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Objective.To develop definitions for the assessment of magnetic resonance imaging (MRI) pathologies of the sacroiliac joints (SIJ) in juvenile idiopathic arthritis.Methods.An Outcome Measures in Rheumatology (OMERACT) consensus-driven methodology consisting of iterative surveys and focus group meetings within an international group of rheumatologists and radiologists.Results.Two domains, inflammation and structural, were identified. Definitions for bone marrow edema, joint space inflammation, capsulitis, and enthesitis were derived for joint inflammation; sclerosis, erosion, fatty lesion, and ankylosis were defined for assessing structural joint changes.Conclusion.Preliminary consensus-driven definitions for inflammation and structural elements have been derived, underpinning the ongoing development of the OMERACT Juvenile Arthritis MRI SIJ scoring system (OMERACT JAMRIS-SIJ).

Background:Juvenile Idiopathic Arthritis (JIA) is the most common auto-immune disease in children and pain is a common symptom. Despite treatment advances in recent years, pain often persists when the disease is inactive. Treating JIA to target has been widely recommended1, but effectiveness in pain reduction has not been proven yet2.Objectives:To compare pain scores over two years in three treatment arms in JIA patients that were treated to target and to identify baseline characteristics predicting unfavorable pain outcomes.Methods:DMARD naïve children who participated in the BeSt for kids study3 with oligoarticular JIA, RF negative polyarticular JIA and juvenile psoriatic arthritis were included. Patient were treated to target aimed at inactive disease according to 1 of 3 different treatment groups; 1) initial sequential DMARD monotherapy 2) initial methotrexate (MTX) with prednisolone bridging or 3) initial MTX with etanercept. Pain intensity was measured using a 100 mm Visual Analogue Scale during 24 months of follow up with 3-monthly intervals. Potential differences in VAS pain scores over time between treatment arms were compared using linear mixed models with random intercept and random slope for visits clustered within patients. A similar multivariable mixed model was used to assess the ability of several baseline characteristics to predict the chance of high pain levels during follow-up.Results:92 patients were randomized into the three treatment groups. Overall, pain scores over time reduced from mean 55.3 (SD 21.7) at baseline to 19.5 (SD 25.3) after 24 months. When comparing pain over time per arm, pain scores decreased significantly over time β -1.37 (95% CI -1.726; -1.022). No significant difference was found in pain over time between treatment groups (interaction term treatment arm*time (months) β (95% CI) arm 1 0.13 (-0.36; 0.62) and arm 2 0.37 (-0.12; 0.86) compared to arm 3), Figure 1. Correction for sex and symptom duration as possible confounders yielded similar results. Multiple baseline characteristics demonstrated a significant predictive value for pain over time: VAS pain (scale 0-100) with β 0.44 (95% CI 0.25; 0.65), VAS physician (scale 0-100) with β -0.34 (-0.55; -0.06), number of active joints with β 0.77 (0.19; 1.34), Child Health Questionnaire Physical summary Score with β -0.42 (-0.72; -0.11) and Psychosocial summary Score β -0.42 (-0.77; -0.06). Symptom duration, VAS patient/parent and NSAID use were no significant predictors, Table 1.Conclusion:Treatment to target seems effective in pain reduction in non-systemic JIA patients irrespective of initial treatment strategy. Several baseline predictors for pain over time were identified, which could serve as an initial indication for non-systemic JIA-patients with a high risk of pain despite a strict treat-to-target strategy.References:[1]Ravelli A, Consolaro A, Horneff G, et al. Treating juvenile idiopathic arthritis to target: recommendations of an international task force. Ann Rheum Dis. 2018;77(6):819–828.[2]Schoemaker, C.G., Swart, J.F. & Wulffraat, N.M. Treating juvenile idiopathic arthritis to target: what is the optimal target definition to reach all goals?. Pediatr Rheumatol. 18, 34 (2020)[3]Hissink Muller P, Brinkman DMC, Schonenberg-Meinema D, et al. Treat to target (drug-free) inactive disease in DMARD-naive juvenile idiopathic arthritis: 24-month clinical outcomes of a three-armed randomised trial. Ann Rheum Dis. 2019 Jan;78(1):51-59.Table 1.Baseline Characteristicsβp-value95% Confidence IntervalVAS Pain0.450.0000.25 to 0.65VAS Physician-0.310.014-0.55 to -0.06VAS Patient/parent-0.020.873-0.21 to 0.18No. of active joints0.770.0090.19 to 1.34PhS*-0.420.008-0.72 to -0.11PsS**-0.420.022-0.77 to -0.06Symptom duration (mo.)8.090.118-2.08 to 18.26NSAID use-1.300.791-10.91 to 8.31VAS Pain, VAS physician and VAS patient/parent was measures on a 100mm scale.*PhS= Physical Summary Score of the Child Health Questionnaire Parent form 50 (scale 0-100).**PsS= Psychosocial Summary Score of the CHQ-PF50 (scale 0-100).Disclosure of Interests:None declared

Background:Preliminary definitions for SIJ lesions in the OMERACT Juvenile Idiopathic Arthritis Magnetic Resonance Imaging score has been reported1. Investigators identified the need to revise the JAMRIS-SIJ item definitions.Objectives:To update the JAMRIS-SIJ definitions and scoring method.Methods:The OMERACT JAMRI working group was convened to discuss the performance of the score in a reliability exercise using 30 patients. Twenty investigators (12 radiologists, 8 rheumatologists) decided which definitions and scoring methods to be revised, retained or added.Results:The revised JAMRI-SIJ is in the Table 1.Table 1.Revised OMERACT JAMRIS-SIJ.ComponentDefinitionSegmentation/sliceScore range/sliceBone Marrow Edema (BME)An ill-defined area of high bone marrow signal intensity within the subchondral bone in the ilium or sacrum on fluid sensitive images4 quadrants/SIJ0-8BME IntensityPresence of hyperintensity of the marrow on fluid sensitive images using the signal of the presacral veins or cerebrospinal fluid as reference1 score/SIJ0-2BME DepthContinuing increased signal on fluid sensitive images of depth ≥ 5mm/ ≥ 1cm from the articular surface using the signal of the presacral veins or cerebrospinal fluid as reference1 score/SIJ0-2OsteitisAn ill-defined area of high bone marrow signal intensity within the subchondral bone in the ilium or sacrum on contrast enhanced T1 weighted sequences4 quadrants/SIJ0-8CapsulitisIncreased signal on fluid sensitive or contrast enhanced T1 weighted sequences involving the superior portion of the SIJ capsulesuperior halves/SIJ0-2Joint space fluidHigh signal intensity equivalent to the CSF on fluid sensitive sequences within the joint space of the cartilaginous portion of the SIJhalves/SIJ0-4Joint space enhancementIncreased signal intensity on contrast enhanced T1 weighted sequences within the joint space of the cartilaginous portion of the SIJhalves/SIJ0-4Inflammation in erosion cavityIncreased signal intensity on fluid sensitive or contrast enhanced T1 weighted sequences in an erosion cavity of the cartilaginous portion of the SIJhalves/SIJ0-4EnthesitisIncreased signal intensity in bone marrow and/or adjacent soft tissue on fluid sensitive or contrast enhanced T1 weighted sequences at sites where ligaments and tendons attach to a bone excluding retroarticular enthesitisScore per case0-1Damage DomainSclerosisA substantially wider than normal area of very low bone marrow signal intensity within the subchondral bone in the ilium or sacrum on a non-fat suppressed sequence, preferably a non-fat suppressed T1 weighted sequence. This feature must also be present on all other sequences, as available4 quadrants/SIJ0-8ErosionA focal loss of the low signal of cortical bone at the osteochondral interface and adjacent marrow matrix on T1 weighted images4 quadrants/SIJ0-8Fat metaplasia lesionHomogeneous increased signal intensity within the subchondral bone marrow on T1weighted images4 quadrants/SIJ0-8BackfillA high signal on non-contrast enhanced T1 weighted sequences in a typical location for an erosion, with signal intensity greater than normal bone marrow, clearly demarcated from adjacent bone marrow by an irregular band of low signal reflecting sclerosis at the border of the original erosionhalves/SIJ0-4AnkylosisPresence of signal equivalent to regional bone marrow continuously bridging a portion of the joint space between the iliac and sacral boneshalves/SIJ0-4Statement of overarching consideration for all definitions: “[…] in comparison to physiological changes normally seen on MRI examinations of age- and sex-matched children, and visible in 2 planes wherever available.”Conclusion:Revised JAMRIS-SIJ has been developed. Validation steps are underway.References:[1]Otobo TM, et al. Preliminary Definitions for Sacroiliac Joint Pathologies in the OMERACT Juvenile Idiopathic Arthritis Magnetic Resonance Imaging Score (OMERACT JAMRIS-SIJ). The Journal of rheumatology. 2019;46(9):1192-7.Acknowledgements:The authors acknowledge The Hospital for SickKids Research Trainee Competition (RESTRACOMP) and Queen Elizabeth II/Edward Dunlop Foundation Scholarship In Science and Technology (QEII-GSST) at the University of Toronto for funding provided to Dr. Tarimobo M. Otobo. The authors also acknowledge Prof. Dr. Desiree van der Heijde for providing expert commentary.Disclosure of Interests:None declared

