Wallace Criteria Research Articles

The epigenetic determinants for systemic juvenile idiopathic arthritis phenotyping and treatment response

BackgroundDetermining the role of epigenetics in systemic juvenile idiopathic arthritis (SJIA) provides an opportunity to explore previously unrecognized disease pathways and new therapeutic targets.AimWe aimed to identify the clinical significance of microRNAs (miRNA-26a, miRNA-223) in SJIA.Materials and methodsThis cross-sectional study was conducted on a group of children with SJIA attending to pediatric rheumatology clinic, at Mansoura University Children’s Hospital (MUCH) from December 2021 to November 2022. Patient demographics, and clinical, and laboratory data were collected with the measurement of microRNAs by quantitative real-time PCR. The Mann–Whitney, Kruskal–Wallis, and Spearman correlation tests were used for variable comparison and correlations, besides the receiver operating characteristic (ROC) curve for microRNAs disease activity and treatment non-response discrimination.ResultsForty patients were included in the study. On comparison of miRNA-26a, and miRNA-223 levels to the clinical, assessment measures, and laboratory features, miRNA-26a was statistically higher in cases with systemic manifestations versus those without. Similarly, it was higher in children who did not fulfill the Wallace criteria for inactive disease and the American College of Rheumatology (ACR) 70 criteria for treatment response. Meanwhile, miRNA-223 was not statistically different between cases regarding the studied parameters. The best cut-off value for systemic juvenile arthritis disease activity score-10 (sJADAS-10) and the ability of miRNA-26a, and miRNA-223 to discriminate disease activity and treatment non-response were determined by the (ROC) curve.ConclusionThe significant association of miRNA-26a with SJIA features points out that this molecule may be preferentially assessed in SJIA disease activity and treatment non-response discrimination.

Associations of C reactive protein to albumin ratio, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio with disease activity in patients with juvenile idiopathic arthritis

IntroductionRecent works in the scientific literature reported the role of C reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as biomarkers of disease activity in rheumatic diseases.ObjectivesTo investigate the role of CAR, PLR and NLR as potential markers of disease activity in children with non-systemic JIA (nsJIA) and their correlation with the risk of persistent disease activity of flare during follow up.MethodsOur prospective, cross-sectional study involved 130 nsJIA patients (74 with active disease and 56 with inactive disease according to Wallace criteria) and 62 healthy controls. Demographic, clinical and laboratory data were collected at baseline (T0) and at 3 (T1), 6 (T2), 12 (T3) and 18 months (T4) during follow up. Disease activity was evaluated through Juvenile Arthritis Disease Activity Score (JADAS-27).ResultsAt baseline, CRP and CAR were higher in patients than in controls (p = 0.046), while no differences were found for NLR and PLR. However, there was no positive correlation between CAR, NLR, PLR and JADAS-27 in JIA patients. To better investigate the role of CAR, NLR and PLR as markers of disease activity, we used a generalized estimating equation (GEE) model, applied to all patients either with or without active disease. According to this analysis, CAR and NLR baseline levels were predictive of higher risk of disease activity at 6 months follow up (p < 0.001).ConclusionsCAR and NLR could indicate persistent disease activity in patients with JIA. Their predictive value could be increased by their combined use and by the observation of their trend during follow up, since increasing CAR values over time could predict a disease flare in the brief time.

Relapses of juvenile idiopathic arthritis in adulthood: A monocentric experience.

Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care. We conducted a retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression. Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse. In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.

