Management Of Juvenile Idiopathic Arthritis Research Articles

Biomarkers of Response to Biologic Therapy in Juvenile Idiopathic Arthritis.

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthritis of childhood, characterized by various clinical phenotypes associated with variable prognosis. Significant progress has been achieved with the use of biologic treatments, which specifically block pro-inflammatory molecules involved in the disease pathogenesis. The most commonly used biologics in JIA are monoclonal antibodies and recombinant proteins targeting interleukins 1 (IL-1) and 6 (IL-6), and tumor necrosis factor α (TNF-α). Several biomarkers have been investigated in JIA. Aims: To assess the level of evidence available regarding the role of biomarkers in JIA related to guiding clinical and therapeutic decisions, providing disease prognostic information, facilitating disease activity monitoring and assessing biologic treatment response in JIA, as well as propose new strategies for biologic therapy-related biomarker use in JIA. Methods: We searched PubMed for relevant literature using predefined key words corresponding to several categories of biomarkers to assess their role in predicting and assessing biologic treatment response and clinical remission in JIA. Results: We reviewed serological, cellular, genetic, transcriptomic and imaging biomarkers, to identify candidates that are both well-established and widely used, as well as newly investigated in JIA on biologic therapy. We evaluated their role in management of JIA as well as identified the unmet needs for new biomarker discovery and better clinical applications. Conclusion: Although there are no ideal biomarkers in JIA, we identified serological biomarkers with potential clinical utility. We propose strategies of combining biomarkers of response to biologics in JIA, as well as routine implementation of clinically acceptable imaging biomarkers for improved disease assessment performance.

The new role of musculoskeletal ultrasound in the treat-to-target management of juvenile idiopathic arthritis.

This article reviews the role of musculoskeletal ultrasound (MSUS) for the diagnosis, monitoring and treat-to-target management of JIA. Technological advancements in MSUS allow more precise evaluation of arthritis, tenosynovitis and enthesitis versus clinical examination alone, which may assist treatment decisions. In adult studies, serum and synovial biomarkers have correlated with MSUS findings. Within paediatric rheumatology, significant developments in the definition of normal and pathology, a necessity for the future integration of MSUS into treat-to-target management, have already been reached or are underway, which in turn could allow tighter control of disease activity and earlier identification of treatment response and failure, bringing the goal of 'precision medicine' closer. Additionally, the utility of MSUS for the evaluation of subclinical disease remains an unexamined area of interest. 'Ultrasound remission' combined with clinical assessment and immunological markers could therefore potentially improve the treat-to-target management of JIA.

Beyond the guidelines management of juvenile idiopathic arthritis: a case report of a girl with polyarticular disease refractory to multiple treatment options and Leri Weill syndrome

BackgroundThe last two decades brought new treatment options and high quality guidelines into the paediatric rheumatologic practice. Nevertheless, a number of patients still present a diagnostic and therapeutic challenge due to combination of vague symptoms and unresponsiveness to available treatment modalities.Case presentationWe report a case of sixteen years old girl suffering from polyarticular type of juvenile idiopathic arthritis refractory to multiple treatment options. She first presented at the age of 4 with swelling and contractures of both knees. Her symptoms were initially unresponsive to nonsteroidal anti-inflammatory drugs and progressed despite treatment with intraarticular and systemic glucocorticoids and methotrexate. Throughout the years, she received several biologics together with continuous administration of nonsteroidal anti-inflammatory drugs and disease modifying anti-rheumatic drugs as well as intraarticular and systemic glucocorticoids in disease flares. However, none of this options provided a permanent remission, so various other modalities, as well as other possible diagnoses were constantly being considered. Eventually she became dependent on a daily dose of systemic glucocorticoids. In 2018, the treatment with Janus kinase inhibitor tofacitinib was initiated, which led to gradual amelioration of musculoskeletal symptoms, improvement of inflammatory markers and overall well-being, as well as to the weaning of systemic glucocorticoids. As the swelling of the wrists subsided for the first time in many years, Madelung’s deformity was noticed, first clinically, and later radiographically as well. Genetic analysis revealed short-stature homeobox gene deficiency and confirmed the diagnosis of Leri Weill syndrome.ConclusionsThis case report emphasizes the need for reporting refractory, complicated cases from everyday clinical practice in order to build-up the overall knowledge and share experience which is complementary to available guidelines. Individual reports of difficult to treat cases, especially when additional diagnoses are involved, can be helpful for physicians treating patients with common rheumatological diseases such as juvenile idiopathic arthritis.

