Treatment Of Juvenile Idiopathic Arthritis Research Articles

A case of mistaken identity: an enthesitis-related arthritis case report

Juvenile idiopathic arthritis is the most common inflammatory rheumatological condition affecting children. The condition stems from the inability of the immune system to discriminate between self and not-self leading to inappropriate immune reactions against joints. The different subtypes are differentiated by the number of joints involved and the presence or absence of certain exclusion factors. Due to overlapping diagnostic criterion and range of clinical presentation, diagnosis can be a difficult task. Our patient initially presented with joint swelling without pain that was initially diagnosed with traumatic swelling that later was considered to be of an infectious etiology. A biopsy revealed synovitis but current treatment for traumatic and infectious causes continued to fail. Finally, an additional joint showed inflammation leading to additional testing that uncovered that the patient was positive for HLA-B27 as well as a first degree relative with ankylosing spondylitis. This coupled with the inflammatory biopsy findings led to the diagnosis of juvenile idiopathic arthritis. The identification of an HLA-B27 positive patient is important as this population has been shown to have low rates of remission, resistance to certain treatments used for juvenile idiopathic arthritis, specifically DMARDS and corticosteroids which are often first line treatments for juvenile idiopathic arthritis. The HLA-B27 patient population has also been shown to progress to axial involvement and joint destruction leading to earlier need for arthroplasties. As early identification is important in the determination to begin biologic treatments early in the disease course, physician should maintain a clinical suspicion for JIA when dealing with swollen joints in the pediatric population.

Fecal microbiota in children with juvenile idiopathic arthritis treated with methotrexate or etanercept

BackgroundAlterations in the composition of the fecal microbiota in children with juvenile idiopathic arthritis (JIA) have been observed in several studies, but it has not been determined whether the standard treatment for JIA changes the composition or function of the microbiota.The first-line disease-modifying anti-rheumatic drug for treatment of JIA is usually methotrexate, followed or supplemented by anti-tumor necrosis factor alpha drugs, such as etanercept. The aim of this study was to investigate the effects of methotrexate and etanercept treatments on the fecal microbiota and the fecal short-chain fatty acids (SCFAs) in children with JIA.MethodsIn this multicenter study, the composition of fecal microbiota from 45 treatment-naïve children with JIA was compared with that from 29 children treated with methotrexate and 12 children treated with etanercept. We also made pairwise comparisons of 15 children sampled before and during methotrexate treatment and 7 children sampled before and during etanercept treatment.The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha-diversity, community composition, and relative abundances of bacterial taxa were analyzed in all comparisons. Analyses of fecal SCFAs, using a high-performance liquid chromatograph, were performed for the pairwise comparisons.ResultsWe did not find any significant differences in α-diversity or community composition of microbiota. However, principal coordinate analysis indicated a change in community composition in 7 of the 15 paired samples before and during methotrexate and 2 of the 7 paired samples before and during etanercept.Comparisons of the relative abundance of taxa revealed minor differences before and during treatment with methotrexate or etanercept, but they were not significant after correction for multiple analyses, and the unpaired and paired analyses did not show similar changes.There were no significant differences in levels of fecal SCFAs before and during treatment with methotrexate or etanercept.ConclusionsTreatment with methotrexate or etanercept had minor, but no significant or consistent changes either on composition of microbiota or on levels of SCFAs, suggesting that these changes are not related to the therapeutic effects of methotrexate or etanercept.

Approach to switching biologics in juvenile idiopathic arthritis: a real-life experience.

The primary aim of the treatment of juvenile idiopathic arthritis (JIA) is complete remission and minimizing the development of complications. Though biologic agents (BAs) provide better disease control, data related to BA switching patterns in JIA patients are scarce. This study aimed to determine the BA switching patterns in JIA patients. The study included children with JIA that received ≥ 1 BAs. Disease activity was evaluated based on the juvenile arthritis disease activity score 71 (JADAS71). Demographic data, clinical and laboratory findings, BA switching patterns, and the rationales for BA switching were recorded. The study included 177 (82 female and 95 male) JIA patients that received ≥ 1 BAs. Mean age at diagnosis of JIA was 9.1 ± 4.9years. BAs were prescribed a median of 14months (range: 3-66months) after diagnosis. Among the 177 patients, 31 (17.5%) required BA switching a median 10.5months (range: 3-38months) after initiation of the first BA. Among all the BAs that were switched to after administration of the first BA, tocilizumab was the most commonly switched (n = 15). The most common reason for BA switching was inadequate response (n = 29). BAs were switched 2 times in 5 patients and 3 times in 1 patient. When patients that switched BAs 1 time were compared to those that switched 2 and 3 times there were not any differences in terms of JIA types, whereas those that switched 2 and 3 times had a higher active joint count and JADAS71 score after 6months of initiation of the first BA. As some of the JIA patients could not achieve remission despite using the prescribed BA, BA switching was required. Herein, we provide data on both BA switching patterns and requirements, which may improve the management of JIA patients.

