Treatment Of Juvenile Idiopathic Arthritis Research Articles

8. Delivering methotrexate transdermally for treatment of Juvenile Idiopathic Arthritis employing novel PVA-based hydrogel-forming microneedles: In-vitro studies

8. Delivering methotrexate transdermally for treatment of Juvenile Idiopathic Arthritis employing novel PVA-based hydrogel-forming microneedles: In-vitro studies

Clinical Juvenile Arthritis Disease Activity Score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis

ObjectivesTo assess if the Juvenile Arthritis Disease Activity Score (JADAS71) could be used to correctly identify patients with juvenile idiopathic arthritis (JIA) in need of antitumour necrosis factor therapy (anti-TNF)...

Safety of weekly adalimumab in the treatment of juvenile idiopathic arthritis and pediatric chronic uveitis.

Weekly adalimumab dosing is used to treat juvenile idiopathic arthritis (JIA), uveitis, and other pediatric rheumatic diseases, but the safety of such dosing has not previously been studied. A retrospective chart review was conducted to assess the safety of weekly adalimumab. Demographic and clinical data were collected. Basic descriptive analysis was performed to assess for adverse events from weekly adalimumab. Sixty-nine patients at the University of Minnesota or Gillette Children's Hospital were identified as treated with weekly adalimumab. Sixty (87%) were eligible for the chart review. Weekly adalimumab was used most commonly to treat uveitis (28%, 17/60) and rheumatoid factor-negative polyarticular JIA (25%, 15/60). Mean age at the start of weekly dosing was 13.9years. The majority of patients were concurrently treated with a non-steroidal anti-inflammatory drug and methotrexate. Fifty-three (90%) patients continued weekly dosing for greater than 3months. The mean duration of weekly adalimumab was 2years. Throughout the duration of weekly dosing, 24/60 (40%) patients had documented minor infections not requiring antimicrobials and 24/60 (40%) had documented infections requiring antimicrobial treatment. Only three patients (5%) had an infection requiring hospitalization. Two patients (3%) developed autoimmune disease. Laboratory abnormalities and injection site reactions were rare. Weekly adalimumab was used most commonly to treat uveitis and rheumatoid factor-negative polyarticular JIA, and mean duration of weekly dosing was 2years. Serious adverse events were rare.

Are We Right to Consider Mesenchymal Stem Cells to Be a New Perspective for Patients with Juvenile Idiopathic Arthritis?

Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in childhood. Up to 50% of patients are resistant to standard therapy, which includes non-steroid anti-inflammatory drugs, corticosteroids, disease-modifying anti-rheumatic drugs and biologic therapies. Intra-articular injection of mesenchymal stem cells (MSCs) is proposed as a new approach to JIA treatment. MSCs can modulate inflammation via mechanisms of both adaptive and innate immune response. They are able to inhibit T and B cell proliferation, promote regulatory T cells, suppress the maturation of dendritic cells, stimulate macrophage differentiation into M2 phenotype and reduce effectiveness of natural killer cells. They also secrete plethora of soluble factors which influence joint inflammation. Recent clinical studies reviewed in the article provide promising results which may suggest including intra-articular injection of MSCs in therapy of patients with oligoarticular JIA.

Update on the pathogenesis and treatment of juvenile idiopathic arthritis.

To provide an overview of recently published studies on pathogenesis and management of juvenile idiopathic arthritis (JIA). In the past year, the potential role of network analysis in the understanding of the molecular phenotype of individual JIA subgroups has been highlighted. In addition, potential new targets for pharmacologic interventions have been identified through the elucidation of mechanisms that modulate the function of cells involved in the inflammatory process. There is a growing interest for the role of the gut microbiome in disease pathogenesis, which may open the way to future therapeutic manipulations of fecal microbial population. Recent therapeutic studies have provided important information in large patient samples on the effectiveness and toxicity profile of biologic medications used in JIA. Concomitant administration of methotrexate was found to increase the effectiveness of intra-articular corticosteroid therapy in children with oligoarticular JIA. A great deal of work is being conducted to better define the molecular phenotype of the individual subsets of JIA and to identify potential new targets for therapeutic interventions. The results of the ongoing large-scale international data collections will help establish the long-term safety profiles of biologic medications, in particular the risk of malignancy.