Background:Young children with JIA have to cope with pain and fatigue during schooldays, facing problems with writing, climbing stairs, physical education and playing outside.1They need to develop age-appropriate self management skills, encouraged by their parents and teachers in a therapeutic alliance with the health professional team.2For this purpose a shared management tool, called the “Back and Forth Schoolbooklet”(B&FS), is developed, containing 1) Educational pages about JIA, pain and fatigue management 2) Diary pages with a colour-in puppet for expressing location and amount of pain, spaces for writing alternatives for limited activities, feedback spaces for parents and teachers and a self-evaluation scale of general well-being for the child. Children, parents and teachers are instructed how to use the booklet by therapists during outpatient rehabilitation. Structured evaluation of the use of the instrument is necessary to improve its applicability and effectiveness.Objectives:To study the feasibility, defined as practical and experienced applicability and effectiveness, of the B&FS.Methods:Pilot feasibility study with a mixed-method design. Parents, teachers, therapists and children with JIA were invited to fill in questionnaires after using the booklets in school. Adults had to sign informed consent. Practical applicability was assessed by multiple choice questions on duration and frequency of use. Used diary items and pages were counted in returned booklets. Experienced applicability and effectiveness were assessed by open-ended questions and 5 points Likert scales. Topics were experienced barriers, facilitators and benefits using the mentioned items of the booklets. Practical applicability was analysed descriptively. Atlas-ti8 was used for analysing and coding the answers on the open-ended questions using a thematic approach.Results:Eight children(4-8 years) used the booklets. Six parents of six children, four therapists and four teachers signed informed consent and answered questionnaires. Six booklets were returned.Practical applicability: Five children used booklets for a period of 2 to > 12 week, almost every day. One child stopped in the first week. Counting diary pages confirmed every day or every second day appropriate use of the color-in puppet and spaces for parents and teachers.Experienced applicability: Identified themes were: child-friendly, easy and providing a clear guide for the daily school situation. Themes as: daily obligation, unwillingness of the child, lack of motivation or time of the parents or teachers and insufficient instruction illustrated experienced barriers for the use of the booklet.Effectiveness: Identified themes: 1) Children express themselves better about feelings of pain and fatigue, 2) Parents and teachers appreciate more insight into how the child feels and 3)Teachers feel provided with guidance in the interaction with the child 4) Children feel more secure to express itself at school and 4) Parents are more relaxed about the schoolsituation.Likertscales showed that more than 75% of the users would advise the B&FS to other parents, teachers and therapists.Conclusion:The Back & Forth School booklet is a feasible shared management instrument to support young children with JIA in the school situation. A less rigid daily routine and sufficient instruction can improve the experienced applicability.References:[1]Tong, A. Children’s experiences of living with juvenile idiopathic arthritis. Arthritis Care Res. 2012;64(9):1392-1404.[2]Kieckhefer, G Supporting development of children with chronic conditions: from compliance toward Shared management. Pediatr Nursing, 2000;26(4).Figure 1Educational page: Pain managementFigure 2Diary pageAcknowledgments:Children, parents, teachers and therapistsDisclosure of Interests:None declared

Background In rheumatoid arthritis treatment, targeted treatment has shown to improve disease outcomes including the option of drug tapering and discontinuation. In non-systemic juvenile idiopathic arthritis (nsJIA) this has not been tried in a trial. Objectives To investigate which of three treatment strategies, targeting at drug-free inactive disease, is most effective and safe in recent onset DMARD-naive nsJIA. Methods We conducted a randomised, multicenter, treatment strategy study with 24 months of follow up. Patients, 2–16 years old with symptom duration Results 94 children (67% girls) with a median (InterQuartile Range) age of 9.1 (4.6–12.9) years were enrolled: 32 in arms 1 and 2, 30 in arm 3. Eleven had oligo-articular JIA, n=73 polyarticular JIA and n=8 juvenile psoriatic arthritis, 37% were ANA positive. At baseline VAS physician was median (IQR) 50 39–58 mm, VAS patient 54 37–70 mm, ESR 6 (2–14) mm/hr, active joints 8, 5–12 limited joints 2.5 (1–5), and CHAQ score 0.9 (0.6–1.5). After 24 months 61% (arm 1), 63% (arm 2) and 61% (arm 3) of patients had inactive disease and 45% (arm 1) 31% (arm 2) and 38% (arm 3) had stopped all DMARD(s). Time to inactive disease (median 9.0 (6.0–12.0) months) was not significantly different between arms, nor was time to flare (18.0 (15.0–21.0) months). Adapted ACRpedi-scores were comparably high between arms. Functional ability improved and remained almost normal. Toxicity reports showed mild events in similar rates across all arms. Results after 24 months by GEE. Conclusions Treatment to target drug free inactive disease is feasible in recent onset non-systemic JIA, resulting, regardless of initial treatment, in over 60% of patients in inactive disease and 38% drug free. Disclosure of Interest None declared

