Persistent Oligoarticular Juvenile Idiopathic Arthritis Research Articles

When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?

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.

Adalimumab Effectively Decreases Inflammation Downstream of TNFα Signaling in Synoviocytes from Extended Oligoarticular Juvenile Idiopathic Arthritis.

Fibroblast-like synoviocytes (FLS) play a critical role in inflammation that contributes to disease progression in juvenile idiopathic arthritis (JIA). In rheumatoid arthritis (RA), FLS express tumor necrosis factor alpha (TNFα). TNFα signaling has been shown to be upstream of transforming growth factor beta (TGFβ) signaling. Overexpression of TNFα and TGFβ, as well as related proteins, can cause increased inflammation in RA. In this study, we examine the effects of inhibiting TNFα signaling with adalimumab on FLS isolated from synovial fluid of patients with JIA. Synovial fluid samples were selected from 41 patients in our repository. Of these samples, 23 were diagnosed with persistent oligoarticular JIA and 18 were diagnosed with extended oligoarticular JIA. All samples were taken prior to patients extending to a polyarticular course, or what we termed extended-to-be (ETB), and were on no medications or nonsteroidal anti-inflammatory drugs (NSAIDs) only at the time of arthrocentesis. For cell studies, FLS were isolated from synovial fluid and treated with adalimumab for 24h. Protein antibody arrays were performed by RayBiotech, Inc. according to their protocols. In persistent FLS, TNFα (fold change [FC] = 1.2 p = 0.001), TGFβ (FC = 1.5 p = 0.001), lymphotoxin alpha (LTα) (FC = 4.3 p = 0.015), soluble tumor necrosis factor receptor1 (sTNFRI) (FC = 5.1 p = 0.008), and soluble tumor necrosis factor receptor2 (sTNFRII) (FC = 3.8 p = 0.025) were significantly elevated in adalimumab treated cells compared to untreated cells. In ETB FLS, TNFα was significantly elevated (FC = 1.04 p = 0.023) while TGFβ (FC = 1.03 p = 0.037) was significantly decreased in adalimumab-treated cells compared to untreated cells. This data suggests that, after only 24h, adalimumab is effective at decreasing inflammation that occurs downstream of initial TNFα signaling in extended-to-be fibroblast-like synoviocytes.

Biological Agent Switching in Patients With Juvenile Idiopathic Arthritis: A Tertiary Center Experience.

The purpose of this study is to investigate the causes and outcomes of switching biological agents in juvenile idiopathic arthritis (JIA) patients using biological agents and compare the characteristics of patients whose biological agents are switched and those whose are not. This medical records review study was conducted with 128 patients who were diagnosed with JIA at our clinic between January 2009 and January 2022 and were receiving biologic agents. Factors affecting the biologic agent switching were investigated. The JIA subtype with the most frequent switching in biological agents was systemic JIA (n = 13, 40.6%). Systemic JIA was followed by rheumatoid factor-negative polyarticular JIA and persistent oligoarticular JIA with 5 patients (15.6%), extended oligoarticular JIA and enthesitis-related JIA with 3 patients (9.3%), rheumatoid factor-positive polyarticular JIA with 2 patients (6.2%), and undifferentiated JIA with 1 patient (3.1%). Among the patients, 32 (25%) patients had their biological agent switched once, and 5 (3.9%) had theirs switched twice. The most frequently used biological agent was etanercept (n = 76, 59.3%), whereas the most frequently observed cases of biological agent switching were from an anti-TNF agent to another anti-TNF agent (40.6%). The reason for switching was unresponsiveness to the agent in 22 patients (68.8%), adverse effects in 6 patients (18.7%), drug intolerance in 1 patient (3.1%), and other reasons in 3 patients (9.3%). The most frequently used biological agent was etanercept; the most frequent cases of biological agents switching were from an anti-TNF agent to another anti-TNF agent.

Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach

BackgroundJuvenile idiopathic arthritis constitutes a significant cause of disability and quality of life impairment in pediatric and adult patients. The aim of this study was to ascertain clinical remission (CR) and subsequent relapse in juvenile idiopathic arthritis (JIA) patients, according to therapeutic approach and JIA subtype. Evidence in literature regarding its predictors is scarce.MethodsWe conducted an observational, ambispective study. Patients diagnosed of JIA, treated with synthetic and/or biologic disease modifying antirheumatic drugs (DMARD) were included and followed-up to December 31st, 2015. Primary outcome was clinical remission defined by Wallace criteria, both on and off medication. In order to ascertain CR according to therapeutic approach, DMARD treatments were divided in four groups: 1) synthetic DMARD (sDMARD) alone, 2) sDMARD combined with another sDMARD, 3) sDMARD combined with biologic DMARD (bDMARD), and 4) bDMARD alone.ResultsA total of 206 patients who received DMARD treatment were included. At the time the follow-up was completed, 70% of the patients in the cohort had attained CR at least once (144 out of 206), and 29% were in clinical remission off medication (59 out of 206).According to treatment group, CR was more frequently observed in patients treated with synthetic DMARD alone (53%). Within this group, CR was associated with female sex, oligoarticular persistent subtypes, ANA positivity, Methotrexate treatment and absence of HLA B27, comorbidities and DMARD toxicity. 124 DMARD treatments (62%) were withdrawn, 64% of which relapsed. Lower relapse rates were observed in those patients with persistent oligoarticular JIA (93%) when DMARD dose was tapered before withdrawal (77%).ConclusionsMore than two thirds of JIA patients attained CR along the 9 years of follow-up, and nearly one third achieved CR off medication. Females with early JIA onset, lower active joint count and ANA positivity were the ones achieving and sustaining remission more frequently, especially when receiving synthetic DMARD alone and in the absence of HLA B27, comorbidities or previous DMARD toxicity.

Patterns of etanercept use in juvenile idiopathic arthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry

BackgroundWe aimed to characterize etanercept (ETN) use in juvenile idiopathic arthritis (JIA) patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.MethodsThe CARRA Registry is a convenience cohort of patients with paediatric onset rheumatic diseases, including JIA. JIA patients treated with ETN for whom the month and year of ETN initiation were available were included. Patterns of ETN and methotrexate (MTX) use were categorized as follows: combination therapy (ETN and MTX started concurrently), step-up therapy (MTX started first and ETN added later), switchers (MTX started and then stopped when or before ETN started), MTX add-on (ETN started first and MTX added later), and ETN only (no MTX use). Data were described using parametric and non-parametric statistics as appropriate.ResultsTwo thousand thirty-two of the five thousand six hundred forty-one patients with JIA met inclusion criteria (74% female, median age at diagnosis 6.0 years [interquartile range 2.0, 11.0]. Most patients (66.9%) were treated with a non-biologic disease modifying anti-rheumatic drug (DMARD), primarily MTX, prior to ETN. There was significant variability in patterns of MTX use prior to starting ETN. Step-up therapy was the most common approach. Only 34.0% of persistent oligoarticular JIA patients continued treatment with a non-biologic DMARD 3 months or more after ETN initiation. ETN persistence overall was 66.3, 49.4, and 37.3% at 24, 36 and 48 months respectively. ETN persistence among spondyloarthritis patients (enthesitis related arthritis and psoriatic JIA) varied by MTX initiation pattern, with higher ETN persistence rates in those who initiated combination therapy (68.9%) and switchers/ETN only (73.3%) patients compared to step-up (65.4%) and MTX add-on (51.1%) therapy.ConclusionThis study characterizes contemporary patterns of ETN use in the CARRA Registry. Treatment was largely in keeping with American College of Rheumatology guidelines.

OP0166 DISEASE ACTIVITY IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS AFTER SIMULTANEOUS PCV13 AND HIB VACCINATION: A COHORT STUDY