Single nucleotide polymorphisms associated with methotrexate-induced nausea in juvenile idiopathic arthritis

BackgroundContext: Methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA). MTX treatment is commonly associated with nausea. Large inter-individual variation exists in the level of MTX-induced nausea, possibly due to genetic factors.Purpose: To investigate whether MTX-induced nausea was associated with single nucleotide polymorphisms (SNPs) in genes encoding MTX-transporter proteins, a MTX metabolizing enzyme and a nausea receptor.FindingsMethods: Children aged ≥9 years treated with MTX for JIA were eligible. MTX-induced nausea was registered by the children’s completion of a nausea diary (min. 7 days) and the parents’ completion of the MTX intolerance severity score (MISS). The selected SNPs were: SLCO1B1 (rs4149056; rs4149081), SLCO1B3 (rs2117032), SLC19A1 (rs1051266), ABCC2 (rs2273697; rs3740066; rs717620), ABCB1 (rs2032582; rs1045642), MTHFR (rs1801131, rs1801133), HTR3A (rs1062613; rs1985242; rs1176713) and HTR3B (rs1176744).Result: Enrolled were 121 JIA patients (82 girls: 39 boys) with a median age of 13.3 years (IQR: 11.3–15.1). The median MTX dose was 9.7 mg/m2/week (IQR: 9.0–10.9). The median MTX treatment duration prior to enrolment was 340 days (IQR: 142–766). The SNP analysis was available for 119 patients. MTX intolerance was associated with the genotype distribution of rs1801133 (MTHFR) (p = 0.02). There was no additive effect of the minor alleles for any of the selected SNPs, nor any significant haplotype associations.ConclusionSummary: MTX-induced nausea may be influenced by genetic polymorphisms in a MTX metabolizing enzyme (rs1801133; MTHFR).Implications: Further analyses involving inclusion of larger cohorts are needed to understand the impact of SNPs on MTX-induced nausea in JIA.

Advancing the treatment of juvenile idiopathic arthritis.

Treatment for juvenile idiopathic arthritis has undergone substantial changes in recent decades. These changes are partly due to the availability of new treatments, mainly biological agents, as well as developments in treatment strategies, including a focus on concepts such as treat-to-target. In addition, the creation of large paediatric research networks has improved patient access to, and design of, clinical trials for rare paediatric diseases. Although these advances have resulted in improvements in care for most patients with juvenile idiopathic arthritis, certain subgroups of patients continue to have a poor prognosis. Further research aims to identify patients in these subgroups early, to personalise their care, improve functional outcomes, and minimise long-term damage and harm. Optimising the duration of therapy for those individuals who require systemic immunosuppression is also of importance. Incorporation of novel biomarkers in combination with validated clinical measures in an effort to predict outcomes and target therapy accordingly is an exciting development.

Response to influenza vaccination in immunocompromised children with rheumatic disease: a prospective cohort study