Combination therapy with prednisone or etanercept may induce earlier and/or more improvement in disease activity in Disease Modifying Anti Rheumatic Drug (DMARD) naive non-systemic Juvenile Idiopathic Arthritis (JIA) patients. Here we present three months clinical outcome of initial treatments of the BeSt-for-Kids study. Included patients were randomized to either: 1. initial DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate (MTX)), 2. Initial MTX / prednisolone-bridging, 3. Initial combination MTX/etanercept. Percentage inactive disease, adjusted (a) ACR Pedi30, 50 and 70 and JADAS after 6 and 12 weeks of treatment (intention to treat analysis) and side effects are reported. 94 patients (67% girls, 32 (arm 1), 32 (arm 2) and 30 (arm 3) with median (InterQuartileRange) age of 9.1 (4.7-12.9) years were included. 38% were ANA positive, 10 had oligo-articular disease, 68 polyarticular JIA and 16 psoriatic arthritis. Baseline median (IQR) ACRpedi-scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6.5 (2-14.8)mm/hr, active joint count 8 (5-12), limited joint count 3 (1-5), CHAQ score 0.88 (0.63-1.5). In arm 1, 17 started with MTX, 15 with SSZ. After 3 months, aACR Pedi 50 was reached by 10/32 (31%), 12/32(38%) and 16/30 (53%) (p = 0.19) and aACR Pedi 70 was reached by 8/32 (25%), 6/32(19%) and 14/30(47%) in arms 1-3 (p = 0.04). Toxicity was similar. Few serious adverse events were reported. After 3 months of treatment in a randomized trial, patients with recent-onset JIA achieved significantly more clinical improvement (aACRPedi70) on initial combination therapy with MTX / etanercept than on initial MTX or SSZ monotherapy. NTR1574 . Registered 3 December 2008.

Objective Children with juvenile idiopathic arthritis (JIA) experience functional impairment due to joint manifestations of the disease. The aim of our present study was to assess health-related quality of life (HRQOL) and its predictors in a group of children and adolescents with JIA. Methods The study sample includes all JIA patients (ages 6–18 years) who consulted a pediatric rheumatologist in Amsterdam, The Netherlands, between February 2009 and March 2010. HRQOL was measured using the Paediatric Quality of Life Inventory 4.0 (ages 6–18 years). Functional ability was measured using the Childhood Health Assessment Questionnaire, and medical and sociodemographic parameters were assessed. The study sample was compared to a Dutch youth norm population including children with other chronic health conditions. The proportion of children with JIA with an impaired HRQOL (

Inleiding Kinderen met een chronische ziekte kunnen problemen ondervinden op het gebied van kwaliteit van leven (KvL). Deze problemen zijn niet altijd bekend bij de kinderarts en worden meestal niet systematisch besproken. Echter, voor kind en ouder is het van belang dat hier aandacht voor is. Dit is mogelijk door middel van patient-reported outcomes (PRO’s): antwoorden van de patienten op vragenlijsten worden weergegeven in een PROfiel. Het PROfiel wordt door de arts met de patient besproken. Dit is de eerste studie naar het gebruik van een online PROfiel in de kindergeneeskunde.

This study aimed to determine disease activity patterns in juvenile systemic lupus erythematosus (jSLE) and its relation to early treatment. All jSLE patients who visited the outpatient departments of three Dutch university hospitals for at least 6 months were included. Data were retrospectively collected from each patient visit and hospitalization. Patient characteristics, clinical and laboratory findings categorized in organ systems, flare rate, medication use and disease course were analysed. Included were 35 patients (female 77%; White 47%) with a total follow-up of 142 years. Median age at diagnosis was 12.8 years. Flare rate was 0.45/patient-year. An organ system not earlier involved was affected in 34% of flares. Identifiable disease activity patterns were: chronic active (49%), relapse remitting (14%) and long quiescence (37%), with no significant difference in organ involvement at diagnosis. Positive anti-Sm and non-White ethnicity were significantly associated with a chronic active pattern. In 14 patients with severe symptoms at diagnosis, treatment with intravenous cyclophosphamide and/or biologics and/or intravenous methylprednisone in the first 6 months resulted in a long quiescence pattern in seven patients. In conclusion, distinct disease activity patterns are identifiable in children. Suppression of disease with early aggressive treatment may decrease the rate of progression. Lupus (2010) 19, 1550-1556.

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.

Glottal stops are conveyed by an abrupt constriction at the level of the glottis. Tracheoesophageal (TE) speakers are known to have poor control over the new voice source (neoglottis), and this might influence the production of 'glottal' stops. This study investigated how TE speakers realized 'glottal' stops in abutting words that end and begin with the same vowel. Ten phoneticians rated seven TE speakers' attempts to convey 'glottal' stops less favourably than two laryngeal control speakers' 'glottal' stops. Acoustic analyses showed that TE speakers relied on more gradual changes, but in 25% of realizations, a constriction at the neoglottis, similar to the constriction found in normal speakers, was produced. It was concluded that control over the neoglottis might be greater than is generally assumed. It might be possible to improve TE speakers' awareness and control over the neoglottis through training, using such tools as digital high-speed imaging.

OBJECTIVES: Most clinical studies use paper case record forms (CRFs) to collect data. In the Dutch multi-centre observational study on biologicals we encountered several disadvantages of using the paper CRFs. These are delay in data collection, lack of overview in collected data and difficulties in obtaining up-to-date interim reports. Therefore, we wanted to create a more effective method of data collection compared with CRFs on paper in a multi-centre study.METHODS: We designed a web-based register with the intention to make it easy to use for participating physicians and at the same time accurate and up-to-date. Security demands were taken into account to secure the safety of the patient data.RESULTS: The web-based register was tested with data from 161 juvenile idiopathic arthritis patients from nine different centres. Internal validity was obtained and user-friendliness guaranteed. To secure the completeness of the data automatically generated e-mail alerts were implemented into the web-based register. More transparency of data was achieved by including the option to automatically generate interim reports of data in the web-based register. The safety was tested and approved.CONCLUSIONS: By digitalizing the CRF we achieved our aim to provide easy, rapid and safe access to the database and contributed to a new way of data collection. Although the web-based register was designed for the current multi-centre observational study, this type of instrument can also be applied to other types of studies. We expect that especially collaborative study groups will find it an efficient tool to collect data.

ObjectivesJuvenile 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.MethodsA 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.ResultsSNPs in or near PTPN22, VTCN1, the IL2-IL21 region, ANKRD55 and TNFA were confirmed to be associated with JIA (pCD226 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).ConclusionsThe 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.

Objective: To evaluate the safety and efficacy of autologous stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA). Design: Retrospective analysis of follow up data on 34 children with JIA who were treated with ASCT in nine different European transplant centres. Rheumatological evaluation employed a modified set of core criteria. Immunological reconstitution and infectious complications were monitored at three month intervals after transplantation. Results: Clinical follow up ranged from 12 to 60 months. Eighteen of the 34 patients (53%) with a follow up of 12 to 60 months achieved complete drug-free remission. Seven of these patients had previously failed treatment with anti-TNF. Six of the 34 patients (18%) showed a partial response (ranging from 30% to 70% improvement) and seven (21%) were resistant to ASCT. Infectious complications were common. There were three cases of transplant related mortality (9%) and two of disease related mortality (6%). Conclusions: ASCT in severely ill patients with JIA induces a drug-free remission of the disease and a profound increase in general wellbeing in a substantial proportion of patients, but the procedure carries a significant mortality risk. The following adjustments are proposed for future protocols: (1) elimination of total body irradiation from the conditioning regimen; (2) prophylactic administration of antiviral drugs and intravenous immunoglobulins until there is a normal CD4+ T cell count.