Background:The safety of vaccination of children with rheumatic diseases is determined not only by the risk of adverse events but also by the risk of exacerbation of the disease. The simultaneous administration of several vaccines can increase the likelihood of these events.Objectives:To evaluate the clinical and laboratory signs of disease activity in children with juvenile idiopathic arthritis (JIA) after simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) infections.Methods:We included hospitalized patients with JIA ages 2 through 18 without serious comorbidity, immunized with polysaccharide conjugate vaccines against pneumococcal (PCV13) and Hib infections. Vaccines were administered (0.5 ml each) concurrently subcutaneously into the deltoid area. In all children before and 3 weeks after vaccination, clinical (joints with active arthritis, uveitis activity) and laboratory signs (increased ESR, concentrations of highly sensitive C-reactive protein – hsCRP, and calprotectin) of JIA activity were assessed. Serum hsCRP and calprotectin were quantified by ELISA. The upper limit of the reference interval for hsCRP was considered (according to the manufacturer’s instructions) a value of 8.2 mg/L, for calprotectin – 2.9 μg/ml, and for ESR – > 10 mm/h.Results:The study included 430 patients with JIA (girls 60.9%), median (IQR) age – 11.1 years (7.3 to 14.4), onset of JIA – 4.7 years (2.4 to 8.6). Patients with persistent oligoarticular JIA numbered 149 (34.7%), polyarticular RF-negative – 148 (34.4%), systemic – 101 (23.4%), enthesitis-related – 20 (4.7%), and polyarticular RF-positive JIA – 12 (2.8%). Biologic disease-modifying antirheumatic drugs (DMARDs) were administered to 278 (64.7%), non-biologic DMARDs (mostly methotrexate) – 282 (65.6%), corticosteroids – 45 (10.5%), and NSAIDs – 18 (4.2%) patients. Three weeks after vaccination, out of 100 (23.3%) patients with initially active joints, signs of active arthritis remained in 96 patients, of which 16 patients had a decrease in the median (IQR) number of active joints by 4 (2 to 8). Among patients without active joints at baseline, signs of active arthritis were not subsequently detected. Before vaccination, 9 patients had uveitis in the exacerbation phase, 7 - in the subactive phase, and 41 - in the remission phase. After vaccination, exacerbation of uveitis persisted in 4 patients. There were no new cases of uveitis or its exacerbation. The dynamics of laboratory signs of JIA activity are presented in Table 1. Initially, the high concentration of calprotectin was found in 191 (44.4%) patients, and after vaccination – in 220 (51.2%) patients; the difference was 6.7% (95% CI 1.0 - 12.5); hsCRP - in 34 (7.9%) and 51 (11.9%) patients; the difference was 4.0% (95% CI 0.6 - 7.3); high ESR – in 76 (17.7%) and 41 (9.5%) patients; the difference was -8.1% (95% CI -11.6 to -4.7), respectively. An independent predictor of new cases of high concentration of hsCRP (n = 36), but not new cases of high concentration of calprotectin (n = 94), was the initial number of joints with active arthritis – odds ratio 2.37 (95% CI 1.14 - 4.93).Table 1.Laboratory signs of JIA activity after simultaneous administration of vaccines against pneumococcal (PCV13) and Hib-infectionsVariablesBaselineAfter 3 weeksRatio*p**Geometric mean (95% CI)Calprotectin, μg/ml2.93 (2.70 – 3.17)3.15 (2.92 – 3.40)1.08 (0.99 – 1.17)0.087hsCRP, mg/L0.69 (0.60 – 0.78)0.79 (0.69 – 0.90)1.15 (0.99 – 1.33)0.073ESR, mm/h4.4 (4.0 – 4.8)3.7 (3.4 – 4.0)0.84 (0.78 – 0.90)0.001Note. CI – confidence interval. * Ratios of paired observations (95% CI). ** P-value calculated in paired samples t-test.Conclusion:Simultaneous vaccination against pneumococcal (PCV13) and Hib-infections in children with JIA produced no negative dynamics of the traditional indicators of disease activity (joint activity, uveitis, high ESR). At the same time, 3 weeks after vaccination, an increase in the concentration of calprotectin and hsCRP was found in a small number of patients (<10%).Disclosure of Interests:None declared

Physical Fitness in Patients With Oligoarticular and Polyarticular Juvenile Idiopathic Arthritis Diagnosed in the Era of Biologics: A Controlled Cross-Sectional Study.