BackgroundPrevention of illness due to infection by influenza viruses is important for children with rheumatic diseases. Biological disease modifying antirheumatic drugs have become increasingly important in the treatment of juvenile idiopathic arthritis, and combinations of immunosuppressive drugs are used for the treatment of systemic disorders, which increase the risk of secondary immunodeficiency. Therefore, we investigated whether children with rheumatic disease can mount a protective antibody response after influenza immunization.MethodsThe prospective multicentre cohort study was conducted in Denmark during the influenza season 2015–2016. Children with rheumatic disease aged six months to 19 years were eligible. Controls were immunologically healthy children. A blood sample was collected before and after vaccination and analysed by haemagglutination inhibition (HI) assay for the 2015–2016 influenza vaccine-strains. In case of flu-like symptoms the child was tested for influenza. For statistical analyses the patients were grouped according to medical treatment or disease.ResultsA total of 226 patients and 15 controls were enrolled. No differences were found for the increase of antibodies from pre-vaccine to post-vaccine between the groups in our primary analyses: A/Cal H1N1pdm09 (p = 0.28), A/Swi H3N2 (p = 0.15) and B/Phu Yamagata (p = 0.08). Only when combining patients across groups a lower increase in antibodies was found compared to controls. Among all patients the pre-vaccine rates for seroprotection using the HI-titer cut-off ≥ 40 were 93.1–97.0 % for all three strains. For seroprotection using the HI-titer cut-off ≥ 110 the pre-vaccine rates for all patients were 14.9–43.6 % for all three strains and an increase in the proportions of patients being seroprotected after vaccination was found for A/Cal H1N1pdm09 and A/Swi H3N2. None of the children with flu-like symptoms tested positive for the vaccine strains.ConclusionsChildren with rheumatic diseases increase in antibody titres after influenza immunization, however, it remains uncertain whether a protective level is achieved.

Fibrosis indexes in adolescents with juvenile idiopathic arthritis treated with methotrexate

Juvenile idiopathic arthritis is the most common form of arthritis in children and adolescents. Methotrexate is the mainstay of juvenile idiopathic arthritis treatment. Methotrexate is well known to cause serum aminotransferase elevations, and longterm therapy has been linked to the development of fatty liver disease, fibrosis and even cirrhosis. The aim of the study was to assess non-invasive liver fibrosis indexes in adolescents with juvenile idiopathic arthritis treated with methotrexate. Materials and methods: A total of 68 children with juvenile idiopathic arthritis were enrolled in the study. A total of 68 children – 25 boys (36.8%) and 43 girls (63.2%) – were examined. The children were divided into four groups based on the methotrexate cumulative dose. The following data were analysed: total bilirubin and its fractions, cholesterol, β-lipoproteins, aspartate transaminase, alanine aminotransferase. Fibrosis indexes, i.e. APRI, FIB-4 score, AAR, AARPRI, were studied. Results: When studying the dynamics of non-invasive indices, their heterogeneous nature and cumulative dose dependence are determined. Statistically significant changes in fibrosis indexes and biochemical parameters were observed when the children reached cumulative methotrexate doses of 1 g and 3 g. Conclusions: It is possible to monitor carefully liver condition during the whole treatment and conduct a more in-depth examination only if it is necessary. Our data shows that the APRI index (AST to platelet ratio index) is most indicative.

Recent progress in the treatment of non-systemic juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease affecting the joints and other organs that occurs in 1 in 1,000 children in the United States. Given the various categories of JIA, interpretation of the literature can be difficult. In this review, new developments in understanding non-systemic JIA and its treatment will be covered. Recent advances in the journey toward personalized treatment in JIA will be highlighted, including a review of currently available biologic modifiers. Uveitis and the temporomandibular joint will be discussed as particularly challenging treatment issues. Recent guideline updates and literature-guided treatment decisions will be reviewed.

Making Decisions About Stopping Medicines for Well-Controlled Juvenile Idiopathic Arthritis: A Mixed-Methods Study of Patients and Caregivers.

Improved treatments for juvenile idiopathic arthritis (JIA) have increased remission rates. We conducted this study to investigate how patients and caregivers make decisions about stopping medications when JIA is inactive. We performed a mixed-methods study of caregivers and patients affected by JIA, recruited through social media and flyers, and selected by purposive sampling. Participants discussed their experiences with JIA, medications, and decision-making through recorded telephone interviews. Of 44 interviewees, 20 were patients (50% ages <18 years), and 24 were caregivers (50% caring for children ages ≤10 years). We evaluated characteristics associated with high levels of reported concerns about JIA or medicines using Fisher's exact testing. Decisions about stopping medicines were informed by competing risks between disease activity and treatment. Participants who expressed more concerns about JIA were more likely to report disease-related complications (P = 0.002) and more motivated to continue treatment. However, participants expressing more concern about medicines were more likely to report treatment-related complications (P = 0.04) and felt more compelled to stop treatment. Additionally, participants considered how JIA or treatments facilitated or interfered with their sense of normalcy and safety, expressed feelings of guilt and regret about previous or potential adverse events, and reflected on uncertainty and unpredictability of future harms. Decision-making was also informed by trust in rheumatologists and other information sources (e.g., family and online support groups). When deciding whether to stop medicines whenever JIA is inactive, patients and caregivers weigh competing risks between disease activity and treatment. Based on our results, we suggest specific approaches for clinicians to perform shared decision-making regarding stopping medicines for JIA.