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. JIA 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 …

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 13 277 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.

Item does not contain fulltext 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 2 years. RESULTS: Univariate analysis revealed association of the course of disease with JIA subtype (p=5.7*10(-5)) and three SNPs; VTCN1 rs10 923 223 (p=4.4*10(-5)), VTCN1 rs12 046 117 (p=0.017) and CDK6 rs42 041 (p=0.038). In a subsequent multivariate ordinal logistic regression analysis, VTCN1 rs10 923 223 (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.

Adductor spasmodic dysphonia (AdSD) is a controversial and enigmatic voice disorder. It is generally accepted that it has a neurologic, although undetermined, cause, and it is accompanied by much psychological and physical distress. In this prospective study, standardized psychometric tests were used to assess the personality characteristics and psychological and somatic well-being of 46 patients with AdSD. Moreover, the effect of botulinum toxin (Botox) treatment on their well-being was evaluated. No significant differences could be detected between patients and a representative norm group concerning 7 personality characteristics. Nevertheless, before treatment, there were significantly more psychological and somatic complaints. After establishment of a normal to near-normal voice with Botox injections, these complaints were reduced to normal levels — a finding suggesting these phenomena to be secondary to the voice disorder. These findings, and the normal personality characteristics, do not support a psychogenic cause of AdSD.

Objective: Juvenile idiopathic arthritis (JIA) is a chronic disorder in which both genetic and environmental factors are involved. Recently, we identified the TRAF1/C5 region (located on chromosome 9q33–34) as a risk factor for rheumatoid arthritis (RA) (p combined = 1.4×10 −8 ). In the present study the association of the TRAF1/C5 region with the susceptibility to JIA was investigated. Methods: A case–control association study was performed in 338 Caucasian patients with JIA and 511 healthy individuals. We genotyped the single nucleotide polymorphism rs10818488 as a marker for the TRAF1/C5 region. Results: The A allele was associated with the susceptibility to rheumatoid factor-negative polyarthritis with an 11% increase in allele frequency (OR 1.54, 95% CI 1.09 to 2.18; p = 0.012). This association was stronger when combining subtypes with a polyarticular phenotype (OR 1.46, 95% CI 1.12 to 1.90; p = 0.004). In addition, we observed a trend towards an increase in A allele frequency in patients with extended oligoarthritis versus persistent oligoarthritis (49%, 38% respectively); p = 0.055. Conclusions: Apart from being a well replicated risk factor for RA, TRAF1/C5 also appears to be a risk factor for the rheumatoid factor-negative polyarthritis subtype of JIA and, more generally, seems to be associated with subtypes of JIA characterised by a polyarticular course.

Objective. To assess the efficacy, tolerability, and safety of sulfasalazine (SSZ) in the treatment of juvenile chronic arthritis (JCA). Methods. We conducted a 24-week randomized, placebo-controlled, double- blind, multicenter study of patients with active JCA of both oligoarticular and polyarticular onset. Patients were treated with a dosage of 50 mg/kg/day of SSZ (maximum 2,000 mg/day) or placebo. The efficacy variables were joint scores, physician's, parents', and patient's overall assessments, and laboratory parameters of inflammation. Results. Of the 69 patients enrolled, 52 (75%) completed the trial. Six patients (18%) withdrew from the placebo group, and 11 (31%) withdrew from the SSZ group (P = 0.18). In the intention- to-treat analysis of end point efficacy, between-group differences were significant for the overall articular severity score (P = 0.02), all global assessments (P = 0.01), and the laboratory parameters (P < 0.001). Adverse events occurred more frequently in the SSZ group and were the main reason for withdrawal (P < 0.001), but in all instances, these events were transient or reversible upon cessation of treatment. Conclusion. The results of this first placebo-controlled study show that SSZ is effective and safe in the treatment of children with oligoarticular- and polyarticular-onset JCA, although it was not well tolerated in one-third of the patients.

Treatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biologics in 1999. Because of more insight in the cytokines involved in JIA the number of available biologic agents increased. Together with the introduction of these new drugs, new insights in the optimal treatment of JIA indicate that earlier and more aggressive therapy is associated with better outcomes. Whether these developments with regard to biologic treatment have resulted in better patients' outcomes in daily practice is not yet reported.

Children with juvenile idiopathic arthritis (JIA) experience functional impairment due to joint manifestations of the disease. The aim of our present study was to assess health-related quality of life (HRQOL) and its predictors in a group of children and adolescents with JIA.The study sample includes all JIA patients (ages 6-18 years) who consulted a pediatric rheumatologist in Amsterdam, The Netherlands, between February 2009 and March 2010. HRQOL was measured using the Paediatric Quality of Life Inventory 4.0 (ages 6-18 years). Functional ability was measured using the Childhood Health Assessment Questionnaire, and medical and sociodemographic parameters were assessed. The study sample was compared to a Dutch youth norm population including children with other chronic health conditions. The proportion of children with JIA with an impaired HRQOL (1 SD) was evaluated and multivariate regression analyses were performed to predict HRQOL outcome.Of the eligible patients, 64.1% (n = 152) participated. Both children (ages 6-12 years) and adolescents (ages 13-18 years) with JIA reported a significantly lower HRQOL in almost all domains compared to either healthy controls or children with other chronic health conditions. Approximately half of the children with JIA showed an impaired HRQOL. The main predictors of HRQOL were functional ability, pain, subjective burden of medication use, and school absence.The HRQOL is severely affected in children and adolescents with JIA. These findings underline the necessity to systematically monitor HRQOL in daily clinical practice.

Objective. 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. Methods. Detailed clinical data on different parameters describing the disease activity in sequential time periods covering the first 2 years after diagnosis were retrieved from the charts of 311 patients with JIA and compared between subtypes. In a cohort of 146 patients, the relation of these different clinical variables to the course of disease in the following 3 years was evaluated. Results. The percentage of time with active disease in the first 2 years differed significantly between subtypes. In all subtypes, a broad spectrum of activity was observed. The time with active disease in the first 2 years was the most significant factor associated with the duration of active disease in the following years. Conclusion. Different percentages of time with active disease have been observed between JIA subtypes in the first 2 years. The cumulative duration of activity varied widely within each subtype. Regarding the prognosis of the individual patient, the clinical course in the first 2 years appears to be predictive of the clinical course in the following years. Patients that have less time with active disease in the first 2 years are not likely to develop an unremitting clinical course later on.