Recommendations for the management of childhood juvenile idiopathic arthritis-type chronic anterior uveitis.

Australian- and New Zealand-based, uveitis-specialized ophthalmologists have produced recommendations for the management of juvenile idiopathic arthritis (JIA)-type chronic anterior uveitis. Historically, the visual prognosis of JIA-type chronic anterior uveitis has been poor. New medical advances are likely to improve outcomes, but recently published guidelines are tailored for ophthalmic care in Europe and the United States. This work involved a consensus survey and a panel meeting. The Australian and New Zealand JIA-Uveitis Working Group (29 ophthalmologists) participated in the work. The Delphi technique was used to achieve consensus. This work yielded consensus statements. The Working Group achieved consensus around 18 statements related to clinical evaluation, use of topical and regional corticosteroids, use of systemic corticosteroid and non-corticosteroid immunomodulatory drugs, and management of secondary cataract and glaucoma in childhood JIA-type uveitis. Recommendations of the Australian and New Zealand JIA-Uveitis Working Group provide current and regionally applicable advice for managing chronic anterior uveitis in children with JIA.

Current status of MR imaging of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic arthropathy in the pediatric population. Although the diagnosis is essentially clinical for many affected joints, MR imaging has become an important tool for the assessment of joints that are difficult to evaluate clinically, such as temporomandibular and sacroiliac joints, and for screening of inflammatory changes in the entire body by whole body MRI (WBMRI) assessment. The utilization of MR imaging is challenging in the pediatric population given the need for discrimination between pathological and physiological changes in the growing skeleton. Several multicentric multidisciplinary organizations have made major efforts over the past decades to standardize, quantify, and validate scoring systems to measure joint changes both cross-sectionally and longitudinally according to rigorous methodological standards. In this paper, we (1) discuss current trends for the diagnosis and management of JIA, (2) review challenges for detecting real pathological changes in growing joints, (3) summarize the current status of standardization of MRI protocols for data acquisition and the quantification of joint pathology in JIA by means of scoring systems, and (4) outline novel MR imaging techniques for the evaluation of anatomy and function of joints in JIA. Optimizing the role of MRI as a robust biomarker and outcome measure remains a priority of future research in this field.

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.

Shoulder and Elbow Surgery in Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory arthropathy that manifests itself prior to the age of sixteen years with symptoms lasting six weeks or longer. As JIA frequently effects the upper extremities, activities of daily living become compromised during the stages of development when young adults are striving for independence. Symptomatology includes ankylosing, pain and early growth plate closure. Patients with joint involvement prior to growth plate closure have the most destruction in terms of joint abnormality and surgical complexity.Medical management of JIA has allowed for better non-surgical management, yet, there is a continued need to understand the appropriate surgical intervention and order for the greatest functional gains. Comparative studies have shown that varied results as to whether the shoulder replacement should supersede the elbow replacement or should that be reversed or both joint replacements done simultaneously. Our experience found a more significant functional improvement after total elbow replacement due to the unpredictable nature from the shoulder replacement outcomes and an inability for patients to do simple tasks such as bringing a cup to their mouths or handling a toothbrush. The exception to this occurs if the ipsilateral shoulder joint is severely limited to the point that the stressors placed on the elbow due to compensation will lead to early loosening or failure of the elbow joint replacement.Various methods for performing joint replacement of the shoulder and elbow in the JIA population will be discussed. Soft tissue integrity including the functional status of the rotator cuff will be a consideration for which surgical procedure should be considered. Surgical approaches for the elbow present fewer options for improving pain and function in this patient population. Pre, peri and postoperative management is reviewed as careful attention to irregular bony dimensions and dysmorphic anatomy precludes the use of standard implants.Total shoulder and total elbow arthroplasty should be considered in the JIA population where pain and significant functional compromise are present. The order of procedures is dependent on multiple factors and expected outcomes. Educating patients on postoperative expectations over the lifespan is an important part of surgical management for patients with JIA.

