Treatment Of Juvenile Idiopathic Arthritis Research Articles

Adherence to low-dose methotrexate in children with juvenile idiopathic arthritis using a sensitive methotrexate assay

BackgroundLow-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined.MethodsThis was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy.ResultsPlasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher’s Exact).ConclusionsQuantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy.

Validation of new medication use algorithms as proxies for worsening disease activity in patients with juvenile idiopathic arthritis.

To facilitate claims-based research on populations with juvenile idiopathic arthritis (JIA), we sought to validate an algorithm of new medication use as a proxy for worsening JIA disease activity. Using electronic health record data from three pediatric centers, we defined new JIA medication use as (re)initiation of disease-modifying antirheumatic drugs or glucocorticoids (oral or intra-articular). Data were collected from 201 randomly selected subjects with (101) or without (100) new medication use. We assessed the positive predictive value (PPV) and negative predictive value (NPV) based on a reference standard of documented worsening of JIA disease activity. The algorithm was refined to optimize test characteristics. Overall, the medication-based algorithm had suboptimal performance in representing worsening JIA disease activity (PPV 69.3%, NPV 77.1%). However, algorithm performance improved for definitions specifying longer times after JIA diagnosis (≥1-year post-diagnosis: PPV 82.9%, NPV 80.0%) or after initiation of prior JIA treatment (≥1-year post-treatment: PPV 89.7%, NPV 80.0%). An algorithm for new JIA medication use appears to be a reasonable proxy for worsening JIA disease activity, particularly when specifying new use ≥1 year since initiating a prior JIA medication. This algorithm will be valuable for conducting research on JIA populations within administrative claims databases.

Paediatric Rheumatology Fails to Meet Current Benchmarks, a Call for Health Equity for Children Living with Juvenile Idiopathic Arthritis, Using Digital Health Technologies.

This critical review begins by presenting the history of Juvenile Idiopathic Arthritis (JIA) management. To move the conversation forward in addressing the current shortcomings that exist in the clinical management of children living with JIA, we argue that to date, the advancement of successful treatments for JIA has been historically slow. Factors implicated in this situation include a lack of rigorous research, JIA being considered a rare disease, and JIA's idiopathic and complex pathophysiology. Despite the well-intended legislative changes to increase paediatric research, and the major advancements seen in molecular medicine over the last 30years, globally, paediatric rheumatology services are still failing to meet the current benchmarks of best practice. Provoking questions on how the longstanding health care disparities of poor access and delayed treatment for children living with JIA can be improved, to improve healthcare outcomes. Globally, paediatric rheumatology services are failing to meet the current benchmarks of best practice. Raising awareness of the barriers hindering JIA management is the first step in reducing the current health inequalities experienced by children living with JIA. Action must be taken now, to train and well-equip the paediatric rheumatology interdisciplinary workforce. We propose, a resource-efficient way to improve the quality of care provided could be achieved by embedding digital health into clinical practice, to create an integrative care model between the children, general practice and the paediatric rheumatology team. To improve fragmented service delivery and the coordination of interdisciplinary care, across the healthcare system.

Evaluation of Medication Withdrawal in Patients with Non-systemic Juvenile Idiopathic Arthritis in Japan Using a Web-based Survey.

Although treatments for juvenile idiopathic arthritis (JIA) have seen considerable advancements, there remains a lack of clear guidelines on withdrawing medications. This study aimed to investigate the current strategies for discontinuing non-systemic JIA treatment. A web-based questionnaire was distributed to Pediatric Rheumatology Association of Japan members. According to 126 responses, the most significant factors influencing JIA treatment tapering were the duration of clinically inactive disease, medication toxicity, and a history of arthritis flares. Respondents were often cautious about discontinuing medication if symptoms, e.g., 'morning stiffness' or 'intermittent joint pain', persisted. Among subtypes, oligoarticular JIA was more amenable to treatment tapering, whereas rheumatoid factor-positive polyarticular JIA proved less amenable. Most respondents started medication tapering after a continuous clinical inactive duration exceeding 12 months, and >50% of them required >6 months to achieve treatment discontinuation. Additionally, 40% of respondents consistently underwent imaging before treatment tapering. The relative risks of treatment continuation and withdrawal should be considered, and decisions should be made accordingly. To obtain improved understanding of and more robust evidence for the optimal strategies for safely discontinuing JIA treatment, it is crucial to continue investigations, including long-term outcomes.