To perform a comprehensive evaluation of and identify correlates for physical fitness in consecutive patients with juvenile idiopathic arthritis (JIA) who have been diagnosed in the era of biologics and to compare the results with those obtained in healthy controls. The study cohort included 60 patients with JIA (50 girls) ages 10-16 years and 60 age- and sex-matched controls. The JIA group included 30 patients with persistent oligoarticular JIA and 30 patients with extended oligoarticular or polyarticular disease. Measures of physical fitness included cardiorespiratory fitness (CRF) by peak oxygen uptake (Vo2peak ) during a continuous graded treadmill exercise test, muscle strength by isokinetic and isometric knee and hand grip evaluations, and bone mineral density (BMD) and body composition by dual-energy x-ray absorptiometry. Physical activity was assessed by accelerometry. Forty-two percent of the patients were being treated with biologic drugs. Patients with JIA demonstrated lower muscle strength and total body BMD compared to controls, but there were no differences in CRF and body composition. Physical fitness was comparable between the persistent oligoarticular and extended oligoarticular/polyarticular-JIA groups. In patients with JIA, we identified associations between higher vigorous physical activity and higher CRF and muscle strength, but did not find any association between physical fitness and disease variables. In this cohort of patients with JIA, we found suboptimal muscle strength and BMD compared to controls, but no differences in CRF and body composition. Vigorous physical activities appeared important for optimizing muscle strength and CRF in patients with JIA; the importance of such activities should be highlighted in patient education.

Characteristics of synovial fluid in patients with juvenile idiopathic arthritis

Synovial fluid (SF) analysis is an important tool for the diagnosis of patients with juvenile idiopathic arthritis (JIA). A retrospective analysis was carried out of cytological features of SF samples obtained from patients with JIA during the period 2008-2016. A total of 102 SF samples from 59 patients were analysed. JIA was more common in females (66%). The most frequent form was persistent oligoarticular JIA (52.5%). The median age at onset was 5 years (IQR 2.4-11.8). SF usually showed an inflammatory pattern (median white blood cells count 11,757/mm3; IQR 4,543-18,800), with a predominance of polymorphonuclear (PMN) cells (61%; IQR 30-75). Eight patients (14%) had white blood cells counts of less than 2,000 cells/mm3, with predominance of mononuclear cells (80%), whereas 3 patients (5%) had white blood cells counts higher than 50,000 cells/mm3, with a predominance of PMN cells (90%). Synovial white blood cells count did not show significant differences among the different forms of JIA. The median synovial white blood cells count in ANA-positive patients was 20% lower than in ANA-negative (9,340 vs. 11,600/mm3; P=.23). The proportion of PMN increased with increasing levels of ESR (P<.001) and/or CRP (P=.03). No significant correlation was found between JADAS-10 and synovial white blood cells count (P=.4). SF obtained from different joints in simultaneous arthrocentesis showed a significant correlation P=.001). SF from JIA patients usually had inflammatory characteristics, although 19% of the patients showed white blood cells counts below 2,000cells/mm3 or higher than 50,000cells/mm3. SF cell count was non-significantly lower in ANA-positive patients, and the proportion of PMN increased with increasing levels of ESR/CRP.

Characteristics of synovial fluid in patients with juvenile idiopathic arthritis

IntroductionSynovial fluid (SF) analysis is an important tool for the diagnosis of patients with juvenile idiopathic arthritis (JIA). Patients and methodsA retrospective analysis was carried out of cytological features of SF samples obtained from patients with JIA during the period 2008–2016. ResultsA total of 102 SF samples from 59 patients were analysed. JIA was more common in females (66%). The most frequent form was persistent oligoarticular JIA (52.5%). The median age at onset was 5 years (IQR 2.4–11.8). SF usually showed an inflammatory pattern (median white blood cells count 11,757/mm3; IQR 4,543–18,800), with a predominance of polymorphonuclear (PMN) cells (61%; IQR 30–75). Eight patients (14%) had white blood cells counts of less than 2000cells/mm3, with predominance of mononuclear cells (80%), whereas 3 patients (5%) had white blood cells counts higher than 50,000cells/mm3, with a predominance of PMN cells (90%). Synovial white blood cells count did not show significant differences among the different forms of JIA. The median synovial white blood cells count in ANA-positive patients was 20% lower than in ANA-negative (9,340 vs. 11,600/mm3; P=.23). The proportion of PMN increased with increasing levels of ESR (P<.001) and/or CRP (P=.03). No significant correlation was found between JADAS-10 and synovial white blood cells count (P=.4). SF obtained from different joints in simultaneous arthrocentesis showed a significant correlation P=.001). ConclusionSF from JIA patients usually had inflammatory characteristics, although 19% of the patients showed white blood cells counts below 2000cells/mm3 or higher than 50,000cells/mm3. SF cell count was non-significantly lower in ANA-positive patients, and the proportion of PMN increased with increasing levels of ESR/CRP.

