Polyarticular Form Research Articles

Genetic insights into juvenile idiopathic arthritis derived from deep whole genome sequencing

Deep whole genome sequencing (WGS) allows for the comprehensive study of genetic landscapes at finer resolution than array based methods. We conducted deep WGS on children with the polyarticular form of juvenile idiopathic arthritis (JIA), using 2 independent cohorts to ascertain the sequencing fidelity. Genome wide SNP density analysis identified 18 SNP hotspots with comparison to the 1000 Genome Projects (1KGP) data. A subset of the genes adjacent to SNP hotspots showed statistically significant enrichment in immunological processes. Genes adjacent to indel hotspots were functionally related to G-protein coupled signaling pathways. Further analyses elucidated significantly more JIA SNPs with regulatory potential compared to 1KGP data. Furthermore, SNPs located within linkage disequibilium (LD) blocks containing previously identified JIA-associated SNPs demonstrated higher regulation potential compared to SNPs outside LD blocks. We also demonstrated enrichment of novel JIA variants in histone modification peaks and DNase hypersensitivity sites in B cells. This study greatly expands the number of genetic variants that may contribute to JIA and give us some clues into what may trigger this disease. To date, this study is the first deep WGS effort on children with JIA and provides useful genetic resources for research communities particularly in understanding JIA etiology.

Artritis reumatoide

ConceptRheumatoid arthritis is a systemic inflammatory disease of immune etiopathogenesis. EpidemiologyPresence of persistent synovitis in the joints. The pattern of joint involvement is usually symmetrical and erosive and can develop at any age. EtiopathogenesisIt is unknown, repeated exposure to certain environmental agents (tobacco and citrullination) has been related as a possible harmful mechanism, associated to a genetic predisposition to an immune response. Clinical manifestationsPatients present swelling of the joints, and polyarticular clinical forms usually appear, with multiple clinical involvement and progress patterns. Other extra-articular manifestations can develop, such as skin diseases, rheumatoid nodules, or pleuropulmonary or hematological manifestations. DiagnosisIt is conducted upon the presence of arthritis in association with radiographic and analytical data such as a positive rheumatoid factor and/or anti-citrullinated peptide antibodies. TreatmentThe course of the disease is poor if left untreated. Early treatment prevents structural progression. Some patients respond to traditional therapies with DMARDs (mostly methotrexate) and avoid further damage, but in many cases biological drugs are required, such as anti-TNF/anti-interleukin, or even anti-CD20, that have played an undisputed role in this disease.

Artritis psoriásica

IntroductionPsoriasic arthritis (PsA) is an inflammatory musculoskeletal disease that displays at least three of the following symptoms: psoriasis, nail dystrophy, dactylitis, negative rheumatoid factor or juxta-articular new bone formation. EpidemiologyPrevalence is estimated in 0.5% of the population, with an annual incidence of 4-8 cases per 100,000 inhabitants per year. It can develop at any age. It is a very heterogeneous disease regarding to the different forms of joint involvement. EtiopathogenesisMultiple theories have been established when it comes to its etiopathogenesis, so in a genetically predisposed individual the action of a harmful agent triggers a self-perpetuating inflammatory process over time, thus causing a structural lesion due to either the inflammation itself or to the associated repair processes. Clinical manifestationsPatients present joint swelling, enthesitis, dactylitis, nail/skin involvement. Aside from enthesopathies or spondylitis, other polyarticular clinical forms can appear which are similar to rheumatoid arthritis, also distal interphalangeal involvement and, more rarely, mutilans form. DiagnosisDiagnosis is mostly clinical since there are no pathognomonic analytical features. Prognosis and treatmentPrognosis is poor is left to its natural progress, though there are cases that remit spontaneously, it is common they require a tratment that avoids structural progress. Some clinical forms do not respond to traditional treatments with DMARDs and/or NSAIDs, thus requiring biological drugs.

Anti-cyclic citrullinated peptide antibodies in children with Juvenile Idiopathic Arthritis.