P098 Anti-adalimumab antibodies are associated with active Juvenile Idiopathic Arthritis

Abstract Background/Aims Biologics have been used widely in the UK to treat Juvenile Idiopathic Arthritis (JIA) for over two decades. As this population has aged and switched biologics, there has been a growth in the cohort of patients who have switched through a greater number of biologics, consequently having fewer therapeutic options available. Our group has recently published data suggesting adalimumab has a greater drug survival compared to etanercept and infliximab. As part of our further investigation, we examined the relationship between adalimumab antibodies (AAA) and drug levels, stratified by disease activity (remission vs. active disease). Methods We conducted a retrospective observational study among patients with JIA and measured adalimumab drug levels and AAAs. The key metrics measured were AAAs (AU/L) and adalimumab drug levels (mg/mL). Disease remission was determined using standard Wallace criteria.The differences between the active and remission groups were examined with the Mann-Whitney U test. Results Among our cohort of 293 JIA patients receiving adalimumab, 179 had recorded adalimumab levels and AAAs. In 146 of these patients, we were able to measure disease activity, which was stratified into two distinct categories: Remission (N = 96) and Active (N = 50) according to Wallace criteria. Within our cohort of patients, there was a significant difference in both adalimumab drug levels, (P = 0.004) and AAAs (P = 0.00009) among those with active disease when compared to those in remission. Specifically, those with active disease exhibited a higher geometric mean AAA of 156.89 AU/L [95% CIs (95% confidence intervals) 129.65-189.85] when compared to those in remission with a mean of 65.25 AU/L (95% CI 41.10-103.58). The median AAA levels in those with active disease was 91 AU/L (IQR 0-200), compared with 0 (IQR 0-12.5) among those in remission. With respect to adalimumab drug levels, the geometric mean in patients with active disease was 7.27 mg/mL (95% CI 5.15-10.26) compared with 8.55 mg/mL (95% CI 7.26, 10.07) for patients in remission. The median drug level in the active group was 2.3 mg/ml (IQR 0-11.9) when compared with 9.4 mg/ml (IQR 3.8-13.1) in the remission group. Conclusion Various studies have demonstrated that the presence of AAAs is associated with secondary failure in JIA and other rheumatic diseases. However, the precise relationship between AAAs, adalimumab drug concentration and disease activity are yet to be elucidated, thus their regular monitoring is not currently part of guidelines or routine clinical practice.To our knowledge this is the largest single-centered cross-sectional study investigating the relationship of AAAs and remission state in JIA.Our study demonstrates that not only are higher AAAs associated with lower drug concentration, but that this is further associated with active disease. Disclosure M.W. Carrim: None. D. Sen: None. M. Shipa: None. C. Fisher: None. T. AlSulaim: None. A. Bouraoui: None. M. Leandro: None. C. Ciurtin: None. J. Glanville: None.

The importance of ultrasound examination in care of juvenile idiopathic arthritis patients: 9 months follow-up study.

Juvenile idiopathic arthritis (JIA) is a group of rare musculoskeletal disorders with chronic inflammation of joints, typically manifesting before the age of 16 years. The assessment of disease activity remains pivotal in JIA treatment decisions, particularly during clinical remission. While musculoskeletal ultrasound (MSUS) has shown promise in detecting subclinical synovitis, longitudinal data on MSUS features in JIA remains limited. The aim of this study was to evaluate the prevalence of subclinical synovitis observed in MSUS over a follow-up period in JIA patients. Additionally, it sought to assess the consistency and correlation between clinical findings, standardized composite clinical score (JADAS10), and MSUS-detected synovitis during 9 months follow-up. a prospective single-center study was conducted, enrolling all consecutive JIA patients (excluding systemic JIA) seen at the study center in one year period. At three-months intervals over a 9 months period (M0, M3, M6 and M9), patients underwent clinical examination, laboratory tests, and MSUS assessment. Data on demographic characteristics, disease profile, and treatment were collected. Patients were categorized into active disease (ACT) or remission (REM) groups based on Wallace criteria and JADAS10 scores using previously validated thresholds. The ultrasound assessments adhered to the Outcome Measures in Rheumatology Clinical Trials (OMERACT) pediatric group, covering 40 joints, were performed by two ultrasonographers at every visit. Subclinical synovitis was defined as synovitis detected exclusively by MSUS. Spearman's correlation coefficients (rs) were used to evaluate the association between MSUS, clinical data, and outcome measures, such as active joint count (ACJ), patient's/parent's global assessment of disease activity (PaGA), physician's global assessment of disease activity (PhGA) and JADAS10. subclinical synovitis was evident in 5.2% of all joints and in 80.6% of the patients at baseline. During the follow-up period, signs of subclinical synovitis decreased to 3.8% of joints, however, the proportion of affected patients remained high (67.7%), with the majority in REM group. Despite the consistent strong correlation between PaGA and PhGA throughout the study (rs > 0.895; p < 0.001), both measures displayed moderate (rs = 0.647; p < 0.001) to weak (rs = 0.377; p = 0.04) correlations with MSUS findings. Notably, PaGA remained significantly correlated with MSUS at the M9 visit (rs = 0.377, p = 0.04), while PhGA showed no correlation (p = 0.094). The study results indicate the persistence of subclinical inflammation detected by MSUS in a significant proportion of JIA patients, even during clinical remission. Moreover, the findings suggest that conventional measurements of JIA activity may be insufficient for assessing patients in clinical remission.