Significance of calgranulins (S100A8, S100A9 and S100A12), ferritin and toll-like receptor 4 in juvenile idiopathic arthritis children

Aim of the workTo evaluate role of calgranulins (S100A8, S100A9, and S100A12), ferritin and toll-like receptor 4 (TLR4) in juvenile idiopathic arthritis (JIA) children. Patients and methodsSera of 59 JIA Iraqi patients and 58 healthy-matched children were studied and serum levels of S100A8, S100A9, S100A12, ferritin and TLR4 assessed. Juvenile arthritis disease activity score-27 (JADAS27) was assessed. ResultsThe mean age of the patients was 10.1 ± 4.2 year; they were 40 females and 19 males with disease duration of 2.4 ± 2.6 years. The levels of S100A9 and ferritin were significantly increased in JIA patients compared to control (98 ± 63 vs. 65 ± 53 ng/ml; p = 0.004 and 57 ± 52 vs. 33 ± 31 ng/ml; p = 0.003, respectively), while S100A8, S100A12 and TLR4 levels showed no significant differences. Significant correlations were found; S100A8 with S100A9 (r = 0.27; p = 0.036) and TLR4 (r = 0.73; p = 0.001), S100A9 with TLR4 (r = 0.29; p = 0.026), and S100A12 with ferritin (r = 0.58; p = 0.001). S100A8, S100A9 and ferritin could significantly discriminate JIA from control (p = 0.035, p = 0.001, and p = 0.001, respectively). Corresponding sensitivities of S100A8, S100A9 and ferritin were 63%, 70% and 61%, and specificities were 60%, 66% and 60% at cutoff values of 28.3, 68.4 and 29.6 ng/ml, respectively. On multinomial logistic regression analysis, S100A9 and ferritin were significant predictors especially in those with positive C-reactive protein (CRP) and rheumatoid factor (RF), low JADAS27 and persistent oligoarthritis subtype. ConclusionsS100A8, S100A9 and ferritin were upregulated in sera of JIA patients. Their significance as predicting biomarkers of disease outcome was augmented, especially in CRP- and RF-seropositive, low JADAS27 and persistent oligoarticular JIA patients.

The necessity, efficacy and safety of biologics in juvenile idiopathic arthritis.

OBJECTIVE:Juvenile idiopathic arthritis (JIA) is the most common cause of chronic arthritis in children. Biologics have changed the faith of children with rheumatic diseases. The main objective of this study was to demonstrate the rate of usage, efficacy and safety of biologics in JIA subtypes.METHODS:This retrospective observational cohort study was conducted between May 2010 and September 2017. All children with the diagnosis of JIA and children under a biological agent treatment were recorded into the local registry system. Age, gender, JIA subtype, medications used, the clinical status of the patient, tuberculosis screening results, and side effects observed under biologics were retrieved from the registry.RESULTS:There were 405 patients with the diagnosis of JIA in the cohort. Biologics were used in 123 (30.3%) JIA patients. Subtype frequencies of JIA patients were as follows: persistent oligoarticular JIA (33.6%), enthesitis-related arthritis (29.2%), systemic JIA (13%), rheumatoid factor (RF)-negative polyarticular JIA (13%), extended oligoarticular JIA (4.2%), RF-positive polyarticular JIA (3.4%), psoriatic arthritis (1.8%) and unclassified arthritis (1.8%). The rate of biologic use was high in extended oligoarticular JIA (64.7% of the cases), RF-positive polyarticular JIA (57.1%), psoriatic arthritis (57.1%), RF-negative polyarticular JIA (41.5%), and in systemic JIA (39.6%). Enthesitis-related arthritis (27.1%), persistent oligoarticular JIA (17.6%) and unclassified arthritis (16.6%) patients were the cases that needed a biologic agent in the last order. At the last control, 78.9% of the cases were in remission, while 21.1% of them were active despite biologic treatment. Isoniazid prophylaxis was used in 30.8% of the patients. None of the patients developed active tuberculosis infection under prophylaxis. Adverse events were observed in 18.6% of patients under biologics as recurrent uncomplicated upper respiratory tract infections being the most common.CONCLUSION:Biologics are safe and effective treatment options in children with JIA. Most of the JIA patients with polyarticular involvement require biologics earlier in the disease course. The risk of tuberculosis infection seems not to be increased after appropriate screening and prophylaxis.