Immunogenicity and safety of influenza vaccination in patients with juvenile idiopathic arthritis on biological therapy using the microneutralization assay

BackgroundSeasonal influenza virus vaccination should be considered in all pediatric patients with rheumatic diseases. Few studies have addressed influenza vaccination safety and efficacy in this group. We aim to prospectively evaluate immunogenicity and safety of the trivalent inactivated influenza vaccine including A/H1N1, A/H3N2 and B strains in children with juvenile idiopathic arthritis (JIA) receiving biological therapy.MethodsThirty-five children diagnosed with JIA and 6 healthy siblings were included. Serum samples were collected prior to, 4-8 weeks and one year after vaccination. Microneutralization assays were used to determine neutralizing antibody titers. The type and duration of therapy were analyzed to determine its effect on vaccine response. Clinical data of the participants were collected throughout the study including severe adverse events (SAE) and adverse events following immunization (AEFI).ResultsTwenty-five patients (74.3%) received biological treatment for JIA; anti TNF-α was prescribed in 15, anti IL-1 receptor in 4 and anti IL-6 receptor therapy in 6 children. The seroprotection rate 4-8 weeks after vaccination in the JIA group was 96% for influenza A/(H1N1)pdm and influenza A/H3N2, and 88% for influenza B. No differences were found in GMT, seroprotection and seroconversion rates for the three influenza strains between the control group and patients receiving biological therapy. Furthermore, long-term seroprotection at 12 months after vaccination was similar in patients receiving either biological or non-biological treatments. No SAEs were observed.ConclusionsIn this study, influenza vaccination was safe and immunogenic in children with JIA receiving biological therapy.

How common is remission in juvenile idiopathic arthritis: A systematic review.

ObjectivesThe ideal goal of treatment for juvenile idiopathic arthritis (JIA) is disease remission. However, many sets of remission criteria have been developed and no systematic review of remission in JIA exists.The current systematic review investigated (1) how remission has been defined across JIA clinical cohorts and (2) the frequency of remission overall and within disease categories.MethodsStudies using prospective inception cohorts published after 1972 were selected if they estimated remission in cohorts of ≥50 patients. Articles focusing on specific medical interventions, not defining remission clearly or not reporting disease duration at remission assessment were excluded. Studies were selected from Medline, Embase, PubMed and bibliographies of selected articles. Risks of selection, missing outcome data and outcome reporting biases were assessed.ResultsWithin 17 studies reviewed, 88% had majority female participants and patient disease duration ranged from 0.5 to 17 years. Thirteen sets of criteria for clinically inactive disease and remission were identified. Uptake of Wallace’s preliminary criteria was good in studies recruiting or following patients after their publication (78%).Remission frequencies increased with longer disease duration from 7% within 1.5 years to 47% by 10 years following diagnosis. Patients with persistent oligoarticular and rheumatoid-factor positive polyarticular JIA were most and least likely to achieve remission, respectively.ConclusionsAchievement of remission increased with longer disease duration, but many patients remain in active disease, even in contemporary cohorts. Multiple sets of outcome criteria limited comparability between studies.

Juvenile Idiopathic Arthritis - Changing Times, Changing Terms, Changing Treatments.