50 Years Ago in The Journal of Pediatrics: Revolutionary Changes in the Management of Juvenile Idiopathic Arthritis

50 Years Ago in The Journal of Pediatrics: Revolutionary Changes in the Management of Juvenile Idiopathic Arthritis

SAT0495 LONG TERM OUTCOME OF JUVENILE IDIOPATHIC ARTHRITIS IN ADULTHOOD; THE MONOCENTRIC EXPERIENCE OF 520 PATIENTS FOLLOWED FOR 20 YEARS IN A TRANSITION TERTIARY CLINIC OF PEDIATRIC RHEUMATOLOGY.

Background:Juvenile Idiopathic Arthritis (JIA) is a chronic pediatric inflammatory disease that shows many differences compared to adult-onset arthritis. The different clinical manifestations, the assessment and the management of JIA is the reason that the transition from childhood to adulthood is an important multidimensional process that emphasizes a lot of aspects.Objectives:To describe the long-term outcome of JIA.Methods:Five-hundred and twenty patients affected by JIA and referred to a transition care rheumatology tertiary centre were considered between 1999 and 2019. The outcome assessment included remission, disease duration, medications, number of prosthesis implantation, pregnancies, mortality and social integration (employment status and educational level).Results:A hundred and thirty-eight (26%) males and 382 (73%) females were included; 157 (30%) patients were lost to follow up. The mean age of the patients was 27 (18-57) years, with a mean age at onset of 8 years and an average disease duration of 19 years. Subtypes of JIA at disease onset included 252 (48%) oligoarthritis, 134 (26%) polyarthritis, 64 (12%) systemic arthritis, 22 (4%) psoriatic arthritis, 43 (8%) enthesitis related arthritis and 1 (0.1%) undifferentiated arthritis. Ninty-three (18%) patients suffered of uveitis. Ninty-five implant prosthesis and 16 arthrodesis were recorded. At follow up 198 (38%) patients were on remission of which 107 (20%) off medication. Among the 322 patients still on medication, 84 (16%) were under treatment with oral steroids, 226 (43%) with sDMARDs and 249 (40%) with bDMARDs. Five deaths (1%) occurred in this cohort. Two hundred and thirty-five subjects had a higher educational level, 327 had an employment. We have data of twenty-nine pregnancies. The transition age was considered after the age of 16 years old. The key word for the management of this cohort was the multidisciplinary approach towards each patient, with the collaboration of other specialists (ophthalmologist, orthopedic, dermatologist, gastroenterologist, obstetric and psychologist).Conclusion:In the era of biologic therapy the long-term outcome of JIA underwent an outstanding improvement regarding a lot of variables. Two hundred and thirty-two patients were still followed, not only because of the continuation of the biological therapy, but also for a multidisciplinary care even during remission. JIA often persists over the adulthood, therefore the long term follow-up and care of these patients needs to be conducted by a rheumatologist expertized in JIA in collaboration with other specialists.Disclosure of Interests:None declared

Assessing the reporting quality of physical activity programs in randomized controlled trials for the management of juvenile idiopathic arthritis using three standardized assessment tools

BackgroundThe reporting quality of physical activity (PA) programs in randomized controlled trials (RCTs) for the management of juvenile idiopathic arthritis (JIA) remains unknown. This study aimed to assess and compare the reporting quality of PA programs in RCTs for the management of JIA using three difference standardized assessment tools, and to describe the elements that were similar and different between these tools.MethodsA systematic search was conducted for moderate-to high-quality RCTs of PA programs in JIA, published up until January 2019. Two reviewers independently included 10 RCTs and scored the reporting quality of PA programs using the following tools: Consensus on Exercise Reporting Template (CERT) checklist, Consensus on Therapeutic Exercise Training (CONTENT) scale, and Template for Intervention Description and Replication (TIDieR) checklist.ResultsResults showed that reporting of PA programs in 10 moderate- to high-quality RCTs for JIA management remains incomplete. The average reporting quality (± standard deviation) for all RCTs combined was moderate for the three standardized assessment tools with 70.8 (±14.3)% for the TIDieR checklist, 53.2 (±20.2)% for the CERT checklist, and 70.0 (±18.9)% for the CONTENT scale. Despite some overlap, the three standardized assessment tools (TIDieR, CERT, CONTENT) included different elements resulting in different scores. All tools assess elements linked to PA programs (provider, location, timing, personalization and adherence), but the CERT checklist includes other essential elements (e.g., additional resources, motivational strategies, adverse events).ConclusionsThe lack of complete reporting of PA programs in RCTs for the management of JIA and the variation in scores and assessed elements among standardized assessment tools show the need to improve reporting. Using the most comprehensive standardized tool (i.e., the CERT) and providing accessible supplemental information on PA programs may improve the reporting quality of PA programs in RCTs and help reproduce PA programs in research and clinical practice.