AimThe purpose of present study was to access the prevalence of anti-cyclic citrullinated peptide (anti-CCP) antibodies in children with Juvenile Idiopathic Arthritis (JIA), and to investigate the clinical significance and diagnostic value of the anti-CCP antibodies in correlation with age, sex & activity.MethodsThis case-control study was performed on 50 patients with JIA in addition to 40 sex and age-matched children as a control group. The participants were recruited from rheumatology Outpatient Clinic of Cairo University Specialized Pediatric Hospital. Patients were subjected to full history taking, clinical examination, routine laboratory investigations and x-rays on involved joints. Both patients and controls underwent assay of anti-CCP antibodies by AxSYM Anti-CCP IgG Microparticle Enzyme Immunoassay (MEIA) which is a semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in patients’ serum or plasma. Data were analyzed using Mann-Whitney U test, ANOVA, and independent-samples t-test by SPSS version 15.ResultsAnti-CCP positivity was identified amongst patients with JIA, particularly those JIA patients experiencing RF positive polyarticular disease onset. Above all, it is important that anti-CCP positivity and bone erosions, degree of joint damage, and ESR levels were significantly correlated.ConclusionAnti-CCP could be utilized as a valuable marker in the polyarticular form of JIA to direct early, and could be aggressive therapeutic intervention.

Association of TRAF1-C5 with risk of uveitis in juvenile idiopathic arthritis

ObjectivesNumerous single nucleotide polymorphisms (SNPs) have been associated with JIA, but few of these studies were replicated. We conducted a candidate-gene approach study to assess if some SNPs could be related to clinical subtypes or other clinical features of the juvenile idiopathic arthritis (JIA) such as the risk of uveitis, ANA positivity and the age at onset. MethodsSNPs in six genes were analysed: PTPN22, STAT4, TRAF1-C5, TGFbeta, TNFAIP3, and C12orf30. We retrospectively included 104 JIA patients, fulfilling the ILAR classification criteria. Association between SNPs and JIA clinical subtypes, the presence of ANA, risk of uveitis and age at onset was evaluated using a Chi2 test or a Fischer test. ResultsNo associations between different clinical subtypes as well as presence of ANA and the 6 SNPs were found. However, the AA genotype of TRAF1-C5 appeared associated in a subgroup of patients with uveitis in oligoarticular and polyarticular forms [OR 3.77 (95% CI: 1.1067, 12.8527); P=0.066]. Furthermore, AA TRAF1-C5 was significantly more frequent in antinuclear antibodies (ANA) positive patients presenting uveitis, compared to patients without uveitis and without ANA (P<0.05). ConclusionTRAF1-C5 genotype could identify JIA patients with a risk to develop uveitis especially in oligo and polyarticular forms and among ANA-positive children. Given the moderate size of our cohort, this association has to be confirmed in other studies.

The changing face of septic arthritis complicating rheumatoid arthritis in the era of biotherapies. Retrospective single-center study over 35 years

ObjectivesTo see whether the frequency and features of septic arthritis (SA) complicating rheumatoid arthritis (RA) have changed over the last 35years. MethodsThis retrospective single-center study included all patients hospitalized at the rheumatology department for SA bacteriologically documented by synovial fluid and/or blood culture samples. The periods 1979–2002 (before biotherapies) and 2003–2013 (the era of biotherapies) were compared. ResultsBetween 1979 and 2013, 64/514 (12.5%) SA presented with a RA – 21/157 (13.4%) in the 2003–2013 period and 43/357 (12.0%) in the 1979–2002 period. Over the past decade, median age of RA SA patients increased (61 vs. 68 years; P<0.02) and predominant gender became males (52% vs. 40%). The features of the RA remained unchanged: history (18 vs. 16years), rheumatoid factor (95% vs. 87%), and corticosteroids (91% vs. 81%). Over the last decade 24% (vs. 0; P<0.003) of the patients received a biologic DMARD: etanercept (n=2), adalimumab (n=1), rituximab (n=1), tocilizumab (n=1). Proportion of polyarticular infection had decreased strongly (9.5% vs. 37%; P<0.02). Proportion of Staphyloccus aureus infections remained stable, but there was a higher incidence of MRSA infections (31 vs. 6%; P<0.05). Blood cultures less often tested positive (29% vs. 47%; NS). Case fatality rate had fallen slightly in RA SA (5% vs. 9%; NS), but not in non-RA SA cases (7% vs. 6%; NS). ConclusionThis study brings reassuring findings – in the era of biotherapies, the rate of septic arthritis amongst patients with RA has not increased, and the most severe septic polyarticular forms are on the decline.