1. Susan Shenoi, MBBS, MS* 1. *Department of Pediatrics, Division of Rheumatology, University of Washington School of Medicine & Seattle Children’s Hospital, Seattle, WA * Abbreviations: ALT: : alanine aminotransferase ANA: : antinuclear antibody AST: : aspartate aminotransferase CARRA: : Childhood Arthritis and Rheumatology Research Alliance CBC: : complete blood cell CRP: : C-reactive protein DMARD: : disease-modifying antirheumatic drug ERA: : enthesitis-related arthritis ESR: : erythrocyte sedimentation rate FDA: : Food and Drug Administration HLA: : human leukocyte antigen IAS: : intraarticular corticosteroid injection IL: : interleukin ILAR: : International League of Associations for Rheumatology IV: : intravenous JIA: : juvenile idiopathic arthritis MAS: : macrophage activation syndrome NSAID: : nonsteroidal anti-inflammatory drug PVNS: : pigmented villonodular synovitis RF: : rheumatoid factor SJIA: : systemic juvenile idiopathic arthritis TMJ: : temporomandibular joint TNF: : tumor necrosis factor The management of juvenile idiopathic arthritis (JIA) has changed radically over the last few decades. This article provides an update on identification of JIA, complications of the condition, and common management strategies to help practitioners treat affected children in conjunction with other specialists as part of a multidisciplinary team. After completing this article, readers should be able to: 1. Recognize the clinical findings associated with the various categories of juvenile idiopathic arthritis (JIA). 2. Recognize the laboratory findings associated with the different categories of JIA and its complications. 3. Formulate a differential diagnosis for children with joint pain. 4. Recognize the long-term complications associated with JIA. 5. Plan the appropriate management of JIA while recognizing adverse effects of some therapies. Arthritis is a common cause of disability in childhood. In children, the condition previously was known as juvenile chronic arthritis or juvenile rheumatoid arthritis. Currently, the preferred name for childhood arthritis is juvenile idiopathic arthritis (JIA) because this term denotes the idiopathic or unknown cause of the condition. The exact incidence and prevalence of JIA is unknown and likely varies across the world. The estimated incidence and prevalence of JIA in the United States is approximately 14 per 100,000 children (95% confidence interval: 10–18) and 113 per 100,000 (95% confidence interval: 55–155), respectively. (1) JIA is believed to have a multifactorial etiology, with both genetic and nongenetic (ie, environmental) contributing causes. Due to the paucity of practicing pediatric rheumatologists, pediatricians or family practice physicians often are “on the front line” for initial identification and treatment of JIA. This article focuses on key points for diagnosis and initial evaluation of JIA and provides an overview of treatment. According …

Safety and effectiveness of etanercept for treatment of juvenile idiopathic arthritis: Results from a postmarketing surveillance

Objectives: The objectives of this surveillance were to determine safety and effectiveness of etanercept in patients with juvenile idiopathic arthritis (JIA).Methods: In this postmarketing surveillance, patients aged 5–16 years with active polyarthritis JIA were treated with etanercept at the doses approved in the Japanese package insert. The occurrence and seriousness of adverse events (AEs) were assessed using the Japanese Medical Dictionary for Regulatory Activities version 15.1. Effectiveness was determined as the improvement from baseline in disease activity score in 28 joints (DAS28)–erythrocyte sedimentation rate (ESR), remission, and physician’s assessment of overall improvement. The number of responders was expressed as a percentage. The last observation carried forward method was used to impute missing data.Results: Safety analysis included 102 patients; 22 patients experienced 36 treatment-related AEs, three of which were unexpected. None of the AEs were deemed to need special safety warnings. Effectiveness analysis included 87 patients. At 24 weeks, 29/46 (63.0%) patients demonstrated either good or moderate response in DAS28-4/ESR and treatment was assessed to be markedly effective or effective by physicians in 79/83 (95.2%) patients.Conclusions: These data are consistent with earlier reports showing that etanercept was effective and demonstrated no safety signals in patients with JIA.

Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis

BackgroundAdalimumab, a fully human anti–tumor necrosis factor α monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis.MethodsIn this multicenter, double-blind, randomized, placebo-controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria.ResultsThe prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; P<0.0001 [the prespecified stopping boundary]). Adverse events were reported more frequently in patients receiving adalimumab than in those receiving placebo (10.07 events per patient-year [95% CI, 9.26 to 10.89] vs. 6.51 events per patient-year [95% CI, 5.26 to 7.77]), as were serious adverse events (0.29 events per patient-year [95% CI, 0.15 to 0.43] vs. 0.19 events per patient-year [95% CI, 0.00 to 0.40]).ConclusionsAdalimumab therapy controlled inflammation and was associated with a lower rate of treatment failure than placebo among children and adolescents with active JIA-associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab had a much higher incidence of adverse events and serious adverse events than those who received placebo. (Funded by the NIHR Health Technology Assessment Programme and Arthritis Research UK; SYCAMORE EudraCT number, 2010-021141-41.)