To assess possible relationships between disease activity, foot-related impairments, activity limitations and participation restrictions in children with juvenile idiopathic arthritis (JIA).Thirty-four children were studied. Disease activity was assessed with the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Foot-related impairments, activity limitations and participation restrictions were measured with the Juvenile Arthritis Foot Disability Index (JAFI), the Childhood Health Assessment Questionnaire (CHAQ), self-reported or parent-reported and doctor-reported VAS scales. Relationships were quantified with Spearman's correlation coefficient.The mean age was 12.4±3.7 years, the median disease duration 1.5 years (interquartile range (IQR) 1.0-4.0), 88% were girls, and 76% had polyarticular disease course. The median JADAS-71 score (range 0-101) was 6 (IQR 1-13). On the JAFI sub-scores (range 0-4) 88% of the children reported some foot-related impairments (median 1.1, IQR 0.4-2.0); 82% reported some foot-related activity limitations (median 0.9, IQR 0.3-2.0), and 65% reported some foot-related participation restrictions (median 0.6, IQR 0-2.1). The median CHAQ score was 0.9 (IQR 0.1-1.8). The JADAS-71 correlated with all impairment, activity limitation and participation restriction variables (r=0.48-0.81, p0.01). Most of the impairment variables correlated with activity limitation (r=0.39, p0.05 to r=0.92, p0.01) and participation restriction variables (r=0.44, p0.05 to r=0.81, p0.01). All activity limitation variables correlated with participation restriction variables (r=0.62-0.84, p0.01).We observed strong relationships between disease activity, foot-related impairments, activity limitations and participation restrictions in children with JIA, and therefore suggest that standard screening for foot problems should be included in follow-up care for JIA patients.

Forty-seven patients with advanced larynx/hypopharynx, nasopharynx or oropharynx/oral cavity cancer were recorded before, and 10 weeks after concomitant chemoradiotherapy (CCRT), to investigate the effect of the tumor versus the effects of treatment. To evaluate voice functioning before and after treatment, voice quality and glottal behavior of sustained /a/ vowels were analyzed acoustically and compared with patient-based data on cigarette and alcohol usage. Acoustic measures of effort, nasality and regularity, such as periodicity or harmonics-to-noise ratio, differed significantly and progressed differently in dependence of the 3 distinct cancer/radiation sites. Baseline measures of voice stability correlated significantly with alcohol/smoking behavior.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is characterized by chronic arthritis and an autoimmune etiology. In several autoimmune diseases, including rheumatoid arthritis (RA), an association with the 4q27 locus has been reported. We undertook this study to investigate the possible role of the 4q27 locus in JIA. METHODS: A case-control association study was conducted, with a total of 655 Caucasian JIA patients and 791 healthy controls divided into 2 independent sample sets. The rs6822844 marker in the 4q27 locus was genotyped. RESULTS: In the first and larger sample set, a 5% decrease in T allele frequency was observed in patients compared with controls (allelic odds ratio [OR] 0.72 [95% confidence interval 0.55-0.95], P = 0.019), and in the second set, a 3% decrease was observed (allelic OR 0.81 [95% confidence interval 0.61-1.09], P = 0.169). The combined data set generated an OR of 0.76 (95% confidence interval 0.62-0.93, P = 7.08 x 10(-3)). When the different JIA subtypes were analyzed individually, significant decreases were seen in the subtypes with a polyarticular course of disease (extended oligoarthritis [P = 0.019] and rheumatoid factor-negative polyarthritis [P = 0.038]). CONCLUSION: Our findings suggest that the 4q27 locus, previously reported to be associated with RA, type 1 diabetes mellitus, celiac disease, and psoriatic arthritis, is also associated with susceptibility to JIA.

Objective:We undertook an observational study to obtain a complete overview of the long-term effectiveness and safety of etanercept in patients with different juvenile idiopathic arthritis (JIA) subtypes.Methods:At baseline we collected patient and disease characteristics of all Dutch patients with JIA who started treatment with etanercept. Disease activity was evaluated (at start of the study, after 3 months and then yearly) according to the JIA core set of the American College of Rheumatology paediatric definition for 30, 50 and 70% improvement (ACR Pedi 30, 50 and 70). Use of etanercept and concomitant drugs was monitored. Adverse events were recorded.Results:We included 146 patients with JIA with a median follow-up of 2.5 years per patient (range 0.3–7.3). JIA subtypes represented: 27% systemic, 8% polyarticular rheumatoid factor positive, 38% polyarticular rheumatoid factor negative, 19% oligoarticular extended, 3% enthesitis-related and 5% psoriatica. Most patients (77%) met the criteria of the ACR Pedi 30 in the first 3 months of treatment. For the majority of patients this improvement was sustained; 53 (36%) of all patients met the remission criteria. No other second-line agents were needed in 43 patients. Although patients with systemic JIA responded initially less to etanercept therapy than patients from other subtypes, those who did respond showed equal effectiveness in the long term. Serious adverse events rate was low (0.029 per patient year).Conclusions:Etanercept is effective and safe in JIA, even for a large proportion of the patients with systemic JIA. The greatest improvement occurred in the first 3 months of treatment, and was sustained for a long time in most patients (up to 75 months).

Objective:To report the short- and long-term results of two techniques (mental imagery and manual shaking of the larynx) in patients with non-organic dysphonia or aphonia.Design:Retrospective review of patient records, plus follow-up survey (questionnaire).Setting:Academic teaching hospital.Patients:One hundred and sixteen patients with moderate to severe non-organic dysphonia or aphonia.Outcome:Cure (i.e. normal voice) and improved voice quality, judged by clinicians and patients.Results:One hundred (86 per cent) of the 116 patients were cured. Ninety-four (81 per cent) patients regained their normal voice within one therapy session. The follow-up survey revealed that 43 of the 87 (49 per cent) patients who responded had not had a relapse since therapy ended. Of those patients suffering relapse, 15 successfully applied mental imagery in order to retrieve their voice, compared with three patients who applied shaking of the larynx.Conclusion:Mental imagery, combined if necessary with manual therapy, is an effective therapeutic technique in patients with non-organic voice disorders.

Objective To assess the safety and efficacy of intensive immunosuppression followed by T cell–depleted autologous hematopoietic stem cell transplantation (ASCT) for induction of disease remission in children with refractory progressive juvenile idiopathic arthritis (JIA). Methods Twenty-two patients with progressive refractory JIA were followed up over a median period of 80 months after pretreatment with intensive immunosuppression followed by ASCT in a multicenter, prospective, phase II clinical trial. Hematopoietic stem cells were harvested from the patients' bone marrow, depleted of T cells, and kept frozen until used for ASCT. Pretreatment of patients consisted of a combination of antithymocyte globulin, cyclophosphamide, and low-dose total body irradiation. Patients were followed up for ASCT-related complications, recovery of hematologic and immune system parameters, and disease outcomes. Results Reconstitution of hematologic values to normal range was rapid. Recovery of immune system parameters, especially normalization of CD4+, CD45RA+ naive T cells, was delayed, occurring at ≥6 months after ASCT. The prolonged period of immune deficiency resulted in a large number of viral infections and may have contributed to the development of macrophage activation syndrome (MAS), leading to death, in 2 patients. After ASCT, 8 of the 20 evaluable patients reached complete clinical remission of their JIA, 7 were partial responders, and 5 experienced a relapse of their disease (occurring 7 years after ASCT in 1 patient). Later during followup, 2 of the patients whose disease relapsed died from infections that developed after restarting immunosuppressive medication. Conclusion Intensive immunosuppression followed by ASCT resulted in sustained complete remission or marked improvement in 15 of 22 patients with progressive refractory JIA. The procedure, however, is associated with significant morbidity and risk of mortality due to prolonged and severe depression of T cell immunity. After fatal complications due to MAS were observed in some patients, the protocol was amended in 1999, to ensure less profound depletion of T cells, better control of systemic disease before transplantation, antiviral prophylaxis after transplantation, and slow tapering of corticosteroids. Following these protocol modifications, no additional ASCT-related deaths were observed among the 11 patients who received the modified treatment.