Current therapy of polyarticular forms of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in infancy and childhood. Approximately 20 % of patients with JIA suffer from the polyarticular form of the disease, which causes a substantial disease burden and long-term sequelae. Therapeutic approaches have used steroids and conventional disease modifying antirheumatic drugs (DMARD) but over the last decade new drugs have become available for the treatment of JIA, in particular biologic DMARD. This article summarizes the current therapy options for polyarticular JIA.

Рівень 25(OH)D в сироватці крові хворих із полісуглобовою формою ревматоїдного артриту та його залежність від деяких клінічно вагомих показників

Рівень 25(OH)D в сироватці крові хворих із полісуглобовою формою ревматоїдного артриту та його залежність від деяких клінічно вагомих показників

Anti-type II collagen antibodies detection and avidity in patients with oligoarticular and polyarticular forms of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) refers to a heterogeneous group of illnesses that have in common the occurrence of chronic joint inflammation in children younger than 16 years of age. The diagnosis is made only on clinical assessment. The identification of antibody markers could improve the early diagnosis, optimizing the clinical management of patients. Type II collagen is one potential autoantigen that has been implicated in the process of arthritis development. The aims of our study were to investigate the occurrence of anti-type II collagen antibodies and also to determine the avidity of the antibody–antigen binding. Ninety-six patients with oligoarticular or polyarticular JIA, 13 patients with ankylosing spondylitis (AS) and 61 healthy controls (HC) were tested for anti-type II collagen antibodies by ELISA and avidity ELISA. Sensitivity and specificity were determined by the receiver operating characteristic (ROC) curve analysis. Forty-two JIA patients (44%) were positive for antibodies against type II collagen. Its detection was significantly higher in JIA patients than in AS patients (p=0.006) and HCs (p<0.0001). Furthermore, anti-type II collagen antibody detection was significantly more frequent in patients with JIA of ≤6 months duration (p=0.0007). Antibodies displaying high avidity to type II collagen were associated with disease activity (p=0.004). This study demonstrates that antibodies against type II collagen are present in the serum of patients with oligoarticular and polyarticular JIA, being its presence more prevalent in patients with early disease. It also demonstrates that JIA patients with active disease present antibodies with high avidity against type II collagen.

Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis.

Association of juvenile spondyloarthritis (jSpA) with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in the development of the disease. To date, only a few studies have tried to find those associated genes by obtaining expression profiles, but with inconsistent results due to various patient selection criteria and methodology. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in highly homogeneous cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA) according to ILAR criteria. For the purposes of the research, total RNA was isolated from whole blood of 45 children with jSpA and known HLA genotype, 11 children with oligo- and polyarticular forms of JIA, as well as 12 age and sex matched control participants without diagnosis of inflammatory disease. DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatical analysis of retrieved data. Carefully selected differentially expressed genes where analyzed by qRT-PCR in all participants of the study. Microarray results and bioinformatical analysis revealed 745 differentially expressed genes involved in various inflammatory processes, while qRT-PCR analysis of selected genes confirmed data universality and specificity of expression profiles in jSpA patients. The present study indicates that jSpA could be a polygenic disease with a possible malfunction in antigen recognition and activation of immunological response, migration of inflammatory cells and regulation of the immune system. Among genes involved in these processes TLR4, NLRP3, CXCR4 and PTPN12 showed almost consistent expression in study patients diagnosed with jSpA. Those genes and their products could therefore potentially be used as novel biomarkers, possibly predictive of disease prognosis and response to therapy, or even as a target for new therapeutic approaches.

A successful treatment of juvenile idiopathic arthritis with rituximab: A report of two cases.

Juvenile idiopathic arthritis (JIA) is defined as arthritis of unknown cause that starts before 16 years of age and lasts at least 6 weeks. It is the most common chronic inflammatory disease in childhood and often persists through adulthood and can lead to severe disability. Biologics are an important therapeutic option for treating patients with JIA. The efficiency of rituximab has not been proven for this indication. Its use has rarely been reported in the literature. We report two new cases of severe and refractory polyarticular JIA with positive rheumatoid factor affecting two African females aged 17 and 18 years successfully treated with rituximab. According to our experience, the use of rituximab in the treatment of JIA, especially in severe polyarticular forms with positive rheumatoid factor, might be a good alternative. Larger therapeutic trials should be conducted in this direction in order to prove the effectiveness of this biotherapy for this indication.