Comparative Outcome of Oral and Subcutaneous Methotrexate Therapy in Children with Juvenile Idiopathic Arthritis

Background &amp; objective: Juvenile idiopathic arthritis (JIA) is the most disabling illness in children. There are number of disease modifying antirheumatic drugs (DMRDS). Methotrexate (MTX) is one of them and for the last two decades has become the cornerstone for the treatment of JIA, because of its efficacy and safety profile. However, debate is still continuing regarding its route of administration (orally or parenteraly) to have wider efficacy and safety. The present study was conducted to compare the outcome of oral and subcutaneous MTX in the treatment of JIA.&#x0D; Materials &amp; Methods: This comparative clinical trial was conducted in Dhaka Shishu Hospital &amp; Bangladesh Institute of Child Health, over a period of 3 years between January 2013 to December 2015. The study initially included 72 children; of them 22 dropped out or did not comply with treatment protocol and hence were excluded from final analysis. Of the remaining children 25 were in Oral and 25 in subcutaneous group. Primary outcome was defined as the percentage of patients reaching ACR Pedi 30 improvement criteria after 6 months of treatment. The ACR Pedi 30 was reached if there was an improvement of ≥30% in at least 3 of 6 core variables, with no worsening of &gt;1 of the remaining variables by ≥30%.&#x0D; Results: The study demonstrated that children with JIA responded well to MTX treatment irrespective of their route of administration, as was evidenced by the achievement of ACR Pedi 30 criteria by majority of the children after 6 months of treatment. However, in terms of core set of variables, subcutaneous route worked better and faster than the oral route. The mean numbers of active joints in the Oral group dropped from 5 at baseline to nearly 2 and &lt; 2 at 3 and 6 months respectively, which in the Subcutaneous groups dropped from 6 at baseline to 2 and &lt; 1 at 3 and 6 months respectively. The average numbers of joints with limited range of motion at baseline in the Oral and Subcutaneous groups were 3 and &gt; 3 which decreased to 1 and &lt; 1 respectively at month 6. Likewise patient/parents’ global assessment of overall wellbeing improved earlier in Subcutaneous group than that in the Oral group (p &lt; 0.001). Physician’s global assessment of disease activity also responded better in the subcutaneous group compared to that in the Oral group (p &lt; 0.001). The C-HAQ disability index in the Oral group reduced insidiously from 1.3 at baseline to 0.4 at 6 months; in contrast the same parameter steeply decreased from 1.5 at baseline to 0.0 at 6 months indicating that Children Health Assessment Questionnaire responded rapidly to Subcutaneous MTX. The ESR in Oral group decreased from 79 at baseline to &lt; 40 at month 3 and to close to 30 mm at month 6, which in the Subcutaneous group decreased from over 70 at baseline to &lt; 30 and &lt; 20 at month 3 and 6 respectively indicating that the decrease being much faster in the latter group.&#x0D; Conclusion: The study concluded that children with JIA responded well to MTX treatment irrespective of their route of administration, as was evidenced by the achievement of ACR Pedi 30 criteria by majority of the children after 6 months of treatment. However, considering the response in terms of core set of variables, it appears that subcutaneous route worked better and faster than the oral route did.&#x0D; Ibrahim Card Med J 2015; 5 (1&amp;2): 27-34

Pilot study comparing the Childhood Arthritis & Rheumatology Research Alliance (CARRA) systemic Juvenile Idiopathic Arthritis Consensus Treatment Plans