Efficacy and Safety of Abatacept, Adalimumab, and Etanercept in Pediatric Patients With Juvenile Idiopathic Arthritis.

The lack of randomized controlled trials comparing biologics for the treatment of juvenile idiopathic arthritis (JIA) has led to wide variation in treatment approaches. The objective of this study is to compare the efficacy and safety of abatacept, adalimumab, and etanercept in JIA patients treated at a tertiary pediatric institution. This was a single-center, retrospective chart review of patients initiated on abatacept, adalimumab, or etanercept from December 1, 2015, to August 31, 2018, at Monroe Carell Jr. Children's Hospital at Vanderbilt (VCH). The primary outcome was the change in the Physician Global Assessment (PGA) score after 4 to 6 months of biologic therapy. Secondary outcomes included change in laboratory markers of JIA disease activity, change in the number of joints with active disease or limitation of motion, reduction in corticosteroid dose, adverse effects, adherence among patients who have their medications filled at the institution's specialty pharmacy, and reason for discontinuation of therapy. A total of 139 patients were included, with a median age of 13 years. Most patients, 80.6%, experienced a reduction in their PGA score after starting biologic therapy. There was not a statistically significant difference among the agents (p = 0.64). Adverse effects were reported in only 26.6% of patients, with the most frequent being injection site reactions or pain (n = 35). Ultimately, 32% of patients discontinued biologic therapy with a lack of efficacy being the most common reason. Abatacept, adalimumab, and etanercept were not significantly different in efficacy and safety for the treatment of JIA at this single institution.

Bilateral 0.19 mg Fluocinolone Acetonide Intravitreal Implant in the Successful Treatment of Juvenile Idiopathic Arthritis-Associated Uveitis and Secondary Macular Oedema: A Case Report and Review of Intravitreal Therapies

IntroductionTreatment of juvenile idiopathic arthritis (JIA)-associated uveitis necessitates the use of long-term corticosteroids or immunosuppressive agents, each of which poses their own significant side effect profile. Initial treatment requires intensive topical glucocorticoids, with a step-up approach employing immunosuppressive agents for those cases with poor response or high-risk complications such as macular oedema. To date, there is minimal evidence to support a specific approach to such complicated subgroups. We present the first case to successfully employ the 0.19 mg fluocinolone acetonide implant (ILUVIEN®, Alimera Sciences, Hampshire, UK) as a novel device for prolonged intravitreal administration of disease-modifying agents for patients with JIA complicated by uveitis.MethodsThis retrospective case report describes a 20-year old woman diagnosed with oligoarticular JIA complicated by chronic uveitis and associated cystoid macular oedema (CMO). Considering factors including the patient’s non-compliance, age, lens status, non-steroid response, and good response to short-term intravitreal steroid therapy, the 0.19 mg fluocinolone acetonide intravitreal implant was deemed an appropriate step-up treatment option.ResultsAt 12-month follow-up, the left eye (OS) showed an improvement in visual acuity to 6/15 − 1 from 6/60 + 1 (0.42 from 0.98 logMAR) (pre-insertion) and a reduction in central retinal thickness (CRT) of 199 μm from 471 μm. The right eye (OD), treated 10 months later, showed an improvement in visual acuity to 6/7.5 from 6/24 − 1 (0.10 from 0.56 LogMAR) and a reduction in CRT of 327 μm 6 months after treatment.ConclusionIn this case, the 0.19 mg fluocinolone acetonide implant provided safe and effective long-term treatment of JIA-associated uveitis and secondary CMO. This potentially offers an alternative approach to complex cases that show good response to short-term corticosteroid use.