Objectives To explore patients9 perspectives on the use of imaging to support development of points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice.[1] Methods A task force has recently produced points to consider (PTC) for the use of imaging in the diagnosis and management of JIA in clinical practice. Given the challenges of asking children or young adults to attend consensus meetings with the task force members, a separate Patient and Public Involvement (PPI) event was arranged following the second task force meeting where the process and results were presented and all comments were recorded. The PPI event was attended by one child and two young adults with a diagnosis of JIA, two parents of children with JIA, two consultant rheumatologists, one with a special interest in paediatric rheumatology, a paediatric rheumatology nurse specialist and a paediatric research senior nurse. During thorough round table discussion thoughts and ideas related to a child9s experience of imaging for JIA were generated. Results There were extensive discussions around differences in the experience of imaging for children with JIA. Although the patients involved were young adults they had personal experience of JIA and also of imaging from early childhood (4 years old in one case). One had experienced conventional X-ray radiology (CR) and the other two had experienced CR, ultrasound (US) and magnetic resonance imaging (MRI). The PPI representatives gave no specific comments on the PTC as they felt they were directed towards medical staff but “thought they all sounded reasonable” and had no objections. However, they did make a number of overarching observations related to imaging in general, and on the individual imaging modalities (table). Conclusions This process has provided invaluable insight into understanding the patient perspective on various aspects of imaging in JIA. It highlights the importance of involving patients as far as possible in the development of clinical recommendations. In particular, key concerns related to the environment in which the imaging takes place, the ease of positioning and time taken, the importance of understanding the technology and having rapid access to a result. References Colebatch-Bourn AN, et al. EULAR-PRES points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice. Unpublished data, 2015. Disclosure of Interest None declared

Background In the BeSt for Kids (a three-armed treatment strategy study in juvenile idiopathic arthritis (JIA)) time to inactive disease, time to flare after Disease Modifying Anti Rheumatic Drug (DMARD) discontinuation, ACRpedi scores, functional ability, safety, and radiological damage are compared. Follow up will be 2 years. Here we present the 3 months clinical outcomes of initial treatments. Methods Recent onset, DMARD naive JIA patients (Rheumatoid Factor-negative polyarticular, oligoarticular or with psoriasis (ILAR-criteria), 2 /week, based on physician9s preference), 2. combination therapy: MTX 10mg/m 2 /week and 4 weeks prednisolone-bridging 0.5mg/kg/day, in 2 weeks tapered to nil, and 3. combination therapy with MTX 10mg/m 2 /week and etanercept 0.8mg/kg/wk. NSAIDs and intra-articular steroids are permitted in all patients. MTX was combined with folic acid 5mg/week. Treatment adjustments were made every 3 months after assessment by a trained, blinded examiner. Target was ACRpedi50 after 3 months and inactive disease from 6 months and onwards. Results From October 2009 to April 2014, 95 children, of which 33% boys, were enrolled: 32 in arm 1, 32 in arm 2 and 31 in arm 3. Baseline median (IQR) age was 8,6 (4,5-12,9) years. 38% were ANA positive, 12 patients had oligoarticular disease, 68 patients oligoextended/polyarticular JIA and 15 patients had JIA with psoriasis. Baseline median (IQR) ACRpedi scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6,5 (2-14,8) mm/hr, number of active joints 8 (5-12), number of joints with limited range of motion 3 (1-5), CHAQ score 0,88 (0,63-1,5). In arm 1, 17/32 had started with MTX, the others with SSZ. One patient in arm 1 (lost to FU) and 1 in arm 3 (uveitis) dropped out before 3 months. By 3 months ACRpedi50 was reached by 10/32 (31%),12/32 (38%) and 16/30 (53%) (p=0,19) and ACRpedi70 was reached by 8/32 (25%), 6/32 (19%) and 14/30 (47%) in arms 1-3, respectively (p=0.04). Toxicity (mainly gastrointestinal complaints) was similar in the treatment arms. Three short hospital admissions (serious adverse events) were reported. In 2/32, 1/32 and 2/30 patients MTX dose was reduced or switched to subcutaneous and 3/15 patients stopped SSZ after 6 weeks because of nausea, malaise, headache. Conclusions After 3 months of initial treatment in a three-armed strategy trial, patients with recent onset JIA achieve more clinical improvement (significantly more ACRpedi70) on initial combination therapy with MTX and etanercept than on initial MTX or SSZ monotherapy. Numerically, response to initial treatment with MTX and prednisolone bridging seems more effective than monotherapy and less effective than combination with etanercept, but these differences were not statistically significant. Disclosure of Interest P. Hissink Muller Grant/research support from: Pfizer, D. Brinkman: None declared, D. Schonenberg: None declared, Y. Koopman-Keemink: None declared, J. van den Berg: None declared, P. Bekkering: None declared, M. van Rossum: None declared, L. van Suijlekom-Smit: None declared, C. Allaart: None declared, R. ten Cate: None declared

In 2002, all children in the Netherlands from four to 18 years of age, including the Juvenile Idiopathic Arthritis (JIA) population, were vaccinated with the group-C meningococci conjugate vaccine. The aim of this study is to determine whether the vaccine increases JIA disease activity by monitoring the core set criteria of JIA patients as well as investigates the efficacy of this vaccine in those receiving DMARDs. The core set criteria included Childhood Health Assessment Questionnaire (CHAQ) disability, CHAQ pain, CHAQ well being, number of inflamed joints, range of motion, ESR, CRP, and semi-quantitative physicians global assessment. These were monitored for six months prior to as well as after vaccination for any changes in 86 JIA patients. Blood samples were taken from patients to measure antibody production using ELISA as well as T cell proliferation through intracellular fluorescent dye CFSE. In summary, no significant differences (P>0.05) were found when comparing the core set criteria six months before as well as six months after vaccination. However, there were significant increases of CD4+ T cell proliferation both against the carrier protein of the vaccine (P=0.034) as well as the whole vaccine (P=0.035). Furthermore, anti-Men C IgG antibody production increased significantly (>18µg/ml) irrespective of DMARD therapy. In conclusion, our data suggests that the group-C meningococci conjugated vaccine does not increase JIA disease activity. Moreover, B as well as T lymphocyte activity against group-C meningococci are not significantly diminished in patients undergoing immune suppressive treatments.