ObjectivesTo assess the feasibility of studying the comparative effectiveness of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plans (CTPs) for systemic Juvenile Idiopathic Arthritis (JIA) using an observational registry.MethodsUntreated systemic JIA patients enrolled in the CARRA Registry were begun on one of 4 CTPs chosen by the treating physician and patient/family (glucocorticoid [GC] alone; methotrexate [MTX] ± GC; IL1 inhibitor [IL1i] ± GC; IL6 inhibitor [IL6i] ± GC). The primary outcome of clinical inactive disease (CID) without current GC use was assessed at 9 months. Trial registration: clinicaltrials.gov NCT01697254; first registered 9/28/12 (retrospectively enrolled).ResultsThirty patients were enrolled at 13 sites; eight patients were started on a non-biologic CTP (2 GC, 6 MTX) and 22 patients on a biologic CTP (12 IL1i, 10 IL6i) at disease onset. Demographic and disease features were similar between CTP groups. CTP choice appeared to segregate by site preference. CID off GC was achieved by 37% (11 of 30) including 11/22 (50%) starting a biologic CTP compared to 0/8 starting a non-biologic CTP (p = 0.014). There were four serious adverse events: two infections, one appendicitis and one macrophage activation syndrome.ConclusionsThe CARRA systemic JIA CTP pilot study demonstrated successful implementation of CTPs using the CARRA registry infrastructure. Having demonstrated feasibility, a larger study using CTP response to better determine the relative effectiveness of treatments for new-onset systemic JIA is now underway.

Safety of tocilizumab in the treatment of juvenile idiopathic arthritis

ABSTRACTIntroduction: Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody and IL-6 receptor antagonist, currently approved for the treatment of systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA) in children aged 2 years or older refractory to conventional treatment. The most common adverse events in patients treated with TCZ were infections, especially in the respiratory tract. The most frequent laboratory abnormalities were altered liver function, neutropenia and elevated cholesterol levels.Areas covered: The safety of TCZ in the treatment of children with JIA was determined based on a review of published clinical trials, including two multicenter studies of patients with sJIA and pJIA (the TENDER and CHERISH trials, respectively). The frequency of adverse events (AEs), serious adverse events (SAEs) and deaths reported in these studies was analyzed and discussed.Expert opinion: TCZ was effective and well tolerated in the treatment of severe forms of sJIA and pJIA, and can be considered a treatment of choice for these conditions. The risk of infections and laboratory abnormalities, such as neutropenia, should be constantly monitored. There is still a need for comparative studies of the risks and benefits of biological agents in patients with refractory JIA.

Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The disease is divided into several subgroups, according to demographic characteristics, clinical features, treatment modalities and disease prognosis. Systemic juvenile idiopathic arthritis, which is one of the most frequent disease subtypes, is characterized by recurrent fever and rash. Oligoarticular juvenile idiopathic arthritis, common among young female patients, is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis. Seropositive polyarticular juvenile idiopathic arthritis, an analogue of adult rheumatoid arthritis, is seen in less than 10% of paediatric patients. Seronegative polyarticular juvenile idiopathic arthritis, an entity more specific for childhood, appears with widespread large- and small-joint involvement. Enthesitis-related arthritis is a separate disease subtype, characterized by enthesitis and asymmetric lower-extremity arthritis. This disease subtype represents the childhood form of adult spondyloarthropathies, with human leukocyte antigen-B27 positivity and uveitis but commonly without axial skeleton involvement. Juvenile psoriatic arthritis is characterized by a psoriatic rash, accompanied by arthritis, nail pitting and dactylitis. Disease complications can vary from growth retardation and osteoporosis secondary to treatment and disease activity, to life-threatening macrophage activation syndrome with multi-organ insufficiency. With the advent of new therapeutics over the past 15 years, there has been a marked improvement in juvenile idiopathic arthritis treatment and long-term outcome, without any sequelae. The treatment of juvenile idiopathic arthritis patients involves teamwork, including an experienced paediatric rheumatologist, an ophthalmologist, an orthopaedist, a paediatric psychiatrist and a physiotherapist. The primary goals of treatment are to eliminate active disease, to normalize joint function, to preserve normal growth and to prevent long-term joint damage. Timely and aggressive treatment is important to provide early disease control. The first-line treatment includes disease-modifying anti-rheumatic drugs (methotrexate, sulphasalazine, leflunomide) in combination with corticosteroids, used in different dosages and routes (oral, intravenous, intra-articular). Intra-articular application of steroids seems to be an effective treatment modality, especially in monoarthritis. Biological agents should be added in the treatment of unresponsive patients. Anti-tumour necrosis factor agents (etanercept, infliximab, adalimumab), anti-interleukin-1 agents (anakinra, canakinumab), anti- interleukin-6 agents (tocilizumab) and T-cell regulatory agents (abatacept) have been shown to be safe and effective in childhood patients. Recent studies reported sustained reduction in joint damage with even complete clinical improvement in paediatric patients, compared to previous data.