Prior to extension, Transcriptomes of fibroblast-like Synoviocytes from extended and Polyarticular juvenile idiopathic arthritis are indistinguishable

BackgroundOur intent was to identify differences between the transcriptome of fibroblast-like synoviocytes (FLS) in oligoarticular juvenile idiopathic arthritis (JIA) before extension when compared to persistent subtype of JIA, when the two are clinically indistinguishable. Additionally, we sought to determine if differences between the transcriptomes of FLS from extended-to-be and polyarticular course JIA could be detected. Our hypothesis was that intrinsic differences in the transcriptome of the FLS from extended-to-be JIA would distinguish them from persistent oligoarticular JIA, before the course is clinically apparent.MethodsGlobal gene expression was defined in cultured FLS from 6 controls, 12 JIA with persistent course, 7 JIA prior to extension (extended-to-be), 4 JIA with extended course and 6 polyarticular onset, using Affymetrix Human GeneChips 133plus2.0.ResultsBioconductor Linear Models for Microarray Analysis revealed 22 probesets with differential expression between persistent and extended-to-be FLS at 15% FDR, however only 2 probesets distinguished extended-to-be from extended and none distinguished extended-to-be and polyarticular at 15% FDR. Differences in extended and polyarticular gene expression profiles were not detected. Confirmation of select genes was done on the RNA level by RT-qPCR and on the protein level in synovial fluid by ELISA.ConclusionsThe transcriptome of FLS from extended-to-be juvenile idiopathic arthritis is distinct from persistent course before a clinical distinction can be made. Additionally, the transcriptome of extended-to-be and polyarticular course, including those who have already extended, are indistinguishable. These gene expression data suggest that FLS already reflect a polyarticular behavior early in disease course, suggesting that extended-to-be may be “latent polyarticular” at onset. These differences can be used to develop early biomarkers of disease course, allowing for better-informed treatment decisions.

Predictors of the response to etanercept in patients with juvenile idiopathic arthritis without systemic manifestations within 12 months: results of an open-label, prospective study conducted at the National Scientific and Practical Center of Children's Health, Russia

BackgroundThe aim of this study was to investigate the efficacy of etanercept treatment and to identify predictors of response to therapy within 12 months in patients with juvenile idiopathic arthritis (JIA) without systemic manifestations.MethodsA total of 197 juvenile patients were enrolled in this study. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the Wallace criteria, and the Juvenile Arthritis Disease Activity Score 71 (JADAS-71). Univariate and multivariate logistic regression analyses were performed to identify potential baseline factors associated with treatment response in different JIA categories.ResultsOne year after treatment initiation, 179 (90.9%) patients achieved ACRPedi30; 177 (89.8%) patients achieved ACRPedi50; 168 (85.3%) patients achieved ACRPedi70; and 135 (68.5%) patients achieved ACRPedi90 response. A total of 132 (67.0%) and 92 (46.7%) patients achieved inactive disease according to the Wallace criteria and the JADAS-71 cut-off point, respectively. Excellent response (achieving ACRPedi90 and clinically inactive disease according both to the Wallace criteria and the JADAS71 cut-off point) was associated with persistent oligoarticular JIA category, shorter disease duration before the start of etanercept, a lower number of DMARDs used before the introduction of etanercept, a lower number of joints with limited motion, and lower C-reactive protein at baseline. Poor response (failure to achieve ACR 70 or active disease according to both the Wallace criteria and JADAS71 even when ACR 70 was achieved) was associated with the polyarticular or enthesitis-related JIA categories, higher disease duration before the start of etanercept, and older age at disease onset.ConclusionAlmost half (45.7%) of the patients who initiated etanercept treatment achieved an excellent response (inactive disease and ACRPedi90) after 1 year. What may be novel is our finding that the response to etanercept therapy was strongly associated with the JIA category. The response to etanercept therapy was also associated with the disease duration before the start of etanercept treatment.

