M.A. van Rossum

Major improvements in health-related quality of life during the use of etanercept in patients with previously refractory juvenile idiopathic arthritis

Objective: To evaluate changes in health-related quality of life (HRQoL) in patients with refractory juvenile idiopathic arthritis (JIA) who are being treated with etanercept. Methods: 53 patients with JIA from seven Dutch centres were included. HRQoL was measured by the Childhood Health Assessment Questionnaire (CHAQ), Child Health Questionnaire (CHQ) and Health Utilities Index mark 3 (HUI3) at the start and after 3, 15 and 27 months of treatment. At the same time points the following JIA disease activity variables were collected; physician’s global assessment through the visual analogue scale (VAS), number of active and limited joints and erythrocyte sedimentation rate. A statistical method linear mixed models was used to assess outcomes over time. Results: During etanercept treatment both disease-specific and generic HRQoL outcomes improved dramatically. Significant improvements were shown after 3 months and these improvements continued at least up to 27 months of treatment. The disease-specific CHAQ, including VAS pain and wellbeing, showed a significant improvement in all domains. The generic health-profile measure CHQ improved for all the health concepts except for “family cohesion”, which was normal. The generic preference-based HUI3 showed impairment and, subsequently, significant improvement in the more specific domains (“pain”, “ambulatory”, “dexterity”). In accordance disease activity variables also improved significantly over time. Conclusion: This study shows that the HRQoL of patients with refractory JIA can be substantially improved by the use of etanercept for all aspects impaired by JIA. Information on HRQoL is crucial to understand the complete impact of etanercept treatment on patients with JIA and their families.

EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice

To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13u2005277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion.

Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease involving chronic arthritis. The clinical course is characterized by a fluctuating pattern of active and inactive disease. We have described in detail the clinical course in different JIA subtypes during the first 2 years after diagnosis and studied its relationship to disease activity in the following years.

Anticarbamylated protein (anti-CarP) antibodies are present in sera of juvenile idiopathic arthritis (JIA) patients

In juvenile idiopathic arthritis (JIA) patients there is a lack of markers that predict severe disease. Although anticitrullinated protein antibodies (ACPA) have contributed substantially to the understanding of rheumatoid arthritis (RA),1 their detection in JIA has not been equally useful as incidence rates in JIA patients are low2 and merely confined to the polyarticular immunoglobulin (Ig)M-rheumatoid factor (RF)-positive category resembling RA. Recently, anticarbamylated protein (anti-CarP) antibodies were detected in 45% of RA patients and importantly also in 16%–20% ACPA-negative patients.3–5 Within the ACPA-negative patients, anti-CarP antibodies were associated with more severe radiographic progression.3 Since most JIA patients are ACPA-negative we investigated whether anti-CarP antibodies are present in the sera of JIA patients and how they are related to ACPA and IgM-RF.nnJIA patients from three Dutch sources were included: the BeSt for Kids trial (NTR 1574, a treatment strategy study) (n=33), a previously described cohort6 (n=48) and the Arthritis and Biologicals in Children (ABC) register7 (n=153). Healthy controls (n=107) (mean age/range 11/(2–20)) are stem-cell graft …

CD226 (DNAM-1) is associated with susceptibility to juvenile idiopathic arthritis

Objectives Juvenile idiopathic arthritis (JIA) is considered a complex genetic autoimmune disease. We investigated the association of genetic variants previously implicated in JIA, autoimmunity and/or immunoregulation, with susceptibility to JIA. Methods A genetic association study was performed in 639 JIA patients and 1613 healthy controls of northwest European descent. Ninety-three single nucleotide polymorphisms (SNP) were genotyped in a candidate gene approach. Results of the entire JIA patient group (all subtypes) were compared with results obtained, alternatively, with a clinically homogeneous patient group including only oligoarticular and rheumatoid factor (RF) negative polyarticular JIA patients (n=493). Meta-analyses were performed for all SNPs that have been typed in other Caucasian JIA cohorts before. Results SNPs in or near PTPN22, VTCN1, the IL2-IL21 region, ANKRD55 and TNFA were confirmed to be associated with JIA (p<0.05), strengthening the evidence for involvement of these genes in JIA. In the majority of these replicated SNPs, effect sizes were larger when analysing a homogeneous patient cohort than when analysing all subtypes. We identified two novel associations with oligoarticular and RF-negative polyarticular JIA: CD226 rs763361 (OR 1.30, 95% CI 1.12 to 1.51, p=0.0006) and CD28 rs1980422 (OR 1.29, 95% CI 1.07 to 1.55, p=0.008). Meta-analyses including reported studies confirmed the association of both SNPs with susceptibility to JIA (OR 1.16, p=0.001 and OR 1.18, p=0.001, for rs763361 and rs1980422, respectively). Conclusions The CD226 gene has been identified as novel association with JIA, and a SNP near CD28 as a suggestive association. Both genes are probable candidate risk factors, since they are involved in costimulation of T cells.