Safety and efficacy of biologic immunosuppressive treatment in juvenile idiopathic arthritis associated with inborn errors of immunity.

This study aims to describe clinical features, therapeutic outcomes, and safety profiles in patients affected by juvenile idiopathic arthritis (JIA) and inborn errors of immunity (IEI) treated with biological Disease-modifying antirheumatic drugs (DMARDs). We enrolled three patients who were followed in the Pediatric Rheumatology Unit at Meyer Children's Hospital in Florence; these patients were affected by JIA, according to ILAR criteria, and IEI, according to the IUIS Phenotypical Classification for Human Inborn Errors of Immunity. Among them, two patients had 22q11.2 deletion syndrome (22q11.2DS) and one patient had X-linked agammaglobulinemia (XLA). Case 1: A 6-year and 2-month-old boy was affected by 22q11.2DS, associated with oligoarticular JIA, at the age of 2 years. He was treated with non-steroidal anti-inflammatory drugs (NSAIDs) and methotrexate, along with oral glucocorticoids but with no benefits. Treatment with etanercept allowed him to achieve remission after 10 months. Case 2: A 6-year and 2-month-old girl was affected by 22q11.2DS, associated with oligoarticular JIA, at the age of 3 years and 11 months. She was treated with NSAIDs, joint injections, and methotrexate but without clinical response. Treatment with Adalimumab allowed her to achieve remission after 6 months. Case 3: A 12-year and 2-month-old boy was affected by XLA, associated with polyarticular JIA, at the age of 9 years and 11 months. He was treated with NSAIDs, methotrexate, joint injections, and oral glucocorticoids with no benefits. He failed to respond to anti-TNF-alpha, tocilizumab, and abatacept. Currently, he is undergoing therapy with sirolimus plus abatacept, which allowed him to achieve remission after 4 months. Results suggest that the use of immunosuppressive biological therapies can control disease activity in these patients. No adverse drug-related reactions were observed during the follow-up.

Treatment of non-systemic juvenile idiopathic arthritis.

In the past two decades, the treatment of juvenile idiopathic arthritis (JIA) has evolved markedly, owing to the availability of a growing number of novel, potent and relatively safe therapeutic agents and the shift of management strategies towards early achievement of disease remission. However, JIA encompasses a heterogeneous group of diseases that require distinct treatment approaches. Furthermore, some old drugs, such as methotrexate, sulfasalazine and intraarticular glucocorticoids, still maintain an important therapeutic role. In the past 5 years, information on the efficacy and safety of drug therapies for JIA has been further enriched through the accomplishment of several randomized controlled trials of newer biologic and synthetic targeted DMARDs. In addition, a more rational therapeutic approach has been fostered by the promulgation of therapeutic recommendations and guidelines. A multinational collaborative effort has led to the development of the recommendations for the treat-to-target strategy in JIA. There is currently increasing interest in establishing the optimal time and modality for discontinuation of treatment in children with JIA who achieve sustained clinical remission. The aim of this Review is to summarize the current evidence and discuss the therapeutic approaches to the management of non-systemic phenotypes of JIA, including oligoarthritis, polyarthritis, enthesitis-related arthritis and psoriatic arthritis.

Specific Features of Juvenile Idiopathic Arthritis Patients' Cytokine Profile.