PADI4 (rs2240340), PDCD1 (rs10204525), and CTLA4 (231775) gene polymorphisms and polyarticular juvenile idiopathic arthritis

ABSTRACT Background Certain single nucleotide polymorphisms (SNPs) in genes such as PADI4 (coding for peptidyl arginine deiminase 4), PDCD1 (coding for programmed cell death 1), and CTLA4 (coding for cytotoxic T-lymphocyte-associated protein 4) are linked to rheumatoid arthritis (RA). However, links between SNPs rs2240340, rs10204525 and rs231775 in PADI4, PDCD1 and CTLA4 respectively, and juvenile idiopathic arthritis (JIA), the commonest type of childhood arthritis, are unclear. We aimed to determine whether any of these SNPs are associated with JIA, and to clinical indices disease activity score (JADAS 71) and functional disability score (CHAQ). Methods We genotyped the three SNPs in 150 children with polyarticular JIA and 160 healthy children, recording standard health questionnaires, clinical features and laboratory markers. Results The TT genotype of PADI4 rs2240340 (aOR/95%CI 2.64: 1.31–5.30, P = 0.006) and CT genotype of PDCD1 rs10204525 (aOR/95%CI 4.99: 2.98–8.36, P < 0.0001) were associated with JIA. The AG+GG genotype of CTLA4 rs231175 was modestly linked to disease activity (aOR/95%CI 2.44 (1.19–5.04), p = 0.015). PADI4 rs2240340 was linked to CHAQ score (genotypes p = 0.013, alleles p = 0.006), whilst PDCD1 rs10204525 was linked to anti-CCP antibodies (genotypes p = 0.004), RF (genotypes p = 0.01), and the CHAQ score (genotypes p = 0.005, alleles p = 0.013). Conclusions There are various roles for these SNPs in PADI4, CTLA4 and PDCD1 in the diagnosis and, potentially, in the management of JIA.

Shoulder arthroplasty for juvenile idiopathic arthritis.

There is limited literature to guide shoulder surgeons in the management of juvenile idiopathic arthritis (JIA). We aim to help clinicians to formulate an approach to the surgical management of the condition through a review of the available literature on arthroplasty in JIA, general considerations when operating on patients with inflammatory arthropathy and recommendations based on the authors' experience. Four articles report formal data on arthroplasty in JIA with favourable improvements in post-operative pain and function scores after the long-term follow-up. Significant heterogeneity in treatment and a lack of standardisation in quantitative outcomes highlights the need for further larger scale and higher quality research. The aim of this study is to review the evidence and provide information on preoperative evaluation of surgical candidates, operative techniques, choice of implant design and to evaluate functional outcomes in patients who undergo shoulder arthroplasty.

Current management of juvenile idiopathic arthritis affecting the craniovertebral junction.