Genetic variation in VTCN1 (B7-H4) is associated with course of disease in juvenile idiopathic arthritis

Objective The course of disease in juvenile idiopathic arthritis (JIA) is unpredictable with episodes of activity and remission. In order to identify predictive factors, 93 SNPs, JIA subtype, age at onset and ANA status were studied in relation to disease course. Methods Genetic and clinical parameters were analysed in a cohort of 272 Caucasian patients with persistent oligoarthritis (n=129), extended oligoarthritis (n=57) and rheumatoid factor negative polyarthritis (n=86). Categories of disease course (remitting (n=65), intermediate (n=96) and unremitting (n=111)) were designed based on the cumulative time spent in active disease in the first 2u2005years. Results Univariate analysis revealed association of the course of disease with JIA subtype (p=5.7*10–5) and three SNPs; VTCN1 rs10u2005923u2005223 (p=4.4*10−5), VTCN1 rs12u2005046u2005117 (p=0.017) and CDK6 rs42u2005041 (p=0.038). In a subsequent multivariate ordinal logistic regression analysis, VTCN1 rs10u2005923u2005223 (OR 0.41, 95%-CI 0.26 to 0.63) and JIA subtype (OR 3.8, 95%-CI 2.0 to 7.2; OR 2.5, 95%-CI 1.4 to 4.2, for extended oligoarthritis and RF-negative polyarthritis vs persistent oligoarthritis, respectively) were the strongest independent factors for course of disease. Conclusions This study provides evidence that VTCN1, encoding B7-H4, is associated with course of disease in selected subtypes of JIA. VTCN1 might be useful in predicting the course of disease.

PReS-FINAL-2160: Intestinal microbiome in polyarticular juvenile idiopathic arthritis: a pilot study

The intestinal microbiome may play a role in the pathogenesis of Juvenile Idiopathic Arthritis (JIA). In IBD patients an overall decrease in microbial diversity of the intestinal microbiota has been observed. Studies comparing intestinal microbiome in children with JIA and healthy controls have not been conducted to date.

OP0297 Trends in Prescription of Biologics and Outcomes of Juvenile Idiopathic Arthritis; Results of the Dutch National Arthritis and Biologicals in Children Register

Background Treatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biologics in 1999. Because of more insight in the immunological and biological pathways involved in the development of JIA the number of available biologic agents increased. Together with the introduction of these new drugs, also new insights in the optimal treatment of JIA indicate that earlier and more aggressive therapy is associated with better outcomes. Whether these new insights with regard to biologic treatment have been adopted in daily practice and resulted in better patients’ outcomes is not yet reported. Objectives o evaluate trends in prescription of biologics and influence on outcomes of Dutch JIA patients that started their first biologic between 1999 and 2010. Methods The Arthritis and Biologicals in Children register (a multicenter prospective observational study) aims to include all JIA patients in the Netherlands who use or used biologic agents since 1999. Patients were divided in time periods according to the year of introduction of first biologic agent. Trends in characteristics of patients before introduction of first biologic and effectiveness of the first biologic were analyzed over a 12 year period. Results 343 non-systemic and 86 systemic JIA patients started at least 1 biologic agent between 1999 and 2010. Etanercept remained biologic of first choice for non-systemic JIA and anakinra has become first choice for systemic JIA. The use of systemic prednisone and synthetic disease-modifying anti-rheumatic drugs (besides methotrexate) prior to biologics decreased. During these 12 years of observation, biologics were prescribed after shorter disease durations; the proportion of patients with less than 1.5 years of disease duration before start of the first biologic agent increased from zero in the years 1999-2001 to 31% in 2008-2010. Disease activity and acquired sequelae at baseline decreased with regard to number of joints with arthritis (median of 18 active joints in 1999-2001 to 5 in 2008-2010), number of joints with limited motion (median of 12 limited joints in 1999-2001 decreased to 3 in 2008-2010) and functional disability scores (median CHAQ score of 1.8 in 1999-2001 decreased to 1.1 in 2008-2010). For systemic JIA, prescription patterns changed towards introduction in patients with higher ESR values. These changes for both systemic and non-systemic JIA resulted in more patients with inactive disease and less joints with limited motion after 3 and 15 months of treatment. Conclusions Biologics are prescribed increasingly, are introduced earlier during the disease course and in JIA patients with lower disease activity. These changes are subsequently accompanied by better short-term disease outcomes. Etanercept remains biologic of first choice for non-systemic JIA and anakinra has become first choice for systemic JIA. Disclosure of Interest M. Otten Grant/research support from: Abbott, Novartis, Roche, Pfizer, Consultant for: Roche, J. Anink: None Declared, F. Prince Grant/research support from: Abbott, Bristol-Myers Squibb, Novartis, Tevapharma, and Pfizer, Consultant for: Roche, M. Twilt: None Declared, S. Vastert: None Declared, R. ten Cate Grant/research support from: Pfizer, Consultant for: Pfizer, E. Hoppenreijs: None Declared, W. Armbrust: None Declared, S. Gorter: None Declared, P. van Pelt: None Declared, S. Kamphuis Grant/research support from: Pfizer, K. Dolman: None Declared, J. Swart: None Declared, J. van den Berg: None Declared, Y. Koopman-Keemink: None Declared, M. van Rossum: None Declared, N. Wulffraat Grant/research support from: Pfizer, Novartis and Roche, L. van Suijlekom-Smit Grant/research support from: Dutch Board of Health Insurances, Dutch Arthritis Association, Pfizer, Abbott, Consultant for: Roche, Novartis