JNK Pathway-Associated Phosphatase as a Serum Marker for Disease Activity and Treatment Outcome of Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by arthritis of unknown etiology. JNK pathway-associated phosphatase (JKAP) is reported to be a negative regulator of T-cell activation, but its clinical role in JIA is unknown. This study aimed to investigate the correlation of JKAP with disease activity and treatment response to a tumor necrosis factor (TNF) inhibitor, etanercept (ETN), in JIA patients. Totally, 104 JIA patients (6.9 ± 2.7 years old) and 100 age- and sex-matched healthy controls (HCs) (7.2 ± 2.4 years old) were enrolled, and their serum samples were collected for measuring JKAP by enzyme-linked immunoassay. In JIA patients, after 24-week ETN treatment, clinical response was assessed based on the American College of Rheumatology pediatric criteria (ACRpedi) 50 criteria. Results showed that JKAP levels were significantly lower in JIA patients compared with HCs, and of good value in differentiating JIA patients from HCs. Among JIA patients, higher JKAP levels were associated with lower disease activity indexes, including C-reactive protein, number of joints with active arthritis, physician's global assessment of disease activity, and the present history of disease-modifying antirheumatic drugs; higher baseline JKAP levels were correlated with worse ACRpedi 50 response to ETN at week 24, and was also an independent predictive factor for worse ACRpedi 50 response to ETN. Thus, it may be inappropriate to use ETN for JIA patients with higher JKAP levels. In conclusion, serum JKAP is a potential biomarker for JIA activity and treatment response to a TNF inhibitor.

Recent advances in the treatment of juvenile idiopathic arthritis-associated uveitis.

Juvenile idiopathic arthritis–associated uveitis has an estimated prevalence of 10–20% in patients with juvenile idiopathic arthritis, making it the most common cause of chronic anterior uveitis in children. Prompt treatment is important to prevent development of ocular complications and permanent vision loss. In this review, we will discuss the use of immunosuppression in treatment of juvenile idiopathic arthritis–associated uveitis. This will include the use of conventional immunosuppressants, such as methotrexate, biologic anti-tumor necrosis factor agents, such as adalimumab, as well as other anti-tumor necrosis factor agents, including infliximab and golimumab. In addition, we will discuss medications currently in clinical trials or under consideration for juvenile idiopathic arthritis–associated uveitis, including interleukin-6 inhibitors (tocilizumab) and Janus kinase inhibitors (tofacitinib, baricitinib).

Clinical characteristics and biological treatment of adult patient with juvenile idiopathic arthritis

OBJECTIVE To explore the clinical characteristics and biological treatment of juvenile Idiopathic arthritis (JIA) after adulthood. METHODS Selected 358 patients with previous medical history diagnosed by JIA who were hospitalized in the Department of Rheumatology and Immunology, West China Hospital of Sichuan University from January 1, 2009 to January 1, 2019. Perform retrospective analysis of basic information, clinical symptoms, diagnostic indicators, treatment plans, outpatient follow-up (inpatients require outpatient follow-up treatment) and diagnosis and treatment process of 90 eligible cases included, and observe different ages and different courses of disease. The clinical characteristics of young and middle-aged idiopathic arthritis in adults and the outpatient situation of using biological agents for 6 months. RESULTS According to age, they were divided into ≤26 years old group (42 cases) and >26 years old group (48 cases). Under examination [rheumatoid factor (RF), anti-nuclear antibody (ANA), anti-neutrophil antibody (ANCA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin 6 (IL-6), hemoglobin (HGB), white blood cell count (WBC), human leukocyte antigen-B27 (HLA-B27), complement 3 (C3), etc.], concurrent in terms of symptoms, treatment and prognosis, the ≤26-year-old group was generally lighter than the >26-year-old group; that was, the older the age, the heavier the onset of inflammation and other symptoms, the more complications, the worse the treatment effect, and the worse the prognosis, and there were statistical differences academic significance (P 19 years group (44 cases). In terms of examination (RF, ANA, ANCA, ESR, CRP, IL-1β, IL-6, HGB, HLA-B27, C3, etc.), complications, treatment and prognosis, the course of disease ≤19 years group was compared with the disease course> 19 years group Overall mild; that was, the longer the course of the disease, the more severe the onset of symptoms such as inflammation, the more complications, the worse the treatment effect, and the worse the prognosis, P < 0.05, the difference was statistically significant. After 6 months of outpatient treatment with biological agents, it was found that biological agents could improve some of the patients' clinical symptoms and delay the further development of the disease. Compared with the non-biological agent treatment group (48 cases), the biological agent group (42 cases) benefited, and the difference was statistically significant (P < 0.05). CONCLUSION Through retrospective analysis, this article believes that although adult JIA is diagnosed as connective tissue disease, it has special clinical characteristics with the course of the disease and age. Therefore, it should be recommended to give special attention to JIA patients after adulthood, require regular medical treatment in the adult rheumatology department, according to the corresponding connective tissue disease or JIA diagnosis, and standard treatment; at the same time, pay attention to the history of JIA. In the comparison of biological and non-biological treatment, it is proved that biological treatment can effectively improve some of the clinical symptoms of JIA patients after adulthood. Therefore, it is recommended that biological treatment be used as soon as possible if economic conditions permit to delay the development of the disease.