Background Chronic inflammatory activity in juvenile idiopathic arthritis (JIA) affects the bone, possibly resulting in growth abnormalities and decreased bone mineral density (BMD). Monitoring the bone status of JIA patients is important for the prevention of fractures and osteoporosis at later age. Dual-energy X-ray absorptiometry (DXA) is most widely used to determine BMD. BoneXpert is a new, feasible and reproducible method for automatic determination of cortical BMD on hand radiographs. Moreover radiation exposure is low and in low-risk peripheral areas. Objectives The aim of this study was to compare BoneXpert and DXA in the assessment of BMD in JIA patients. Methods Thirty-five JIA patients with available DXA and hand radiograph within a five month time period were included from a tertiary hospital of the Dutch Arthritis and Biologicals in Children register. Outcome measures for BMD were Bone Health Index (BHI) from BoneXpert and BMD total body, BMD lumbar spine and Bone Mineral Apparent Density (BMAD) from DXA. For all outcome measures Z-scores, reflecting the standard deviations compared to a healthy population, were calculated. Correlations between BMD measurements by DXA and BoneXpert were assessed with Pearson correlation coefficients. Results The patients in this study had significantly lower mean BMD compared to the healthy population on all BMD measures (p Conclusions BHI measured by BoneXpert is correlated to measurements of BMD by DXA. The correlation of Z-scores of BMD measured by the two methods is weaker. Longitudinal studies and assessment of the association of the BMD measurements with outcome (for instance atraumatic fractures) are necessary to further determine the value of BoneXpert in clinical use. Acknowledgements The authors wish to acknowledge Hans Henrik Thodberg for his support with and the free use of BoneXpert. Disclosure of Interest C. Nusman: None declared, J. Anink Grant/research support: Travel grant Pfizer, M. van Rossum Grant/research support: Travel grant Pfizer, R. van Rijn: None declared, M. Maas: None declared, L. van Suijlekom-Smit Grant/research support: For the submitted work: Dutch Board of health insurances, Pfizer and Abbvie. DOI 10.1136/annrheumdis-2014-eular.2869

Background Chronic inflammation combined with glucocorticoid treatment and immobilization put juvenile idiopathic arthritis (JIA) patients at risk of impaired growth and reduced bone mineral density (BMD). Conventional methods for evaluating bone age and BMD (such as manual evaluation using the Greulich and Pyle atlas and Dual-energy X-ray densitometry (DXA)) are time consuming, or come with high costs and additional radiation exposure. Objectives To evaluate feasibility and reproducibility of an automated method for determination of bone age and (cortical) bone mineral density (cBMD) in severely affected juvenile idiopathic arthritis (JIA) patients. A secondary objective was to describe bone age and cBMD in this specific JIA population, eligible for biologic treatment. Methods Prospectively included patients from two centres participating in the Dutch Arthritis and Biologicals in Children (ABC) Register between 1999 en 2012 were eligible for this study. Sixty-nine patients with standard hand radiographs at start of etanercept and calendar age within the reliability ranges of the programme (2.5-17 years for boys and 2-15 years for girls) were included. Radiographs were analysed with the BoneXpert method, automatically determining bone age and cBMD expressed as bone health index (BHI).[1] Bone age and BHI were expressed as absolute values, compared with reference values from a healthy population and subsequently expressed as Z-scores. Agreement between two measurements (reproducibility) and between left and right hand was assessed with the intraclass correlation coefficient (ICC). Regression analysis was used to identify variables associated with Z-scores of BHI. Results BoneXpert reliably evaluated radiographs of 67 patients (radiographs of two patients were rejected due to poor image quality). Agreement between repeated measurements (ICC 0.999-1.000) and left-right hand radiographs (ICC 0.838-0.996) was good. Mean Z-scores of bone age (-0.36, p=0.051) and BHI (-0.85, p Conclusions BoneXpert is an easy to use and reproducible method for assessing bone age and cBMD in patients with JIA, provided that radiographs are of reasonable quality and patients9 bone age lies within the age ranges of the program. The population investigated had delayed bone maturation and lower cBMD compared with healthy children. References Thodberg HH, van Rijn RR, Tanaka T, Martin DD, Kreiborg S. A paediatric bone index derived by automated radiogrammetry. Osteoporos Int. 2010 Aug; 21(8):1391-1400. Acknowledgements The authors wish to acknowledge Hans Henrik Thodberg for his support with and the free use of BoneXpert. Disclosure of Interest J. Anink: None declared, C. Nusman: None declared, L. van Suijlekom-Smit Grant/research support: For the submitted work: Dutch Board of health insurances, Pfizer and Abbvie, R. van Rijn: None declared, M. Maas: None declared, M. van Rossum: None declared DOI 10.1136/annrheumdis-2014-eular.3129

Biological therapy has dramatically improved the treatment of patients with JIA. However, there is still a group of patients that shows a lack of clinical response to this treatment. The use of robust predictive markers of response to identify individuals who are likely to respond to etanercept may provide guidance in optimizing treatment strategies.

Background Currently, biological agents are not approved for the treatment of persistent oligoarticular juvenile idiopathic arthritis (oJIA). However, there are persistent oJIA patients unresponsive to the conventional treatment consisting of NSAIDs, intra-articular corticosteroids (IAS) and methotrexate (MTX), in whom biological treatment is considered. Objectives We aimed to evaluate the effectiveness and safety of TNF-blocking agents in all Dutch patients with persistent oJIA included in the Arthritis and Biologicals in Children (ABC) register until February 2011. An additional aim was to explore if persistent oJIA patients treated with TNF inhibitors resemble other non-systemic JIA patients (patients with all JIA categories except systemic JIA) included in the register. Methods The Dutch Arthritis and Biologicals in Children Register is an ongoing multicenter prospective study which, since 1999, has aimed to include Dutch children with JIA using biological agents. Response to biological treatment was evaluated using the JIA core-set disease-activity variables and the Wallace criteria for inactive disease. Results Until February 2011, sixteen persistent oJIA patients (68.8% female) had been included in the register. Median age at onset was 8.4 years (IQR 2.1-13.5), 18.8% had a history of uveitis, and 56.3% were ANA-positive. All had previously been treated with MTX, and 81.3% with IAS. Most patients started etanercept; adalimumab was started in two patients who had active arthritis and uveitis. Median follow-up after introduction of biological treatment was 13.7 months (IQR 8.3-16.7). Though patients with persistent oJIA had less affected joints, they had similarly high patient/parent assessments of pain and wellbeing as other non-systemic JIA patients treated with TNF-inhibitors. Additionally, their physician evaluated the disease activity as moderately high. After 3 months of treatment, disease activity had decreased and the disease was inactive in 63% of patients. Joint counts decreased from a median of two (IQR1-4) to no active joints (IQR 0-2); the physician global assessment of disease activity decreased from median 36 (IQR 4-65) to zero (IQR 0-30). After 15 months the disease was inactive in 90% of patients. TNF-alpha blockers were tolerated well. Conclusions TNF-blocking agents seem an effective and justifiable option in persistent oJIA when treatment with IAS and MTX has failed. On some measures of disease activity, the persistent oJIA patients currently treated with TNF-inhibitors resemble other non-systemic JIA patients from our register. Larger studies are needed to identify factors that characterize these more severely affected persistent oJIA patients, so treatment strategy for these patients can be adapted in an early stage of the disease. Disclosure of Interest J. Anink: None Declared, M. Otten: None Declared, F. Prince: None Declared, E. Hoppenreijs: None Declared, N. Wulffraat: None Declared, J. Swart: None Declared, R. ten Cate: None Declared, M. van Rossum: None Declared, J. van den Berg: None Declared, K. Dolman: None Declared, Y. Koopman-Keemink: None Declared, W. Armbrust: None Declared, S. Kamphuis: None Declared, P. van Pelt: None Declared, S. Gorter: None Declared, L. van Suijlekom-Smit Grant/Research support from: Dutch Board of Health Insurances, Pfizer International, Abbott, Consultant for: Pfizer International