Juvenile idiopathic arthritis in relation to perinatal and maternal characteristics: a case control study

BackgroundExisting data on associations between maternal and early childhood exposures and juvenile idiopathic arthritis (JIA) risk is scant and inconsistent with previous studies showing potential role for prematurity, number of siblings and infections. We explored JIA and International League of Associations for Rheumatology (ILAR) JIA categories in relation to selected infant (birthweight, size-for-gestational-age, gestational age), and maternal (parity, delivery type, prior fetal loss) characteristics that may be markers for exposures related to two pathways (hygiene hypothesis, microchimerism) potentially associated with autoimmune disorder occurrence.MethodsA case–control analysis with 1,234 JIA cases and 5,993 birth year-matched controls was conducted. Exposure information was obtained from WA state birth certificates. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for associations with maternal and early life exposures for JIA and JIA categories.ResultsGreater maternal parity was associated with a decreased OR for JIA (most marked for persistent oligoarticular JIA, OR 0.32, 95% CI 0.15; 0.71, p for trend = 0.0001). Prior fetal loss (except for oligoarticular JIA) was associated with an increased OR for JIA. Prematurity was associated with increased risk of enthesitis related arthritis (OR 1.9, 95% CI: 1.3–2.9) and rheumatoid factor positive polyarticular JIA (OR 2.2, 95% CI: 1.0–4.8).ConclusionsWe observed associations of selected maternal factors with JIA, some of which varied across JIA categories. The findings of decreased ORs for JIA in relation to greater maternal parity may be consistent with the hygiene and microchimerism hypotheses. Future studies with biomarkers relevant to these hypotheses will help elucidate any associations.

Intra-articular injection in patients with juvenile idiopathic arthritis: factors associated with a good response

IntroductionIntra-articular injection of corticosteroids (IIC) for treatment of patients with juvenile idiopathic arthritis (JIA) is increasingly used in Pediatric Rheumatology. ObjectivesTo describe the clinical course of patients undergoing IIC in our Pediatric Rheumatology Unit. MethodsRetrospective study of patients with JIA undergoing IIC from January 2008 to December 2012, with a minimum follow-up of six months after the injection. Good response to IIC was set as the presence of inactivity on the infiltrated joint by at least six months. ResultsEighty-eight patients underwent a total of 165 IICs. Of these, 75% were girls and 35.2% had persistent oligoarticular JIA. The mean age at diagnosis was 6.8 years, and when IIC was carried out, 12.2 years. Regarding patients, younger age at diagnosis (p=0.037) and the occurrence of uveitis in the course of the disease (p=0.015) were associated with good response to IIC. From 165 IICs, 63% had a good response and joints remained inactive for a median of 18.1 months. The type of joint injection (p=0.001), lesser values stated in the overall visual analog scale by the physician (p=0.015) and by parents/patient (p=0.01) have been associated with a good response to IIC. Nine adverse events (5.4%) were observed. ConclusionIn our study, more than half of the joints showed a good response to IIC. Younger patients at diagnosis and uveitis during the course of the disease had good response to IIC. Knees, wrists and elbows were the joints that best responded to IIC. IIC proved to be a safe procedure.

Infiltração intra‐articular em pacientes com artrite idiopática juvenil: fatores associados à boa resposta

IntroductionIntra‐articular injection of corticosteroids (IIC) for treatment of patients with juvenile idiopathic arthritis (JIA) is increasingly used in Pediatric Rheumatology. ObjectivesTo describe the clinical course of patients undergoing IIC in our Pediatric Rheumatology Unit. MethodsRetrospective study of patients with JIA undergoing IIC from January 2008 to December 2012, with a minimum follow‐up of six months after the injection. Good response to IIC was set as the presence of inactivity on the infiltrated joint by at least six months. ResultsEighty‐eight patients underwent a total of 165 IICs. Of these, 75% were girls and 35.2% had persistent oligoarticular JIA. The mean age at diagnosis was 6.8 years, and when IIC was carried out, 12.2 years. Regarding patients, younger age at diagnosis (p=0.037) and the occurrence of uveitis in the course of the disease (p=0.015) were associated with good response to IIC. From 165 IICs, 63% had a good response and joints remained inactive for a median of 18.1 months. The type of joint injection (p=0.001), lesser values stated in the overall visual analogue scale by the physician (p=0.015) and by parents/patient (p=0.01) have been associated with a good response to IIC. Nine adverse events (5.4%) were observed. ConclusionIn our study, more than half of the joints showed a good response to IIC. Younger patients at diagnosis and uveitis during the course of the disease had good response to IIC. Knees, wrists and elbows were the joints that best responded to IIC. IIC proved to be a safe procedure.