Polyarticular juvenile idiopathic arthritis - epidemiology and management approaches.

Juvenile idiopathic arthritis (JIA) is a group of disorders characterized by arthritis persisting for at least 6 weeks with onset before the age of 16 years. Within this cluster of conditions, the polyarticular form (involving more than four joints within the first 6 months) is further divided based on the presence of rheumatoid factor. Children with polyarticular JIA pose unique diagnostic and therapeutic challenges compared to children with involvement of fewer joints. Polyarticular JIA patients tend to have a more refractory course and therefore are at increased risk for joint damage, resulting in poorer functional outcomes and decreased quality of life. Although the ability to treat this disorder continues to improve, especially with the advent of biologic agents, there is still much about the epidemiology and pathogenesis of polyarticular JIA that is unknown. The epidemiology of polyarticular JIA varies worldwide with a vast difference in reported cases between different global regions as well as within individual countries. Several genetic risk loci have been identified conferring increased susceptibility to JIA, many within the human leukocyte antigen region. Beyond the genome, environmental factors also seem to contribute to the etiology of polyarticular JIA. This review article will focus on the epidemiology and current treatments of polyarticular JIA and briefly discuss genetic and environmental influences on the pathogenesis of JIA as well as new and emerging therapies.

Understanding the biology and use of TNF therapy in jia-clinical outcomes

Treatment with anti-TNF therapies (anti-TNF) for polyarticular forms (extended oligo, Poly RF +/-) of JIA (PF-JIA) results in >50% demonstrating clinical inactive disease (CID).

AB0884 The Factors Affecting Bone Mineral Content in Patients with Juvenile Idiopathic Arthritis

ObjectivesTo determine the factors influencing bone mineral content in patients with juvenile idiopathic arthritis.MethodsA cross sectional studyin patientswith juvenile idiopathic arthritis (JIA) according to the International League of Association of...

SAT0410 Determinants of Hypertension in Patients with Psoriatic Arthritis

BackgroundSeveral studies have found a higher rate of hypertension among patients with psoriasis and psoriatic arthritis (PsA) versus the general population. This frequency may be even higher in patients with...

AB0882 To Determine the Factors Influencing the Lean Body Mass in Patients with Juvenile Idiopathic Arthritis

ObjectivesTo determine the factors influencing the lean body mass in patients with juvenile idiopathic arthritis.MethodsA cross sectional study in patients with juvenile idiopathic arthritis (JIA) according to the International League...

AB0885 Anti-Cyclic Citrullinated Peptide (ANTI-CCP) Antibodies in Polyarticular Juvenile Idiopathic Arthritis at Adulthood

BackgroundSeveral studies have already focused on anti-cyclic citrullinated peptide (anti-CCP) antibodies in juvenile idiopathic arthritis (JIA). Results of these studies showed that anti-CCP were associated with polyarticular sub-type (pJIA) and...

A12: The Role of Serum S100A12 Protein Levels in Disease Flare After Withdrawal of Anti‐tumor Necrosis Factor Therapy in Polyarticular Forms of Juvenile Idiopathic Arthritis