Craniovertebral instability is a rare and serious problem. While previously treated surgically, better understanding of disease processes has permitted the field to move towards conservative management. Juvenile idiopathic arthritis (JIA) is one cause of pediatric craniovertebral instability. Early recognition and institution of appropriate medical therapy and bracing in a multidisciplinary fashion is critical to avoid long-term instability, joint abnormalities, or morbid surgical procedures. We seek to highlight cases of this rare problem and provide a principled approach to management decisions. We review 6 cases that have presented over the last 6years and highlight 3 cases in particular regarding craniovertebral instability as a presentation of JIA. We reviewed the clinical records and radiographic features with particular emphasis of the stability of the craniovertebral junction. Age range of the subjects was from 5 to 12. All patients presented with neck pain and abnormal head rotation. Four of the patients responded to medical management and/or cervical bracing with no long-term sequelae or instability. Two patients had refractory rotary subluxation, one that responded to manual reduction under pharmacological paralysis and bracing; the other had an incompetent transverse ligament requiring surgical reduction and fixation. Neck pain and abnormal head rotation in an older child is rare finding but should prompt suspicion as a manifestation of JIA to the general pediatrician or initial provider. Appropriate serologic studies and MRI studies with contrast at the craniovertebral junction is necessary for evaluation. Early institution of medical management and cervical bracing under a multidisciplinary team of pediatric rheumatology and neurosurgery is key to avoiding surgical intervention and long-term abnormalities at the craniovertebral junction.

Treatment Withdrawal Following Remission in Juvenile Idiopathic Arthritis: A Systematic Review of the Literature.

Early diagnosis and treatment of juvenile idiopathic arthritis (JIA) with conventional and biologic disease-modifying anti-rheumatic drugs have vastly improved outcomes for children with these diseases. Currently, a large proportion of children with JIA are able to achieve clinical inactive disease and remission. With this success, important questions have arisen about when medications can be stopped and how to balance the risks and benefits of continuing medications versus the potential for flare after stopping. The aim was to conduct a systematic review of the available literature to summarize current evidence about medication withdrawal for JIA in remission. We conducted a systematic literature search in PubMed and Embase from 1990 to 2019. References were first screened by title and then independently screened by title and abstract by two authors. A total of 77 original papers were selected for full-text review. Data were extracted from 30 papers on JIA and JIA-associated uveitis, and the quality of the evidence was evaluated using National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) tools. Studies on biochemical and radiologic biomarkers were also reviewed and summarized. Most studies investigating treatment withdrawal in JIA have been observational and of poor or fair quality; interpretations of these studies have been limited by differences in study populations, disease and remission durations, the medications withdrawn, approaches to withdrawal, and definitions of disease outcomes. Overall the data suggest that flares are common after stopping JIA medications, particularly biologic medications. Clinical characteristics associated with increased risks of flare have not been consistently identified. Biochemical biomarkers and ultrasound findings have been shown to predict outcomes after stopping medications, but to date, no such predictor has been consistently validated across JIA populations. Studies have also not identified optimal strategies for withdrawing medication for well-controlled JIA. Promising withdrawal strategies include discontinuing methotrexate before biologic medications in children receiving combination therapy, dose reduction for children on biologics, and treat-to-target approaches to withdrawal. These and other strategies require further investigation in larger, high-quality studies. The published literature on treatment withdrawal in JIA has varied in design and quality, yielding little conclusive evidence thus far on the management of JIA in remission. Given the importance of this question, international collaborative efforts are underway to study clinical and biologic predictors of successful medication withdrawal in JIA. These efforts may ultimately support the development of personalized approaches to withdrawing medication in children with JIA in remission.