Investigation of Complement-activating Pattern Recognition Molecules and Associated Enzymes as Possible Inflammatory Markers in Oligoarticular and Systemic Juvenile Idiopathic Arthritis.

The complement system plays a crucial role in the pathogenesis of inflammatory processes. The lectin pathway of the complement system is activated through the recognition of pathogens by soluble pattern recognition molecules (PRM), i.e., mannan-binding lectin (MBL), collectin-LK, and the ficolins. PRM are reportedly correlated to disease activity in rheumatoid arthritis (RA). The aim was to evaluate the pathogenic role of PRM in juvenile idiopathic arthritis (JIA). We measured MBL, M-ficolin, H-ficolin, MBL-associated serine proteases (MASP) 1, MASP-2, MASP-3, and 2 alternative splice products, MBL-associated protein (MAp) 44 and MAp19, in plasma and synovial fluid (SF) of children with persistent oligoarticular (n = 109 in plasma, n = 38 in SF) and systemic JIA (n = 19 in plasma, n = 11 in SF). The concentrations of the proteins were measured by in-house time-resolved immunofluorometric assays. We observed significantly higher levels of M-ficolin, MASP-1, MASP-2, and MASP-3 in plasma and SF from patients with systemic JIA compared with persistent oligoarticular JIA (p < 0.001). In paired samples of plasma and SF from 47 patients with oligoarticular and systemic JIA, we observed higher concentrations in plasma for both subtypes for 7 of the measured proteins while the reverse relationship was observed for MASP-3. M-ficolin and MASP-2 correlated to erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and platelet count (p < 0.001). M-ficolin was in addition related to the number of active joints and inversely related to hemoglobin levels. Our results point to plasma M-ficolin and MASP-2 as inflammatory markers in JIA. The levels of all proteins are higher in plasma than in SF, except for MASP-3, indicating that MASP-3 may be produced locally in joints.

PReS-FINAL-1018: Can the CD4/CD8β ratio be used as a predictive biomarker in extended-to-be oligoarticular JIA?

Predicting disease course in Juvenile Idiopathic Arthritis (JIA) is difficult. During the first 6 months of oligoarticular JIA (O-JIA) disease presents with 4 or fewer affected joints, however after 6 or more months severity might increase with more than 4 joints involved (extended O-JIA), or persist with 4 or fewer joints affected (persistent O-JIA). However patients do not show any clinical differences at onset making a decision on treatment strategy difficult before extension occurs. It has previously been shown that the CD4/CD8 T cell ratio in extended-to-be patients (samples before extension has occurred) is lower compared to those who persist (Hunter et al 2010), and thus might be a useful biomarker in predicting the course of disease. However measuring this cell ratio currently requires specialized expertise. To translate the measurement of the CD4/8 synovial T cell ratio as a biomarker a method is needed, which could be used in a wide range of hospital facilities, hence a real-time quantitative PCR (qPCR) method was tested.

PReS-FINAL-1004: Can the cd4/cd8β ratio be used as a predictive biomarker in extended-to-be oligoarticular JIA?

Predicting disease course in Juvenile Idiopathic Arthritis (JIA) is difficult. During the first 6 months of oligoarticular JIA (O-JIA) disease presents with 4 or fewer affected joints, however after 6 or more months severity might increase with more than 4 joints involved (extended O-JIA), or persist with 4 or fewer joints affected (persistent O-JIA). However patients do not show any clinical differences at onset making a decision on treatment strategy difficult before extension occurs. It has previously been shown that the CD4/CD8 T cell ratio in extended-to-be patients (samples before extension has occurred) is lower compared to those who persist (Hunter et al 2010), and thus might be a useful biomarker in predicting the course of disease. However measuring this cell ratio currently requires specialized expertise. To translate the measurement of the CD4/8 synovial T cell ratio as a biomarker a method is needed, which could be used in a wide range of hospital facilities, hence a real-time quantitative PCR (qPCR) method was tested.

Rationale, design and baseline data of a mixed methods study examining the clinical impact of a brief transition programme for young people with juvenile idiopathic arthritis: the DON'T RETARD project

ObjectivesTo describe (1) the content of a transition programme for young people with juvenile idiopathic arthritis (JIA) designed as a brief intervention, (2) the rationale and design of a mixed-methods...