Juvenile idiopathic arthritis (JIA) is a systemic autoimmune disease that affects the joints, leading to disability. Cytokines and signaling molecules expressed by the immune system cells play a key role in JIA pathogenesis. Understanding how their content changes during pathology development can open up new opportunities for its diagnosis and treatment. The blood plasma of 30 patients with JIA (14 males and 16 females with a mean age of 12.2 ± 4.1) and 20 relatively healthy individuals (10 males and 10 females with a mean age of 10.20 ± 5.85) was analyzed to determine the levels of cytokines using the MILLIPLEX® kit. An increase in interleukins (IL)-1α, 1β, 2, 4, 5, 6, 7, 8, 9, 10, 13, 15, 17F, 22, and 27 and a decrease in IL-3 levels have been shown in patients with JIA. Levels of cytokines, which are important for B-cell activation and proliferation, are increased, while levels of T-cell activating factors remained similar to the control group. Based on our results, it can be assumed that the use of combination therapy aimed at inhibiting both nonspecific interleukins and cytokines that activate B-cells will be more effective for the treatment of JIA.

Towards stratified treatment of JIA: machine learning identifies subtypes in response to methotrexate from four UK cohorts

Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures. Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year. Clusters of MTX 'response' were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment. The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65-0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns. Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis of a stratified medicine programme in early JIA. Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and the National Institute for Health Research.

ВЛИЯНИЕ ПРИМЕНЕНИЯ МЕТОТРЕКСАТА НА СОСТОЯНИЕ МИЕЛОПОЭЗА И ТРОМБОЦИТОПОЭЗА У ДЕТЕЙ С ИДИОПАТИЧЕСКИМ АРТРИТОМ

Methotrexate is the mainstay drug in the treatment of juvenile idiopathic arthritis (JIA). The effect of methotrexate on the hematopoietic system manifests itself in the form of its inhibition, contributing to the development of aplastic anemia, leukopenia, neutropenia and thrombocytopenia. The purpose of the study was to study the effect of methotrexate on the state of the leukocyte and megakaryocyte pool of cells in patients with JIA. Material and methods. The study was carried out on the basis of the 2nd City Children's Clinical Hospital in Minsk. A study of the state of hematopoiesis was carried out in 82 children with JIA who received only methotrexate. The comparison group consisted of 40 patients who were diagnosed with JIA and had a complete blood count performed before starting methotrexate therapy. Results. Statistically significant differences were identified in both the megakaryocyte and leukocyte series. Against the background of an increase in the number of platelets before the start of basic therapy, there was a decrease in the average volume of platelets (p<0.01) and, accordingly, the distribution of platelets by volume (p<0.001). Changes in the white blood cell count (WBC) were manifested in a gradual decrease in the number of leukocytes during long-term use of methotrexate (p < 0.001). Conclusion. The use of methotrexate in patients with JIA contributes to a significant decrease in the content of platelets, leukocytes, neutrophils, lymphocytes, and monocytes, which is due to the relief of the inflammatory process. The duration of methotrexate administration did not affect the content of lymphocytes and basophils.

Assessment of quality of life and physical activity in patients with oligoarticular juvenile idiopathic arthritis in remission.

The purpose of this study was to evaluate physical activity (PA) and health-related quality of life (HRQOL) in children with oligoarticular juvenile idiopathic arthritis (JIA) in remission in comparison with healthy peers and to determine the disease-related factors affecting PA levels. This study was conducted with 50 oligoarticular JIA patients in remission and 50 healthy peers between 9 and 14years. Demographic and clinical characteristics, laboratory parameters, and treatments were noted from electronic medical records. HRQOL was assessed with the Pediatric Quality of Life Inventory (PedsQL). PA was evaluated with the Physical Activity Questionnaire for Children (PAQ-C). Oligoarticular JIA patients had significantly lower self-reported median PedsQL scores in the domains of school functioning and social functioning compared to the control group (67.5 (10) vs. 75 (25), p = 0.001 and 70 (15) vs. 85 (26.3), p < 0.001, respectively). The median PAQ-C score was 2.6 (1.1) in patients with JIA and 3 (0.9) in their healthy peers (p = 0.02). The PAQ-C score was 2.8 (1.2) in patients < 8years at the disease onset and 2.3 (1) in those aged ≥ 8years (p = 0.022). There was no significant difference in the number of affected joints, type of affected joint, MTX and biologic agent treatment, and remission with or without drugs with the total score of the PedsQL and PAQ-C. All PedsQL domains were positively correlated with the PAQ-C. Conclusion: Oligoarticular JIA patients demonstrated lower PA and HRQOL scores compared to healthy controls despite favorable disease control. What is Known: • Oligoarticular JIA has fewer functional limitations and disabilities compared to other JIA subtypes. • As JIA can affect all aspects of a child's life, there is a need to improve the quality of life related to the disease. What is New: • It should be considered that patients with oligoarticular JIA may show lower PA and HRQOL scores compared to healthy controls despite favorable disease control. • Since there may be a relationship between PA and HRQOL, factors that may affect PA should be investigated to provide a holistic approach to JIA treatment.

