growth disturbances. Orthodontists are also involved in the management of orofacial signs and symptoms; behavioural therapy, physiotherapy and occlusal splints are the suggested treatments. Patients with TMJ arthritis require specific expertise from an interdisciplinary team with members knowledgeable in JIA care. Since disorders of mandibular growth often appear during childhood, the orthodontist could be the first clinician to see the patient and can play a crucial role in the diagnosis and management of JIA patients with TMJ involvement.
Topics: Child; Humans; Adolescent; Orthodontists; Temporomandibular Joint; Temporomandibular Joint Disorders; Arthritis, Juvenile; Mandible
PubMed: 37226648
DOI: 10.1111/ocr.12676 -
Pediatric Rheumatology Online Journal May 2024Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause...
BACKGROUND
Juvenile Idiopathic Arthritis (JIA) is a condition that occurs when individuals under the age of 16 develop arthritis that lasts for more than six weeks, and the cause is unknown. The development of JIA may be linked to serum metabolites. Nevertheless, the association between JIA pathogenesis and serum metabolites is unclear, and there are discrepancies in the findings across studies.
METHODS
In this research, the association between JIA in humans and 486 serum metabolites was assessed using genetic variation data and genome-wide association study. The identification of causal relationships was accomplished through the application of univariate Mendelian randomization (MR) analysis. Various statistical methods, including inverse variance weighted and MR-Egger, were applied to achieve this objective. To ensure that the findings from the MR analysis were trustworthy, a number of assessments were carried out. To ensure the accuracy of the obtained results, a range of techniques were utilised including the Cochran Q test, examination of the MR-Egger intercept, implementation of the leave-one-out strategy, and regression analysis of linkage disequilibrium scores. In order to identify the specific metabolic pathways associated with JIA, our primary objective was to perform pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes.
RESULTS
Two-sample summary data MR analyses and sensitivity analyses showed that five metabolites were significantly causally associated with JIA, including two risk factors-kynurenine (odds ratio [OR]: 16.39, 95% confidence interval [CI]: 2.07-129.63, p = 5.11 × 10) and linolenate (OR: 16.48, 95% CI: 1.32-206.22, p = 0.030)-and three protective factors-3-dehydrocarnitine (OR: 0.32, 95% CI: 0.14-0.72, p = 0.007), levulinate (4-oxovalerate) (OR: 0.40, 95% CI: 0.20-0.80, p = 0.010), and X-14,208 (phenylalanylserine) (OR: 0.68, 95% CI: 0.51-0.92, p = 0.010). Furthermore, seven metabolic pathways, including α-linolenic acid metabolism and pantothenate and CoA biosynthesis, are potentially associated with the onset and progression of JIA.
CONCLUSION
Five serum metabolites, including kynurenine and 3-dehydrocarnitine, may be causally associated with JIA. These results provide a theoretical framework for developing effective JIA prevention and screening strategies.
Topics: Humans; Arthritis, Juvenile; Mendelian Randomization Analysis; Genome-Wide Association Study; Child; Polymorphism, Single Nucleotide; Kynurenine
PubMed: 38724970
DOI: 10.1186/s12969-024-00986-0 -
RMD Open Aug 2023Early antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to...
OBJECTIVES
Early antibiotic exposure influences the gut microbiota which is believed to be involved in the pathogenesis of juvenile idiopathic arthritis (JIA). We aimed to investigate the association between systemic antibiotics in prenatal and early life and risk of JIA.
METHODS
We conducted a register-based cohort study including all children born in Norway from 2004 through 2012. The children were followed until 31 December 2020. Main exposures were dispensed antibiotics to the mother during pregnancy and to the child during 0-24 months of age. The outcome was defined by diagnostic codes indicating JIA. Multivariate logistic regression analyses were performed to estimate the association between antibiotic exposure and JIA.
RESULTS
We included 535 294 children and their mothers in the analyses; 1011 cases were identified. We found an association between exposure to systemic antibiotics during 0-24 months and JIA (adjusted OR (aOR) 1.40, 95% CI 1.24 to 1.59), with a stronger association for >1 course (aOR 1.50, 95% CI 1.29 to 1.74) vs 1 course (aOR 1.31, 95% CI 1.13 to 1.53). Subanalyses showed significant associations in all age periods except 0-6 months, and stronger association with sulfonamides/trimethoprim and broad-spectrum antibiotics. There was no association between prenatal antibiotic exposure and JIA.