Sarilumab: First Global Approval.

Sarilumab (Kevzara™) is a fully human IgG1 monoclonal antibody that binds specifically to both soluble and membrane-bound interleukin (IL)-6 receptors (sIL-6Rα and mIL-6Rα) and thereby inhibits IL-6-mediated signalling through these receptors. Subcutaneous sarilumab is approved in Canada for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more biological or non-biological disease-modifying anti-rheumatic drugs. It is under regulatory review for use in rheumatoid arthritis in other countries, including in the EU, USA and Japan. Sarilumab is also under phase II investigation for the treatment of juvenile idiopathic arthritis. This article summarizes the milestones in the development of sarilumab leading to its first global approval for the treatment of rheumatoid arthritis.

Influence of etanercept on leptin and ghrelin secretion in children with juvenile idiopathic arthritis.

ObjectiveTo assess possible changes in leptin and ghrelin secretion due to etanercept in juvenile idiopathic arthritis (JIA).Methods50 patients with JIA and 16 age-matched controls were enrolled into this prospective, cross-sectional study. Serum leptin, total and acyl ghrelin were measured in addition to white blood cell (WBC) and lymphocyte counts.Results25 patients received etanercept and 25 conventional therapies (including methotrexate) for JIA. There was no difference between treatment and control groups in leptin or ghrelin levels and no evidence of a relationship between leptin and ghrelin in patients with JIA. In all children with JIA there was a correlation between leptin and body mass index (BMI). However, compared with children in the conventional treatment group, children in the etanercept group showed a positive correlation between total ghrelin and BMI and those with a low BMI showed a negative correlation between acyl ghrelin and BMI.ConclusionNo differences in leptin and ghrelin concentrations were found when patients with JIA and controls were compared or when patients who received etanercept were compared with those who received conventional treatment for JIA.

Anti-Interleukin-6 Receptor Tocilizumab for Severe Juvenile Idiopathic Arthritis-Associated Uveitis Refractory to Anti-Tumor Necrosis Factor Therapy: A Multicenter Study of Twenty-Five Patients.

To assess the efficacy of tocilizumab (TCZ) for the treatment of juvenile idiopathic arthritis (JIA)-associated uveitis. We conducted a multicenter study of patients with JIA-associated uveitis that was refractory to conventional immunosuppressive drugs and anti-tumor necrosis factor (anti-TNF) agents. We assessed 25 patients (21 female; 47 affected eyes) with a mean ± SD age of 18.5 ± 8.3 years. Uveitis was bilateral in 22 patients. Cystoid macular edema was present in 9 patients. Ocular sequelae found at initiation of TCZ included cataracts (n = 13), glaucoma (n = 7), synechiae (n = 10), band keratopathy (n = 12), maculopathy (n = 9), and amblyopia (n = 5). Before TCZ, patients had received corticosteroids, conventional immunosuppressive drugs, and biologic agents (median 2 [range 1-5]), including adalimumab (n = 24), etanercept (n = 8), infliximab (n = 7), abatacept (n = 6), rituximab (n = 2), anakinra (n = 1), and golimumab (n = 1). Patients received 8 mg/kg TCZ intravenously every 4 weeks in most cases. TCZ yielded rapid and maintained improvement in all ocular parameters. After 6 months of therapy, 79.2% of patients showed improvement in anterior chamber cell numbers, and 88.2% showed improvement after 1 year. Central macular thickness measured by optical coherence tomography in patients with cystoid macular edema decreased from a mean ± SD of 401.7 ± 86.8 μm to 259.1 ± 39.5 μm after 6 months of TCZ (P = 0.012). The best-corrected visual acuity increased from 0.56 ± 0.35 to 0.64 ± 0.32 (P < 0.01). After a median follow-up of 12 months, visual improvement persisted, and complete remission of uveitis was observed in 19 of 25 patients. Significant reduction in the prednisone dosage was also achieved. The main adverse effects were severe autoimmune thrombocytopenia in 1 patient, pneumonia and then autoimmune anemia and thrombocytopenia in 1 patient, and viral conjunctivitis and bullous impetigo in 1 patient. TCZ appears to be a useful therapy for severe refractory JIA-associated uveitis.

DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis

Novel therapeutics are required for improving the management of chronic inflammatory diseases. Aptamers are single-stranded RNA or DNA molecules that have recently shown utility in a clinical setting, as they can specifically neutralize biomedically relevant proteins, particularly cell surface and extracellular proteins. The nuclear chromatin protein DEK is a secreted chemoattractant that is abundant in the synovia of patients with juvenile idiopathic arthritis (JIA). Here, we show that DEK is crucial to the development of arthritis in mouse models, thus making it an appropriate target for aptamer-based therapy. Genetic depletion of DEK or treatment with DEK-targeted aptamers significantly reduces joint inflammation in vivo and greatly impairs the ability of neutrophils to form neutrophil extracellular traps (NETs). DEK is detected in spontaneously forming NETs from JIA patient synovial neutrophils, and DEK-targeted aptamers reduce NET formation. DEK is thus key to joint inflammation, and anti-DEK aptamers hold promise for the treatment of JIA and other types of arthritis.

Musculoskeletal Ultrasound for Diagnosis and Treatment in Juvenile Idiopathic Arthritis

Among users of musculoskeletal ultrasound (MSUS), the benefits of real-time imaging of patients with juvenile idiopathic arthritis (JIA) are widely appreciated. Yet to the larger pediatric rheumatology public, these advantages may be easily overlooked. MSUS enhances the routine clinical examination, allowing for detection of subclinical disease and an accurate determination of the location and extent of disease activity. Ultrasound visualizes synovitis and tenosynovitis, enthesitis, erosions, and cartilage changes, enabling one to monitor the response to treatment and assisting in the determination of remission. MSUS is particularly suited for guidance for intraarticular corticosteroid injections. The ability to review images at the bedside with patients and their caregivers can be reassuring, to both the patient and the practitioner. Understanding of the normal, healthy sonoanatomy, however, can be challenging and remains a topic of ongoing research. The significance of subclinical synovitis (US-detected features of synovitis in the context of clinically healthy joint) remains unclear. As a better understanding of normal/physiologic sonographic appearance of the growing joint emerges, in particular, the presence of Doppler signal in the developing articular space, the predictive value and prognostic significance of subclinical synovitis will become more evident. What constitutes subclinical disease, too, is somewhat controversial as many healthy joints can demonstrate physiologic fluid, and it is unknown how long synovial thickening can remain after active inflammation has been treated. In my experience, sonographic evidence of synovial thickening/proliferation with a high degree of Doppler activity (more than a few areas of intermittent pixilations) should be considered an actively diseased joint and be incorporated in therapeutic decisions. This review aims to provide an evidence-based update on recent advances and insights into the healthy sonoanatomy of children and the use of ultrasound in the assessment and treatment of juvenile idiopathic arthritis disease manifestations.

Early detection and improvement of diagnosis of patients of the rheumatological profile in Kazan

This article presents the first results of the Federal pilot project «Identification of patients and improvement of diagnostics of juvenile idiopathic arthritis», involving pediatricians clinics Kazan. It is shown that this problem is relevant, socially significant and requires further study. Early treatment of patients with juvenile idiopathic arthritis will not only prevent disablement, but also to achieve stable remission of the disease, and early treatment of juvenile idiopathic arthritis (less than 12 months from the date of the onset of the disease) is a proven favorable prognostic factor in reducing disease activity and remission. Given results draws attention to the need for continuity of medical support doctors of various specialties of the specified number of patients.