Characteristics of JIA-associated uveitis at the age of transition

BackgroundJuvenile idiopathic arthritis (JIA) is the most common rheumatic disease in pediatric population and is characterized by a heterogeneous group of diseases that include chronic arthritis of unknown origin, which...

BackgroundJuvenile idiopathic arthritis (JIA) is the most common systemic disease causing uveitis in childhood and adolescence. JIA-associated uveitis has an estimated prevalence ranging from 11% to 30%, being higher in...

New early low-invasive biomarkers are demanded for the management of Oligoarticular Juvenile Idiopathic Arthritis (OJIA), the most common chronic pediatric rheumatic disease in Western countries and a leading cause of disability. A deeper understanding of the molecular basis of OJIA pathophysiology is essential for identifying new biomarkers for earlier disease diagnosis and patient stratification and to guide targeted therapeutic intervention. Proteomic profiling of extracellular vesicles (EVs) released in biological fluids has recently emerged as a minimally invasive approach to elucidate adult arthritis pathogenic mechanisms and identify new biomarkers. However, EV-prot expression and potential as biomarkers in OJIA have not been explored. This study represents the first detailed longitudinal characterization of the EV-proteome in OJIA patients. Fourty-five OJIA patients were recruited at disease onset and followed up for 24 months, and protein expression profiling was carried out by liquid chromatography-tandem mass spectrometry in EVs isolated from plasma (PL) and synovial fluid (SF) samples. We first compared the EV-proteome of SF vs paired PL and identified a panel of EV-prots whose expression was significantly deregulated in SF. Interaction network and GO enrichment analyses performed on deregulated EV-prots through STRING database and ShinyGO webserver revealed enrichment in processes related to cartilage/bone metabolism and inflammation, suggesting their role in OJIA pathogenesis and potential value as early molecular indicators of OJIA development. Comparative analysis of the EV-proteome in PL and SF from OJIA patients vs PL from age/gender-matched control children was then carried out. We detected altered expression of a panel of EV-prots able to differentiate new-onset OJIA patients from control children, potentially representing a disease-associated signature measurable at both the systemic and local levels with diagnostic potential. Deregulated EV-prots were significantly associated with biological processes related to innate immunity, antigen processing and presentation, and cytoskeleton organization. Finally, we ran WGCNA on the SF- and PL-derived EV-prot datasets and identified a few EV-prot modules associated with different clinical parameters stratifying OJIA patients in distinct subgroups. These data provide novel mechanistic insights into OJIA pathophysiology and an important contribution in the search of new candidate molecular biomarkers for the disease.

AB1034 NO DIFFERENCES IN HEPATITIS B ANTIBODY POSITIVITY IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS ON BIOLOGICAL THERAPY

Juvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and a limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated. To assess the clinical effectiveness and cost-effectiveness of four biologic DMARDs [etanercept (Enbrel(®), Pfizer), abatacept (Orencia(®), Bristol-Myers Squibb), adalimumab (Humira(®), AbbVie) and tocilizumab (RoActemra(®), Roche) - with or without methotrexate where indicated] for the treatment of JIA (systemic or oligoarticular JIA are excluded). Electronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and the Database of Abstracts of Reviews of Effects were searched for published studies from inception to May 2015 for English-language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence. Systematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost-utility decision-analytic model was developed to compare the estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base-case time horizon was 30 years and the model took a NHS perspective, with costs and benefits discounted at 3.5%. Four placebo-controlled randomised controlled trials (RCTs) met the inclusion criteria for the clinical effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi)-30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar, with fewer disease flares and greater proportions of ACR Pedi-50 and -70 responses among participants randomised to continued biologic DMARDs. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that, generally, ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between the treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality-of-life studies were included, one of which informed the cost-utility model. The incremental cost-effectiveness ratios (ICERs) for adalimumab, etanercept and tocilizumab versus methotrexate were £38,127, £32,526 and £38,656 per quality-adjusted life year (QALY), respectively. The ICER for abatacept versus methotrexate as a second-line biologic was £39,536 per QALY. The model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs, and clinical evidence for specific JIA subtypes is limited. Biologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA who have had an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow-up are needed to establish comparative effectiveness. RCTs for JIA subtypes for which evidence is lacking are also required. This study is registered as PROSPERO CRD42015016459. The National Institute for Health Research Health Technology Assessment programme.

Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and is one of the major causes of morbidity and physical disability. Due to frequent absences, children with chronic health impairments are also often confronted with educational difficulties. The aims of this study were to assess the impact of JIA on children’s schooling and to determine the factors that influence their school level. Methods This is a cross-sectional study including patients with JIA (ILAR criteria). A detailed questionnaire was completed for each participant by interviewing them or their parents as well as by information obtained from their medical records. Collected data included age, sex, subtype of JIA, disease duration, level of disability according to the Childhood Heath Assessment Questionnaire (CHAQ), visual analogue scale for patient’s overall assessment of disease activity (VASOA), duration of morning stiffness, tender joint counts (TJCs), swollen joint counts (SJCs), erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP), Disease Activity Score (DAS28) for polyarticular and oligoarticular JIA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for Enthesitis-related arthritis. Medications used for JIA treatment were also documented. Data on the school performance of patients and their siblings were obtained using telephone interviews (educational level, absenteeism, school delay by repetition, drop-out). Results A total of 43 patients with JIA were included, 25 female and 18 male, with a mean age of 26 years [12–51] and a mean disease duration of 237 months (5–496). The average age of the onset of the disease was 7.4 years [1.5–16]. The most common subtype was rheumatoid factor-positive polyarthritis (n = 18) followed by systematic (n = 8), oligoarticular (n = 8), rheumatoid factor-negative polyarthritis (n = 5) and Enthesitis-related arthritis (n = 4). The mean DAS28 was 3.02 [0.76 – 5.55] and the median CHAQ was 0.66 [0–3]. Twenty-nine of the children were receiving corticosteroid. Disease-modifying anti-rheumatic drugs were used by 38 of the 43 patients: methotrexate (n = 27), sulfasalazine (n = 8), leflunomide (n = 7), biotherapies (n = 16). Twenty patients had complications: Hip arthritis (n = 18), growth stunting (n = 14), uveitis (n = 5). Joint replacement was required in 11 cases. Four patients were illiterate, 14 had dropped out of school, 24 reported repeated absences due to illness. A year of schooling was repeated by 50.85% of patients. Eleven out of 32 patients over the age of 20 had an university level. Almost 80% of patients were exempted of physical education. There were no significant associations between the school-related problems, the socio-demographic characteristics and the various parameters of clinical and biological activity studied. Conclusion Our study suggested that JIA negatively affects schooling of children. More studies, with a larger sample of children, are needed to identify the variables associated with school failure in order to ensure the proper management of these patients and to increase their academic performance.

Background Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in the pediatric population. Methotrexate (MTX) has been considered as the cornerstone of treatment of poly and oligoarticular subtypes of JIA. However, this treatment is supposed to be for long term, which may involve an obstacle for adherence. The aims of the study were to evaluate adherence of Tunisian JIA patients to MTX and to identify factors associated with high adherence to MTX. Methods A cross-sectional study including patients with confirmed JIA diagnosis, according to the International League of Associations for Rheumatology (ILAR) criteria, was performed. Demographic data as well as disease characteristics were obtained from medical records. Laboratory markers including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were collected. Adherence was measured, for patients under MTX for >3 months, using the 5-item Compliance Questionnaire Rheumatology (CQR5) (1). Patients were divided into two groups: group 1: High adherence (HA) for patients having a CQR5 ≥ 80% and group 2: low adherence (LA) for patients having CQR5 < 80%. A p inferior to 0.05 was considered statistically significant. Results The study included 29 patients (10 males and 19 females) with a mean age at disease onset of 9.1 ± 3.4 years. The mean disease duration was 61 ± 79 months [7–336]. JIA subtypes were in decreasing order of frequency as follows: enthesitis-related arthritis (n = 13), oligoarticular (n = 8), Polyarticular without rheumatoid factor (n = 4), Polyarticular with rheumatoid factor (n = 2), systemic (n = 1) and, psoriatic arthritis (n = 1). A biologic inflammatory syndrome was found in 48.3% (n = 14) of cases. The mean ESR and CRP were 20 mm/h ± 11.3 [3–98] and 5 ± 17.8 mg/l [0–56] respectively. Nineteen (65.5%) patients had coxitis. Overall, 55.17% of patients (n = 16) were treated with MTX with a mean weekly dose of 9.2 ± 3.2 mg [5–15]. MTX was orally administrated in all patients. NSAIDs and prednisone were prescribed in 51.7% (n = 15) and 17.2% (n = 5) of cases respectively. The MTX was associated with biological DMARDs in five patients (17.2%). It was about Etanercept in 4 patients and Tocilizumab in 1 patient. Mean CQR5 score was 70.8% ± 18 [25–100]. Only seven patients (43.8%) showed high adherence to MTX. The statistical study revealed no difference between HA and LA in term of gender (P = 0.84), age at disease onset (P = 0.39), disease duration (P = 0.9), prednisone use (P = 0.22), the occurrence of coxitis (P = 0.2), ESR (P = 0.83) and CRP (P = 0.033) rates. Conclusion In this study, less than one half of JIA patients were highly adherent to MTX according to CQR5. Low adherence should be considered before declaring MTX treatment failure.