CONCLUSIONS
The novel observation of no association with prenatal antibiotic exposure and JIA suggests that the association between antibiotics in early life and JIA is unlikely to be confounded by shared family factors. This may indicate that exposure to antibiotics in early life is an independent risk factor for JIA.
Topics: Child; Female; Pregnancy; Humans; Infant, Newborn; Infant; Arthritis, Juvenile; Cohort Studies; Anti-Bacterial Agents; Gastrointestinal Microbiome; Norway
PubMed: 37648397
DOI: 10.1136/rmdopen-2023-003333 -
Paediatric Drugs May 2024Juvenile psoriatic arthritis (JPsA) is a heterogeneous type of non-systemic chronic inflammatory arthritis affecting children and young people. This review focuses on... (Review)
Review
Juvenile psoriatic arthritis (JPsA) is a heterogeneous type of non-systemic chronic inflammatory arthritis affecting children and young people. This review focuses on highlighting challenges in harmonising recommendations for the use of available therapies in JPsA, according to its distinct clinical phenotypes, and explores the similarities and differences between the disease classification and management across age. We further explore the emerging therapeutic landscape, summarising the recently completed clinical trials in JPsA, and ongoing studies in both JPsA and adults with psoriatic arthritis, highlighting unmet needs and barriers for translational research in JPsA. The novel therapeutic agents in clinical development in JPsA range from monoclonal antibodies targeting interleukin (IL)-17, IL-12/23 and IL-23 blockades to synthetic small molecules targeting Janus kinase and tyrosine kinase and phosphodiesterase-4 inhibition. In addition, there are head-to-head clinical trials comparing tumour necrosis factor-α blockade with both IL-17 and IL-23 inhibition. Most of these new therapies have been tested in adults with psoriatic arthritis and have advanced to the phase III stage of drug development or received license for use, suggesting promising signals for efficacy and potentially acceptable safety and tolerability for JPsA. Further translational research in JPsA is required to improve our understanding of the impact of age at onset on treatment efficacy, as well as to provide opportunities for better management of refractory disease and improved long-term outcomes in JPsA, for ultimate patient benefit.
Topics: Humans; Arthritis, Psoriatic; Child; Arthritis, Juvenile; Antirheumatic Agents; Molecular Targeted Therapy; Antibodies, Monoclonal
PubMed: 38310623
DOI: 10.1007/s40272-023-00618-2 -
Arthritis Care & Research Oct 2023Concern exists that medications used to treat patients with systemic juvenile idiopathic arthritis (JIA), particularly interleukin (IL)-1 and IL-6 blocking agents, might...
OBJECTIVE
Concern exists that medications used to treat patients with systemic juvenile idiopathic arthritis (JIA), particularly interleukin (IL)-1 and IL-6 blocking agents, might be causing adverse drug reactions and lung disease (systemic JIA-LD). Carriage of HLA-DRB1*15 has been reported as a risk factor for adverse drug reactions among patients with systemic JIA. We performed a retrospective chart review to evaluate these factors at our center.
METHODS
We reviewed the records of 86 subjects with systemic JIA followed for at least 6 months between 1996 and 2022. HLA typing was performed in 23 of the subjects. We compared characteristics of patients with or without eosinophilia. Among patients with HLA typing, we compared clinical characteristics of subjects with or without DRB1*15 and with or without systemic JIA-LD.
RESULTS
Among the 23 patients with HLA typing, 74% carried DRB1*15, and 63% of patients without systemic JIA-LD carried DRB1*15. Seven subjects had systemic JIA-LD, all of whom carried DRB1*15. Patients with systemic JIA-LD were younger at the time of diagnosis and more likely to have had macrophage activation syndrome. Exposure to IL-1 and IL-6 blockers was common, occurring in 95% of patients. Eosinophilia occurred in 39% of patients with systemic JIA, often before IL-1 or IL-6 blockade. Eosinophilia was associated with adverse drug reactions and macrophage activation syndrome. There was 1 death, unrelated to active systemic JIA disease.
CONCLUSION
Carriage of DRB1*15 was more common in this cohort of patients with systemic JIA than in the general population. Eosinophilia and systemic JIA-LD were more common among patients with severe systemic JIA complicated by macrophage activation syndrome.
Topics: Humans; HLA-DRB1 Chains; Arthritis, Juvenile; Retrospective Studies; Macrophage Activation Syndrome; Interleukin-6; Genetic Predisposition to Disease; Eosinophilia
PubMed: 37052526
DOI: 10.1002/acr.25132