Knee Acoustic Emissions as a Digital Biomarker of Disease Status in Juvenile Idiopathic Arthritis.

In this paper, we quantify the joint acoustic emissions (JAEs) from the knees of children with juvenile idiopathic arthritis (JIA) and support their use as a novel biomarker of the disease. JIA is the most common rheumatic disease of childhood; it has a highly variable presentation, and few reliable biomarkers which makes diagnosis and personalization of care difficult. The knee is the most commonly affected joint with hallmark synovitis and inflammation that can extend to damage the underlying cartilage and bone. During movement of the knee, internal friction creates JAEs that can be non-invasively measured. We hypothesize that these JAEs contain clinically relevant information that could be used for the diagnosis and personalization of treatment of JIA. In this study, we record and compare the JAEs from 25 patients with JIA−10 of whom were recorded a second time 3–6 months later—and 18 healthy age- and sex-matched controls. We compute signal features from each of those record cycles of flexion/extension and train a logistic regression classification model. The model classified each cycle as having JIA or being healthy with 84.4% accuracy using leave-one-subject-out cross validation (LOSO-CV). When assessing the full JAE recording of a subject (which contained at least 8 cycles of flexion/extension), a majority vote of the cycle labels accurately classified the subjects as having JIA or being healthy 100% of the time. Using the output probabilities of a JIA class as a basis for a joint health score and test it on the follow-up patient recordings. In all 10 of our 6-week follow-up recordings, the score accurately tracked with successful treatment of the condition. Our proposed JAE-based classification model of JIA presents a compelling case for incorporating this novel joint health assessment technique into the clinical work-up and monitoring of JIA.

Joint injection practice variations in pediatric rheumatology \u2013 a global survey and call for action

BackgroundIntraarticular injections (IAI) were first reported in adult rheumatology in the 1950s and subsequently gained acceptance as a safe and efficacious treatment in Juvenile idiopathic arthritis (JIA). IAIs are now widely performed and recommended as the initial or only treatment of oligoarticular JIA and ancillary treatment of actively inflamed joints in other varieties of JIA. However, the performance of the procedure is currently not guided by standardized recommendations, and several practice variations are observed.MethodsThis worldwide survey of pediatric rheumatologists (with 48.5% response from Pediatric Rheumatology International Trials Organization [PRINTO and Pediatric Rheumatology Collaborative Study Group [PRCSG] members) captures the differences in pre-procedural, procedural and post-procedural protocols and practices observed across the globe and asks the necessity of developing consensus in this area of Pediatric Rheumatology.ResultsThis worldwide survey of Pediatric Rheumatologists had a response rate of just under 50% and the views of about 42% who routinely performed the procedure. It captured the differences in IAI protocols and practices observed across the globe. Significant variations in practice were noted in use of Local anesthesia, choice, and dose of therapeutic agent for the intraarticular injection and use of ultrasound to guide injections. While some practice variations may be explained by institutional protocols in different parts of the world, the clinical implications of these are largely unknown and beg the need for further studies.ConclusionsGiven these practice variations, the authors recommend further studies to explore the cost and clinical implications and subsequently work towards developing consensus plans to ensure uniformity in this widely used procedure in Pediatric Rheumatology.

New Medications Are Needed for Children With Juvenile Idiopathic Arthritis.

To document the need for additional Food and Drug Administration (FDA)-approved medications for the treatment of juvenile idiopathic arthritis (JIA). The electronic medical records of JIA patients treated at Cincinnati Children's Hospital Medical Center (CCHMC) and data from JIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry were included in this study. Unmet medication need was defined in 2 ways: (a) the presence of chronically uncontrolled JIA, defined as a physician global assessment of JIA activity ≥3 (on a 0-10 scale, where 0=inactive) OR ≥3 joints with active arthritis OR a patient global assessment of well-being ≥3 (on a 0-10 scale, where 0=very well), despite sequential use of ≥2 biologic disease-modifying antirheumatic drugs (bDMARDs); and (b) the use of ≥1 bDMARD not approved for any JIA category. At CCHMC, 829 of 1,599 JIA patients (52%) were treated with ≥1 bDMARD, and 304 (19%) had been exposed to ≥1 unapproved bDMARD. In the CARRA Registry, 4,766 of 7,379 children (65%) had received ≥1 bDMARD, and 1,122 (15%) had been prescribed ≥1 unapproved bDMARD. Of those children treated with ≥2 bDMARDs for whom complete data were available, 52% (255 of 487) at CCHMC and 45% (527 of 1,159) in the CARRA Registry had chronically uncontrolled JIA despite the use of ≥2 bDMARDs. Despite the availability of bDMARDs currently approved for JIA, there is persistent need for additional therapies to control JIA signs and symptoms. Since FDA approval is critical to ensure access to bDMARDs, the study and licensing of new medications is critical to address the unmet medication need and to further improve JIA outcomes.