TP2 INITIAL PRESCRIBING PATTERNS TRENDS IN NEWLY DIAGNOSED CHILDREN WITH NON-SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS IN US: ANALYSIS OF ELECTRONIC MEDICAL RECORDS FROM 2009 TO 2018

BackgroundJuvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Our group has recently demonstrated that extended oligoarticular and polyarticular JIA mostly evolve to a rheumatoid arthritis (RA)-like...

THU0534 Joint Hypermobility in Oligoarticular Juvenile Idiopathic Arthritis

BackgroundAuto-antibodies against carbamylated proteins (anti-CarP) are emerging biomarkers in rheumatoid arthritis with relevant prognostic value. Juvenile idiopathic arthritis (JIA) is characterized by high heterogeneity and risk-stratification could be improved.ObjectivesWe aim...

BackgroundJuvenile idiopathic arthritis-associated uveitis (JIA-U) can lead to poor visual outcomes and impact a child’s quality of life (QOL) and function. Our aim is to identify risk markers of JIA-U and examine differences in the QOL of children with JIA and JIA-U.MethodsRheumatology and ophthalmology record reviews and questionnaires were completed every 4–6 months on 287 children with JIA. We collected arthritis, uveitis, and QOL data. We examined data through last study visit.ResultsThere were 52/287 (18 %) children with JIA-U who were younger at arthritis diagnosis, had oligoarticular persistent JIA, and ANA positive. Confirmed uveitis predictors were age at JIA diagnosis (OR = 0.86) and oligoarticular subtype (OR = 5.92). They had worse vision specific QOL and function, but similar general QOL. Blindness occurred in 17.5 % of children but was more common in African American children compared to non-Hispanic Caucasian children ((5/7 (71 %) vs. 2/29 (7 %), p <0.001) despite a similar uveitis prevalence (22 % vs. 16 %). Both races had similar complications, although band keratopathy was more frequent in African Americans (75 % vs. 15.6 %, p = 0.003).ConclusionsWe confirm young age at JIA diagnosis and the oligoarticular JIA subtype as predictors of uveitis development. Although we were unable to identify predictors of ocular complications or blindness, AA children appeared to have a more severe disease course manifested by increased ocular complications, vision loss and blindness. Potential causes that warrant additional study include underlying disease severity, access to medical care and referral bias. Further investigation of the risk factors for vision-compromising uveitis and its’ long-term effects should be conducted in a large racially diverse population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12969-015-0018-8) contains supplementary material, which is available to authorized users.

JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs. • Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections. • Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies. • Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up. • The JADAS10 calculated at 3 and 6months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA.

Background:Juvenile arthritis is one of the most common rheumatic diseases in childhood. With all remission drugs, a high percentage of patients continue to have an active disease as young adults...

THU0171 Effect of Fast Escalation of The Dose of Subcutaneous Methotrexate on The Need for Biological Dmards in Patients with Very Early and Established Rheumatoid Arthritis