Diagnostic and prognostic role of synovial tissue analysis in juvenile idiopathic arthritis: a monocentric study

ObjectivesThis study investigates the diagnostic role of synovial tissue analysis in children presenting with arthritis and assesses its prognostic significance to predict clinical outcome in juvenile idiopathic arthritis (JIA).MethodsSynovial samples...

Adolescent and caregiver preferences for juvenile idiopathic arthritis treatment: a discrete-choice experiment

BackgroundThis study aimed to elicit and quantify preferences for treatments for juvenile idiopathic arthritis (JIA).MethodsWe 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.ResultsOn 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.ConclusionsImproved 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.

Comparison of biologic monotherapy versus biologic and disease-modifying anti-rheumatic drug combination in the treatment of non-systemic juvenile idiopathic arthritis

Purpose To explore the efficacy of biologics as mono- or combination therapy with conventional disease modifying anti-rheumatic drugs (cDMARDs) in the treatment of juvenile idiopathic arthritis (JIA). Material and Methods Medical records of patients with JIA followed-up from January 2020 to 2023 who were treated either with biologic drugs as monotherapy or with combination of cDMARD were reviewed retrospectively. Data of demographic features, clinical scores and treatments were assessed. Results Two hundred five cases received etanercept, adalimumab, or tocilizumab alone or in combination with a cDMARD for JIA were included. The male to female ratio of the cohort was almost equal. Oligoarticular was the most common subtype of JIA. Majority (n=128, 62.4%) of the group received biologic drugs as monotherapy, while the remaining third (n=77, 37.6%) used a combination of biologic and a cDMARD. Nearly half of the group (57.1%) were treated with etanercept and etanercept monotherapy was the most commonly used one among all JIA subtypes except juvenile psoriatic arthritis. Adalimumab combination therapy was prescribed in most of the children with juvenile psoriatic arthritis. Adalimumab, alone or in combination with methotrexate, was preferred for all 8 patients with uveitis at the onset of the disease. Adalimumab combined (n=9) and tocilizumab monotherapy (n=4) were the most common biologics in those who developed uveitis during follow-up. Conclusion Etanercept, adalimumab, or tocilizumab are effective and safe biologics in treatment of JIA. Considering their cost-effective properties, choosing biologic drugs timely as combined or monotherapy is effective in preventing early and late sequelae of JIA.

E09 Juvenile idiopathic athritis: a desk review of the available standard treatment guidelines in East Africa

Abstract Background Juvenile Idiopathic Arthritis (JIA) is a common rheumatic disorder in children, with an estimated prevalence of 1 out of every 1000 children worldwide. In Tanzania, a retrospective review of pediatric patients with pediatric rheumatology conditions for seven years, reported JIA as the most prevalent condition. Timely initiation of therapy and availability of appropriate pharmacotherapy halts morbidity and mortality. Treatment guidelines for this condition is a key in guiding appropriate management. Aim This review was conducted to determine the availability of treatment guidelines for JIA in East Africa and compare them with the international guidelines. Methodology This was a desk review of available treatment guidelines for juvenile idiopathic arthritis in East Africa and as well international guidelines for comparison. The search was done on google, google scholar, Medline, HINARI and PubMed. The international guidelines were obtained from the respective webpages of the academic associations for rheumatology disorders. The search words entered in the data bases included ‘JIA treatment guidelines’, ‘Systemic arthritis treatment guidelines’, and ‘treatment guidelines for pediatric arthritis’. Each of the words was entered in the search engine with the names of the East African countries separately. Results There are no available standard guidelines for treatment of juvenile idiopathic arthritis in East Africa. However, available experts contextualize the international guidelines to attend local patients. This happens amidst a region with scarce resources. In a few available studies including ones conducted by A. Migowa et al. and M. Kamau et al. treatment includes use of NSAIDS for pain management, and corticosteroids for treatment bridging until Disease Modifying Anti-Rheumatic Drugs (DMARDS) become effective. Availability of biologics is not consistent in all the hospitals and their access is limited in third world countries (M. Kamau et al.). The reliable Disease Modifying Anti-Rheumatic Drugs of choice remain to be the convectional ones. The international guidelines exist for other regions including Europe (EULAR), America (ACR), and Asia pacific regions (APLAR). Conclusion There is a need to develop standard treatment guidelines in our settings in order to guide clinicians to best manage patients with JIA with the available treatment options in our setting.