Background Juvenile Idiopathic Arthritis (JIA) is the most frequent form of arthritis in children. There are 7 subtypes of JIA in all of which the hand and wrist can be affected (1,2). The consequences of inflammation in the hand and wrist can be far-reaching and may lead to serious impairments and deformities. General problems of hand and wrist are described in 80% of all children with JIA (2) without further specification of the impairments. These impairments need to be further investigated, in order to develop nonpharmacological preventive treatment. Objectives To investigate the prevalence of specific hand and wrist impairments in children with JIA Methods Cross-sectional design, in which all children and adolescents (0-21 years) were included, who were diagnosed between January 2003 and January 2008 for JIA at the Departments of Pediatric Rheumatology of the Jan van Breemen Institute and Emma Childrens’ Hospital AMC in Amsterdam, and who have been treated in these clinics since then. During control visits at the outpatient clinic, assessment of complaints such as pain and stiffness and the use of devices, was performed, together with a specialized standardized physical examination of the hand and wrist including scores for tenosynovitis, arthritis and joint deformities. Results Between October 2006 and March 2010, 169 children met the inclusion criteria, of which 122 (72% of the total cohort) were assessed according to the protocol: mean disease duration 2.4 year (range 0.3-4.5 years), 71% female, mean age 13.7 years (range 3-20 years) and JIA subtypes: Rf-polyarthritis (52%), oligoarthritis (29%), Rf+polyarthritis (7%), psoriatic arthritis (6%), enthesitis related arthritis (6%), systemic (0%) and undifferentiated JIA (0%). The prevalence of any hand and wrist complaint was 56% and 49%, respectively. In 54% the children experienced complaints at school, and in 17% during hobbies. In only 15% and 23% of the children there were signs of active arthritis in hand and wrist joints respectively, and in 3% stenosing tenosynovitis. The prevalence of any hand or wrist impairment was 34%. Most frequent impairments were: limited range of motion of wrist (22%), PIP (18%), and MCP joints (8%). Only 2 children showed Boutonniere deformities; there were no Swanneck deformities, no radiar or ulnar deviations of wrist and finger joints, and no tendon ruptures. Five children showed diminished grip force in both hands. In 18% and 9%, the children were using wrist braces and finger splints respectively, while 43% applied other devices like a laptop (20%) or an adapted pencil (26%) at school. Conclusions In 122 children with JIA (72% of the total cohort), there was a high prevalence of hand and wrist impairments, also without the presence of active clinical arthritis. References Cassidy JT, Petty RE. Chronic arthritis in childhood. In: Textbook of pediatric rheumatology, 2005; 106-260. Edited JT Cassidy and RE Petty; Philadelphia, Elsevier Saunders. Ravelli A, Martini A. Early predictors of outcome in JIA. Clin Exp Rheumatol 2003; S89-S93. Disclosure of Interest None Declared

Background Anti-citrullinated protein antibodies (ACPA) have a low prevalence in Juvenile Idiopathic Arthritis (JIA). Autoantibodies recognizing carbamylated protein (anti-CarP) are a promising new serological marker for ACPA negative Rheumatoid Arthritis and are associated with a more severe clinical course (Shi et al, 2011). Objectives To determine the presence of anti-CarP antibodies in sera of JIA patients and to investigate their prognostic value. Methods Samples of 249 patients with all subgroups of JIA, taken at different time points in their disease course and 107 healthy partially age matched controls were analyzed for the presence of anti-CarP antibodies as well as ACPA (commercial CCP2 ELISA). Cut-off for positivity was determined in the sera of the healthy controls as the mean plus two times standard deviation. Results The serum samples came from patients with all different subtypes of JIA (median age 12,1 years, IQR 8,1-15,7 median disease duration 2,2 years IQR 0,7-6,4) including 19 polyarticular rheumatoid factor positive patients. IgG antibodies recognizing carbamylated antigens were present in sera of 12,9% (32/249) of all JIA patients vs 2,8% (3/107) in the controls (p=0,002). Anti-CarP antibodies were detected in 58% (11/19) of the rheumatoid factor positive polyarticular JIA patients (p Conclusions Anti-CarP antibodies can be detected in sera of patients with JIA, mainly in the rheumatoid factor positive polyarticular subgroup, which is the JIA subtype that shows the most resemblance with RA in adults. Correlations between anti-CarP antibodies and disease characteristics are currently under investigation. References Shi J et al. Autoantibodies recognizing carbamylated protein are present in sera of patients with rheumatoid arthritis and predict joint damage. PNAS, October 2011;108(42):17372-7 Disclosure of Interest P. Hissink Muller Grant/Research support from: Pfizer and the Dutch League against Rheumatism, J. Anink: None Declared, J. Shi: None Declared, N. Levarht: None Declared, T. Reinards: None Declared, M. Otten: None Declared, M. van Tol: None Declared, C. Jol-van der Zijde: None Declared, C. Allaart: None Declared, E. Hoppenreijs: None Declared, Y. Koopman-Keemink: None Declared, K. Dolman: None Declared, J. van den Berg: None Declared, M. van Rossum: None Declared, L. van Suijlekom-Smit: None Declared, M. Schilham: None Declared, R. ten Cate: None Declared, R. Toes: None Declared, L. Trouw: None Declared

Currently, little is known about when or how to stop etanercept in patients with juvenile idiopathic arthritis (JIA) when a good clinical response is reached, and therefore no guidelines are available.1 We evaluated the disease course of patients with JIA who discontinued etanercept because of a sustained good clinical response. This study is embedded in the Arthritis and Biologicals in Children (ABC) project, a prospective ongoing multicentre, observational study that includes all Dutch patients with JIA who used etanercept since 1999.2 3 We selected all patients who discontinued etanercept because of sustained good clinical response determined by the treating doctor. The outcome measures to assess disease activity consisted of the JIA core set of …

Juvenile Idiopathic Arthritis (JIA) is accompanied by uveitis in approximately 20% of the cases. This is a serious complication with risk of impaired vision or even blindness. Both conditions are considered to be autoimmune diseases. Since uveitis is often asymptomatic, frequent ophthalmologic checks are needed to diagnose this complication at an early stage. Identification of risk factors for uveitis (besides presence of antinuclear antibodies (ANA)) could contribute to understanding of the pathogenesis of both diseases, and could be used as prognostic tool in an individual patient.