Background/Purpose:Anti‐TNF therapy for polyarticular forms (extended oligo‐, rheumatoid factor +/− polyarthritis) of JIA (PF‐JIA) results in up to 50% of patients (pts) demonstrating clinically inactive disease (CID). This study determined the pattern of serum S100A12 levels at the time of withdrawal of anti‐TNF therapy.Methods:In 16 centers, 137 pts with PF‐JIA in CID on anti‐TNF therapy were enrolled and followed for at least 14 months (mos). During the first 6 study mos pts were maintained on anti‐TNF therapy and if CID was maintained, then anti‐TNF therapy was stopped. Background medications were stable. S100A12 levels were obtained at the time of anti‐TNF withdrawal. The primary outcome was disease “flare” defined by worsening of ≥30% in ≥ 3 of the 6 core set variables, with no more than 1 improving by ≥30%. Parameters had to increase by at least the following amounts: MD and parent globals by 2 units, active and limited joints by 2, CHAQ by 0.125 and ESR from normal to abnormal.Results:24 pts failed to maintain CID in the first 6 study mos and 7 pts were discontinued from the study for other reasons. 106 pts were available for this analysis of whom 39 (37%) experienced flare. The S100A12 levels at time of anti‐TNF withdrawal did not differ significantly in regards to JIA type, presence of ANA, MTX co‐therapy, or type of anti‐TNF therapy and did not correlate with previous duration of CID. Globally, S100A12 at the time of withdrawal did not differ significantly according to disease flare (flare 73 +/− 117 ng/ml, no flare 80 +/− 220 ng/ml) (median ++/− standard deviation). Receiver‐operating curve (ROC) analysis computing S100A12 at time of anti‐TNF withdrawal against flare for the entire study period demonstrated an area‐under‐the‐curve (AUC) of 0.51, 95% confidence interval (CI) 0.39–0.62, for prediction of flare within 60 days AUC 0.66, 95% CI 0.56–0.75, for prediction of flare within 90 days AUC 0.64, 95% CI 0.54–0.74 and for prediction of flare within 120 days AUC 0.54, 95% CI 0.44–0.64. The S100A12 level at time of withdrawal correlated inversely with the time to flare (Spearman rank correlation = −0.34, p = 0.05). Flares occurred earlier in pts with predefined high (&gt;120 ng/ml) vs. low (≤120 ng/ml). S100A12 levels at time of withdrawal among pts who flared (median time to flare 36 vs. 114 days, p = 0.02). The overall flare rate in patients with high vs. low S100A12 levels at time of withdrawal was 35% vs. 38%, respectively. Kaplan‐Meier analysis of disease flare in pts with high vs. low S100A12 levels at time of withdrawal also demonstrated a trend towards earlier disease flare in pts with high S100A12 levels (log rank test significance 0.07).Conclusion:In this prospective study, a substantial proportion of pts with PF‐JIA experienced disease flare after anti‐TNF withdrawal. Serum S100A12 levels at time of anti‐TNF withdrawal did not differ between pts subsequently experiencing disease flare and those not experiencing flare throughout the entire study period. However, pts with high S100A12 levels (&gt;120 ng/ml) experienced earlier disease flare.

A68: The Role of Serum S100A12 Protein Levels in Maintaining Inactive Disease on Anti‐tumor Necrosis Factor Therapy in Polyarticular Forms of Juvenile Idiopathic Arthritis

Background/Purpose:Treatment with anti‐TNF therapies for polyarticular forms (extended oligoarthritis, rheumatoid factor [RF] +/− polyarthritis) of JIA (PF‐JIA) results in up to 50% of patients (pts) demonstrating clinically inactive disease (CID). Serum S100A12 protein levels have been demonstrated to predict failure to maintain CID after withdrawal of methotrexate (MTX). This study determined the pattern of baseline serum S100A12 levels during CID on anti‐TNF therapy.Methods:In 16 centers, 137 pts with PF‐JIA in CID on anti‐TNF therapy were enrolled. During the first 6 study months patients were maintained on anti‐TNF therapy and monitored. If CID was maintained for first 6 study months, then anti‐TNF therapy was stopped. Pts were followed for up to 14 mos total or until loss of CID on anti‐TNF therapy or until flare off anti‐TNF therapy, whichever came first. Background medications were stable throughout the study. Blood for serum S100A12 measurement was drawn at study enrollment. S100A12 measurements were obtained via a validated ELISA. The secondary outcome of this part of the analysis was failure to maintain CID during the first 6 study months.Results:7 pts were discontinued from the study for reasons other than inability to maintain CID and 130 patients were available for analysis. 24 pts failed to maintain CID during the first 6 study months. Demographic and clinical details are reported elsewhere during this conference. Baseline S100A12 levels did not differ significantly according to sex (female 96 +/− 229 ng/ml, male 66 +/− 144 ng/ml), JIA subtype (extended oligo 91 +/− 199 ng/ml, poly RF‐ 93 +/− 219 ng/ml, poly RF+ 114 +/− 157 ng/ml) presence of ANA (positive 83 +/− 174 ng/ml, negative 96 +/− 240 ng/ml), MTX co‐therapy (yes 84 +/− 259 ng/ml, no 95 +/− 167 ng/ml) or type of anti‐TNF therapy (adalimumab 114 +/− 140 ng/ml, etanercept 90 +/− 214 ng/ml, infliximab 120 +/− 330 ng/ml) (values given as median +/− standard deviation) and did not correlate with duration of previous duration of inactive disease (r = −0,06). Globally, S100A12 did not differ significantly according to failure to maintain CID (failure to maintain CID 100 +/− 188 ng/ml, maintaining CID 93 +/− 216 ng/ml). Based on a predefined normal level of S100A12 of &lt;120 ng/ml, 87 (66%) of patients demonstrated normal S100A12 levels and 43 (33%) of patients demonstrated elevated S100A12 levels. However, receiveroperating curve analysis computing baseline S100A12 against failure to maintain CID demonstrated an areaunder‐the‐curve of 0,47 (95% confidence interval 0.33–0.62).Conclusion:In this prospective multicenter study, baseline S100A12 levels in pts with PF‐JIA were elevated in a substantial proportion of pts but did not differ among groups according to multiple parameters. Serum S100A12 did not predict failure to maintain CID.