Immune Cell-Related Genes in Juvenile Idiopathic Arthritis Identified Using Transcriptomic and Single-Cell Sequencing Data.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. The heterogeneity of the disease can be investigated via single-cell RNA sequencing (scRNA-seq) for its gap in the literature. Firstly, five types of immune cells (plasma cells, naive CD4 T cells, memory-activated CD4 T cells, eosinophils, and neutrophils) were significantly different between normal control (NC) and JIA samples. WGCNA was performed to identify genes that exhibited the highest correlation to differential immune cells. Then, 168 differentially expressed immune cell-related genes (DE-ICRGs) were identified by overlapping 13,706 genes identified by WGCNA and 286 differentially expressed genes (DEGs) between JIA and NC specimens. Next, four key genes, namely SOCS3, JUN, CLEC4C, and NFKBIA, were identified by a protein-protein interaction (PPI) network and three machine learning algorithms. The results of functional enrichment revealed that SOCS3, JUN, and NFKBIA were all associated with hallmark TNF-α signaling via NF-κB. In addition, cells in JIA samples were clustered into four groups (B cell, monocyte, NK cell, and T cell groups) by single-cell data analysis. CLEC4C and JUN exhibited the highest level of expression in B cells; NFKBIA and SOCS3 exhibited the highest level of expression in monocytes. Finally, real-time quantitative PCR (RT-qPCR) revealed that the expression of three key genes was consistent with that determined by differential analysis. Our study revealed four key genes with prognostic value for JIA. Our findings could have potential implications for JIA treatment and investigation.

Surgical Treatment of Juvenile Idiopathic Arthritis in the Era of Novel Drug Therapies.

Juvenile idiopathic arthritis is the most common chronic rheumatic disease encountered in children under the age of sixteen and causes significant impairments in daily life. Over the last two decades, the introduction of new drug treatments (including disease-modifying antirheumatic drugs and biologics) has changed the course of this disease, thus reducing the indication for surgery. However, some patients fail to respond to drug therapy and thus require personalized surgical management, e.g., the local reduction of joint effusion or a synovial pannus (via intra-articular corticosteroid injections, synovectomy, or soft tissue release), and management of the sequelae of arthritis (such as growth disorders and joint degeneration). Here, we provide an overview of the surgical indications and outcomes of the following interventions: intra-articular corticosteroid injections, synovectomy, soft tissue release, surgery for growth disorders, and arthroplasty.

Clonally expanded PD-1-expressing T cells are enriched in synovial fluid of juvenile idiopathic arthritis patients.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic condition in childhood. The disease etiology remains largely unknown; however, a key role in JIA pathogenesis is surely mediated by T cells. T-lymphocytes activity is controlled via signals, known as immune checkpoints. Delivering an inhibitory signal or blocking a stimulatory signal to achieve immune suppression is critical in autoimmune diseases. However, the role of immune checkpoints in chronic inflammation and autoimmunity must still be deciphered. In this study, we investigated at the single-cell level the feature of T cells in JIA chronic inflammation, both at the transcriptome level via single-cell RNA sequencing and at the protein level by flow cytometry. We found that despite the heterogeneity in the composition of synovial CD4+ and CD8+ T cells, those characterized by PD-1 expression were clonally expanded tissue-resident memory (Trm)-like cells and displayed the highest proinflammatory capacity, suggesting their active contribution in sustaining chronic inflammation in situ. Our data support the concept that novel therapeutic strategies targeting PD-1 may be effective in the treatment of JIA. With this approach, it may become possible to target overactive T cells regardless of their cytokine production profile.