P38 Never say never: new onset uveitis in adolescence

Abstract Background To highlight the importance of considering new onset uveitis in adolescent patients with longstanding juvenile idiopathic arthritis (JIA). Methods We performed a retrospective review of electronic medical records. Results A 16 year-old girl was diagnosed in 2004, aged 15 months with extended oligoarticular JIA (ANA positive, &gt;1/640 homogeneous). Her initial treatment included intra-articular steroid injections and approximately eighteen months later methotrexate, which she remained on for four years. During this time she received occasional intra-articular steroid injections. Etanercept was added in 2009 due to persistent active disease and she continued on this treatment regime for the next five years. Methotrexate was discontinued in 2013 due to intolerance. Etanercept was discontinued in 2014 due to disease remission but was restarted after three months when her arthritis flared. In 2018 biologic treatment was changed due to poor disease control. Etanercept was switched to adalimumab, initially alternate weeks but increasing to weekly together with multiple joint injections. Six months later, her disease control remained poor and drug levels and antibodies were measured. She had a strongly positive anti-drug antibody level&gt;200 AU/ml and her adalimumab level was &lt;0.4mgs/L (normal range 5-10). At this time our patient now aged 16 presented with a four-week history of intermittent reduced vision in her right eye. Ophthalmology review found bilateral anterior uveitis. This patient had regular eye screening from her JIA diagnosis until her 11th birthday, showing no previous evidence of uveitis. Following diagnosis of uveitis she was commenced on steroid eye drops and IV methylprednisolone to treat both her uveitis and arthritis. Infliximab, (6mg/kg) was commenced then increased (10mg/kg) for ongoing uveitis and methotrexate was restarted. Despite this treatment she has persistent low grade right uveitis. Her left eye has settled and she has no lens opacities or raised intraocular pressures. She continues with joint discomfort secondary to her hypermobility but her arthritis is currently quiescent. Conclusion Type of arthritis and age at onset historically dictated the risk of developing uveitis. However uveitis can present in any age group and in patients with any type of JIA. In our case uveitis developed for the first time almost 15years after diagnosis. With disease modifying treatments now widely used early in the management of JIA, uveitis may be masked and therefore present late or atypically. It is rare for uveitis to present so long after diagnosis, however this case highlights that rheumatology teams should be aware that it can still develop. Therefore we should never say never! Conflicts of Interest The authors declare no conflicts of interest.

Treatment of juvenile idiopathic arthritis: what's new?

The present review highlights the advances in disease outcome achieved with currently available biologic medications and future perspectives for JIA management. In the last two decades, the management of juvenile idiopathic arthritis (JIA) has been revolutionized by appropriate legislative initiatives, the existence of very large collaborative networks and the increased availability of the novel biologic medications. A more rational approach to the management of JIA is being fostered by the recent publication of therapeutic recommendations, consensus treatment plans and for a treat-to-target strategy.

Validity and feasibility of the self-report EQ-5D-Y as a generic Health-Related Quality of Life outcome measure in children and adolescents with Juvenile Idiopathic Arthritis in Western Cape, South Africa.

BackgroundHealth-Related Quality of Life (HRQoL) data together with clinical findings allow for monitoring of intervention efficacy and the effect on HRQoL. Children with Juvenile Idiopathic Arthritis (JIA) experience symptoms often persisting into adulthood, emphasising the need to track HRQoL.ObjectivesThe aim of this study was to investigate psychometric properties of the EuroQol five-dimensional youth questionnaire (EQ-5D-Y) in children with JIA.MethodsA cross-sectional, analytical study design was used. Children 8 to 15 years were recruited, completing the self-report EQ-5D-Y and two other HRQoL questionnaires. Known group validity was established by comparing the effect size between children with different disease severities. Concurrent validity was tested using Kruskal–Wallis to compare the ranking of scores on different questionnaires. Feasibility was assessed by number of missing responses and time to complete each questionnaire.ResultsAll questionnaires were able to distinguish between children with different JIA severity. There was a significant difference in ranking of most Juvenile Arthritis Multidimensional Assessment Report dimension scores across EQ-5D-Y levels, (p < 0.05), indicating concurrent validity. There was poor concurrent validity with the PedsQL dimensions tested with EQ-5D-Y, except for ‘pain’ (p = 0.001). The EQ-5D-Y was the quickest to complete with no missing values.ConclusionThis study showed that the EQ-5D-Y is valid and feasible in measuring HRQoL in JIA children and adequately responsive to detect change over time.Clinical implicationsIt is quick and easy to use in a busy clinical setting, allowing for effective JIA management monitoring.

Biologics for the Treatment of Juvenile Idiopathic Arthritis.

Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases in children. Recently, the management of JIA has substantially changed, thanks to the availability of new treatment options, represented by biological drugs or biologics. These drugs modulate the specific mechanisms of the immune systems, such as TNF-α, IL-1 and IL-6 signaling, or lymphocyte activation and/or functioning. In this review, we provide a comprehensive discussion on the current recommendations and clinical evidence regarding the use of the available biologics in the treatment of JIA; moreover, the main pharmacokinetic and pharmacodynamic aspects of any specific biologic drug have been summarized.