Role of Biomarkers in Juvenile Idiopathic Arthritis

The aim of this review was to identify the utility of biomarkers used in the diagnosis and the monitoring and treatment of Juvenile idiopathic arthritis (JIA). JIA is a heterogeneous group of diseases characterized by arthritis of unknown etiology that lasts for at least 6 weeks, with onset before the age of 16 years. Unlike adult rheumatoid arthritis, JIA is a heterogeneous arthritis with different subtypes. The diagnosis of JIA is based on clinical evaluation and often involves ruling out other causes of arthritis. Many biomarkers have been studied or are under development to define the classifications of JIA, assess disease activity, predict disease course, treatment response, or the risk of relapse. The diagnostic and prognostic use of biomarkers in JIA could be applied differently depending on diverse subtypes or individuals. To obtain the best clinical outcomes in JIA, it is important to understand the pathophysiology of each JIA subtype and to select and use appropriate biomarkers. (J Rheum Dis 2020;27:233-240)

Fibroblast growth factor and hepatocyte growth factor in adolescents with juvenile idiopathic arthritis treated with methotrexate

Methotrexate (MTX) is a cornerstone of therapy worldwide for juvenile idiopathic arthritis (JIA). Despite the fact that fibrosis molecular mechanisms as well as MTX elimination and fibrosis indexes were studied a lot there is still not enough information for adolescence.The aim was to study dynamics of molecular-cellular mechanisms activation of fibrotic processes development in the liver in adolescents with juvenile idiopathic arthritis treated with methotrexate by determining the content of fibroblast growth factor and hepatocyte growth factor.Materials and methods: A total of 68 children with juvenile idiopathic arthritis, were enrolled in the study. 25 boys (36.8 %) and 43 girls (63.2 %) were examined. Children were divided into four groups in accordance with cumulative dose (CD) of methotrexate. The following data were analyzed: liver function tests (aspartate aminotransferase (AST) (U/L), alanylaminotransferase (ALT) (U/L)), lactate dehydrogenase (LDH) (U/L), adiponectin (μg / ml), BFGF (pg / ml), HGF (pg / ml), liver fibrosis indexes APRI and FIB-4 Score.Results. Positive effect of JIA treatment with MTX on the liver is noted. When CD MTX reaches 1 and3 grams, liver state studying is needed. When the CD MTX of1 gram is reached, regulatory mechanisms are involved that provoke liver regeneration. When the CD MTX reaches3 grams, the liver condition may deteriorate, which in the future can lead to irreversible processes of liver fibrosis.Conclusions: Thus, it is important to control possible liver disorders in adolescence treated with MTX. Monitoring the processes of liver fibrosis is appropriate at all stages of JIA treatment, but it is most advisable when the MTX cumulative dose is reaching 1 and3 grams

Current Therapeutic Options for the Treatment of Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease and an exclusion diagnosis that includes all forms of arthritis that persists for more than 6 weeks under the age of 16. Although there is not yet a cure for JIA, and recent advances in the therapeutic field have created a more hopeful present and future for the patients. In the past, therapies for JIA have depended on non-steroidal medication, conventional synthetic disease-modifying antirheumatic drugs and corticosteroids. However, over the last decades, the advent of biologic therapies in JIA contributed to the preservation of functional activity, control of pain, avoidance of joint damage, and extra-articular manifestations. Furthermore, over the last years, international institutions, such as the American College of Rheumatology, have released recommendations and guidelines for rheumatologists for optimal JIA management. All the above have revolutionized the treatment of JIA with promising outcomes. To this end, the relevant literature is reviewed and discussed appropriately.