Systemic juvenile idiopathic arthritis in the pediatric practice of Donetsk region

Juvenile idiopathic arthritis with systemic onset is a special, rare and the most severe variant of juvenile idiopathic arthritis. The article analyzes the clinical features of the onset and course of juvenile idiopathic arthritis with systemic onset in children living in the ecologically disadvantaged Donetsk region and the efficacy of therapy. Clinical cases are described. According to its clinical manifestations, the systemic variant of juvenile idiopathic arthritis is characterized by the severity of the general inflammatory response, a bright clinical picture, severe damage to internal organs, the development of polyserositis, can lead to the development of life-threatening conditions, such as macrophage activation syndrome, and also leads to the formation of deforming arthritis with early disability of the sick child. The relevance of studying the problem of juvenile idiopathic arthritis with a systemic onset is related to the late diagnosis of the disease, because at the onset of the disease there may be no joint syndrome, and therefore it is impossible to use the criteria of the International League of Rheumatology Associations to verify the diagnosis, which leads to diagnostic errors. Nonsteroidal anti-inflammatory drugs, glucocorticosteroids, and immunosuppressants are used for treatment. The prescription of genetic engineering biological therapy, the choice of the drug, is carried out according to the recommendations of the American College of Rheumatology, depending on the preference for systemic or joint manifestations of the disease. But the question of the optimal approach to regimens of dose reduction, duration of biological therapy, and rules for its withdrawal remains open. Until now, the optimal approach to the treatment of juvenile idiopathic arthritis with a systemic onset is unknown. To date, the issue of treatment in patients with pharmacoresistant variants and persistent course of the disease has not been solved. Therefore, further in-depth study of this problem, optimization of the diagnostic algorithm and an individual approach to therapy are needed.

Chinese clinical practice guidelines for the diagnosis and treatment of juvenile idiopathic arthritis (2023 edition)

幼年特发性关节炎（JIA）是儿童时期常见的慢性风湿性疾病，严重威胁着儿童的健康成长，早期诊断、规范治疗与有效管理是疾病诊治的关键。本指南针对非全身型JIA的相关诊断与评估、治疗原则与目标、常见并发症处理等重要临床问题开展研究证据检索，并形成科学意见推荐，以规范医师在JIA临床诊治实践中的行为，改善患儿远期预后，减轻家庭及社会疾病负担。.

The clinical and experimental treatment of Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and comprises of multiple subtypes. The most relevant disease subtypes, grouped upon current insight in disease mechanisms, are nonsystemic (oligo- and polyarticular) JIA and systemic JIA (sJIA). In this review, we summarize some of the main proposed mechanisms of disease in both nonsystemic and sJIA and discuss how current therapeutic modalities target some of the pathogenic immune pathways. Chronic inflammation in nonsystemic JIA is the result of a complex interplay between effector and regulatory immune cell subsets, with adaptive immune cells, specifically T-cell subsets and antigen-presenting cells, in a central role. There is, however, also innate immune cell contribution. SJIA is nowadays recognized as an acquired chronic inflammatory disorder with striking autoinflammatory features in the first phase of the disease. Some sJIA patients develop a refractory disease course, with indications for involvement of adaptive immune pathways as well. Currently, therapeutic strategies are directed at suppressing effector mechanisms in both non-systemic and sJIA. These strategies are often not yet optimally tuned nor timed to the known active mechanisms of disease in individual patients in both non-systemic and sJIA. We discuss current treatment strategies in JIA, specifically the 'Step-up' and 'Treat to Target approach' and explore how increased insight into the biology of disease may translate into future more targeted strategies for this chronic inflammatory disease at relevant time points: preclinical disease, active disease, and clinically inactive disease.