A 10-Year Saudi Experience of Using Adalimumab in Treating Juvenile Idiopathic Arthritis

Background: Traditionally, management of Juvenile Idiopathic Arthritis (JIA) involves use of non-steroidal anti-inflammatory drugs (NSAIDS) or disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) or sulfasalazine; or steroids. However, in several cases, a low therapeutic response or important side effects is encountered. This study reports our experience in using adalimumab in JIA patients by assessing the efficacy and safety of this treatment in this category of patients. Methods: A retrospective study was conducted among 38 patients with JIA at the Pediatric Department, King Abdulaziz Univesrity Hospital, Jeddah, Saudi Arabia, in the period January 2005-March 2016. Patients’ records were reviewed and relevant demographic and clinical data were collected. Data were analyzed using SPSS version 21 and represented using tables. Results: The 38 patients were distributed as 11 (28.9%) males and 27 (71.1%) females; mean ± SD age was 11.91 ± 4.54 (range = 3 - 19) years. Mean ± SD (range) disease duration was 3.26 ± 2.52 (0 - 12) years and most frequent diagnoses included polyarticular rheumatoid factor (RF) negative form 12 (31.6%), followed by systemic and oligoarticular JIA with 9 (23.7%) cases each. Before adalimumab, fever was present in 13 (34.2%) cases, followed by rash in 8 (21.0%) cases; while 21 (55.3%) were asymptomatic. Thirty-one (81.6%) were in failure of MTX, 19 (50%) of steroids, 7 (18.4%) of NSAIDS and 3 (7.9%) had had intraarticular injections. Biologically, ANA, RF and anti-CCP were positive in 22 (57.9%), 8 (21.1%) and 4 (10.5%) of the cases, respectively. Uveitis was present in 11 (28.9%) of the patients. Analysis of adalimumab efficacy showed 10 (52.6%) cases of complete remission, 9 (23.7%) of partial remission and 9 (23.7%) other where treatment was discontinued. Major adverse effects included local pain (4 [10.5%]), new onset uveitis (1 [2.6%]) and rash (1 [2.6%]), responsible of 1case of treatment discontinuation. Predictors for complete remission on adalimumab were oligoarticular form (β = 3.450, p = 0.009) and negative RF (β = 2.381, p = 0.036); while predictors for nonresponse, whether complete or partial, were polyarticular form (β = ?3.784, p = 0.005) and positive anti-CCP (β = ?3.178, p = 0.021). Conclusion: Adalimumab is an efficient and relatively safe alternative in the treatment of JIA with relatively high remission rates and lower rates of adverse effects. Further multicentre experiences are warranted to prove its efficacy and safety in the Saudi patients.

Commentary on "Effects of Structured Exercise Training in Individuals With Juvenile Idiopathic Arthritis".

“How can I apply this information?” This systematic review supports the potential benefits of various types of exercise training in children with juvenile idiopathic arthritis (JIA). The evidence suggests that individuals with JIA can safely participate in exercise testing and exercise training without fear of harm. Since expert supervision of exercise training positively influenced outcomes in the studies, the role of the physical therapist is important to the functional well-being of this population. Evidence consistently supports that, in spite of advances in medical treatment, children with JIA are less physically active than their peers. In addition to targeting functional deficits through specialized interventions, therapists should promote achievement of recommended levels of physical activity. Therefore, clinicians treating children with JIA can play a key role in educating individuals, families, teachers, and caregivers regarding the safety and benefit of targeted exercise training in this population. “What should I be mindful about when applying this information?” The evidence suggests that specific supervised exercise programs improve functional outcomes of individuals with JIA. It is important to consider the practical accessibility of some of the specific programs presented in this review. Physical therapists should advocate on behalf of this patient population and educate referral sources on the value of physical therapy in the long-term management of JIA, to maximize function and peer-equivalent physical activity levels. There is a need for the development of an effective and sensitive instrument for measuring function and perception of function within this population. Finally, there appears to be value in interactive, media-based programs, which encourage consistent and successful participation in home exercise programs. Future research is needed to strengthen the evidence regarding specific forms of exercise training that are readily available to individuals with JIA. Paula Melson, PT, DPT, MMS Shannon Darnell, PT, MPT Cincinnati Children's Hospital Medical Center Cincinnati, Ohio