SAT0452 Distribution Pattern of MRI Abnormalities Within the Knee and Wrist of Juvenile Idiopathic Arthritis Patients; MRI made Easy

Background MRI plays an increasingly important role in the assessment and monitoring of disease activity in juvenile idiopathic arthritis (JIA). Awareness of the incidence and distribution pattern of MRI abnormalities in JIA is a valuable tool in the daily practice of the reading radiologist and the treating clinician. Preferred locations for pathology within target joints are facilitated by knowledge on common distribution patterns of MRI abnormalities, enabling rapid differentiation between JIA abnormalities and normal variants. Objectives To determine (1) incidence and (2) distribution pattern of soft-tissue- and osseous abnormalities upon MRI of the two of the most affected joints in JIA (i.e. the knee and wrist) Methods MRI datasets of 166 active JIA patients (123 with knee and 43 with wrist involvement) were analyzed. Two readers evaluated presence of 4 literature-based items per joint. Common items included synovial hypertrophy (SH), bone marrow changes (BMC), and bone erosions (BE). Joint-specific features were additionally evaluated: cartilage lesions (CL) for the knee and tenosynovits (TS) for the wrist. Scoring locations in these two joints were also literature-based. Incidence of each scored item was defined separately. Involvement per location, analyzed as percentage of the total amount of affected locations, was determined. Results SH showed the highest incidence in both the knee and wrist (56.9-65.1% of the patients). Besides BMC (34.1%), the incidence of osteochondral features was low in the knee (CL 6.5%; BE 4.9%). In contrast, the incidence of these features in the wrist were relatively high (BMC 37.2% and BE 30.2%) and TS was present in 46.5% of the patients with wrist involvement. In order to make MRI easy, ‘top-3-location’ per feature was constituted. Below, the ‘number 1’ or most frequently affected location per feature is mentioned. In the knee these locations consisted of cruciate ligaments (25.1% in SH), medial patella (28.1% in BMC, 33.3% in CL) and lateral femur trochlea (50% in BE). In the wrist, the radiocarpal joint (32.8% in SH), extensor-tendon-group (83.3% in TS), lunate (15.2% in BMC) and capitate/triquetrum (21.4% in BE) were mostly affected. Being the most important feature in JIA, SH in the knee showed preferred presence in the central locations, which accounted for >85% of the total affected locations. Less obvious demarcation for SH was found in the wrist. Both in the knee and wrist the three least affected locations of SH were never found to be involved without the presence of at least one of the three other most frequently affected locations. Conclusions This study provides an overview of incidence and distribution of a well-defined spectrum of MRI abnormalities within the knee or wrist of clinically active JIA patients. SH has highest incidence in both joints. In daily practice, a top-3-location per feature suggestive for pathology is helpful in navigation through the MRI of the knee or wrist in JIA patients. Disclosure of Interest None Declared