A20: Understanding the Use and Biology of TNF Therapy in JIA—Clinical Outcomes

Background/Purpose:Treatment with anti‐TNF therapies (anti‐TNF) for polyarticular forms (extended oligo, Poly RF +/−) of JIA (PF‐JIA) results in &gt;50% demonstrating clinically inactive disease (CID). The aims of this study were to determine the frequency, timing and predictors of flare upon withdrawal of anti‐TNF in PF‐JIA in CID.Methods:In 16 centers 137 children with PF‐JIA in CID on anti‐TNF were enrolled and followed for ≥14 mos. If CID was maintained for the first 6 study mos, then anti‐TNF was stopped. The primary outcome variable was a validated definition of disease flare within 8 months after stopping anti‐TNF. Background meds were stable. Blood for S100, DEK, DNA and RNA was drawn for current and future biomarker and genetic studies.Results:The study population included 18 (13%) extended oligarticular, 17 (12%) RF+ Poly and 102 (74%) RF‐ Poly JIA patients. At enrollment, age (mean/median/range) was 11.3/11.6/3.4–20.1 yrs; disease duration was 5.0/4.1/0.6–18.6 years; 103 (75%) were females and 64 (47%) were ANA+. Duration of CID at baseline was 1.2/0.5/1 day–12.1 yrs. Anti‐TNF was etanercept in 106 (77%), 25 (18%) adalimumab and 6 (5%) infliximab. 40% were on MTX at baseline (mean/median dose 0.4/0.4 mg/kg/week). Other meds: 1 leflunomide, 2 hydroxychloroquine, and 1 prednisolone.31 (23%) subjects were discontinued from the study in the first 6 mos: 23 (17%) due to loss of CID, 5 (4%) med noncompliance, 2 (1%) moved/LTF, 1 (1%) ILAR subtype changed (oligo to psoriatic). For the extended oligo, Poly RF− and Poly RF+ categories 94%, 82% and 60%, respectively, maintained CID for the first 6 months (c2 6.7, p 0.03). ANA status, MTX use, and type of anti‐TNF were not associated with the ability to maintain CID (c2 p values 0.48, 0.14, and 0.75, respectively).106 (77%) subjects maintained CID for the first 6 months and stopped anti‐TNF as per protocol. 67/106 (63%) maintained CID for ≥8 mos off anti‐TNF while 39 (37%) flared. Time without flaring after stopping anti‐TNF therapy was duration from the month 6 visit to the last study visit (mean/median/range for duration of followup was 249/250/126–322 days). The mean/median/range for time to flare was 108/105/7–271 days. Time to flare (days) for etanercept was 105/105/7–271, adalimumab 119/120/28–238 and infliximab 28/28/28. Flare was seen in 47% (8/17) extended oligo, 37% (30/80) poly RF– and 11% (1/9) poly RF+ ((c2 p‐value 0.19). In those on background MTX, 33% (13/40) flared at a mean of 90 days, while those not on background MTX, 39% (26/66) flared at a mean of 113 days ((c2 p‐value 0.48). Using univariate analysis of variance, only weak correlations of MTX dose, disease duration, and CID duration with flare/no flare were seen (Spearman correlations −0.03, −0.17, −0.19, respectively).Conclusion:In this prospective multicenter study, 77% of the PF‐JIA patients were able to maintain CID for the first 6 months on anti‐TNF. Discontinuation of anti‐TNF in PR‐JIA (who have demonstrated on average 1.8 years of CID) resulted in a flare rate of 37% within 8 mos. Clinical parameters had only minimal predictive ability. Ongoing work includes biomarker identification and continued follow‐up of the cohort.