A decade of progress in juvenile idiopathic arthritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry.

To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005-2010 and 2017-2021 inception cohorts. Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan-Meier survival analysis and multivariable Cox regression. The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for good health-related quality of life (≥9/10). Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient-reported outcomes were smaller than improvements in disease activity.

Can Whole-Body Magnetic Resonance Imaging Predict Relapse in Juvenile Idiopathic Arthritis? A Longitudinal Pilot Study.

To determine the utility of whole-body magnetic resonance imaging (WB MRI) to predict relapse in children with juvenile idiopathic arthritis (JIA) in clinical remission. Consecutive patients with JIA who fulfilled the Wallace criteria for remission were recruited into this longitudinal pilot study and underwent WB MRI. A radiological score was devised, incorporating synovitis, bone marrow edema, sacroiliitis, enthesitis, and bone erosions. Two readers independently scored the MR data sets. The same score was calculated for both knee joints individually and correlated with outcome for that joint. Score-based models incorporating clinical and laboratory variables were generated. Logistic regression analysis was done to determine predictors for relapse. Receiver operating characteristic curve was drawn for significant variables. Twenty-two children (median age, 12 years; interquartile range, 9.5-14.25 years) were included in the final analysis. At 24 months' follow-up, 15 joints in 5 children relapsed; knee was the most common site. Seven knee joints had disease relapse. On univariate analysis, synovitis and total score on WB MRI were significant predictors of relapse at follow-up, with odds ratios of 9.46 (bias-corrected 95% confidence interval, 3.07-29.13) and 2.8 (bias-corrected 95% confidence interval, 1.23-6.39) respectively. Two models, which included a higher number of joints involved at presentation and abrupt drug withdrawal strategy as predictor variables, were also statistically significant (odds ratio, approximately 1.9). On multivariate analysis of the predictors variables in models where p < 0.6, it was found that only synovitis score and total score were near statistical significance ( p = 0.06); no clinical or laboratory variables were significant. The areas under the receiver operating characteristic curve for relapse prediction were approximately 0.82, 0.87, 0.79, and 0.81 for synovitis score, total MRI score, and both models, respectively. Synovitis on WB MRI is the strongest independent predictor for disease relapse in children with JIA in remission.

The role of ultrasonography in assessing remission in juvenile idiopathic arthritis: a systematic review.

Musculoskeletal ultrasound (MSUS) is an important measurement tool in pediatric rheumatology as it detects subclinical disease activity and enables clinicians to treat patients during "the window of opportunity". However, the role of MSUS in assessing remission in JIA patients is not well-defined. This systematic review aimed to provide the most up-to-date published literature regarding the added value of MSUS in JIA patients in remission. This systematic review followed the preferred reporting items for systematic reviews guidelines. Original articles from PubMed and Scopus, published until February 7th 2022, and tackling the role of MSUS in JIA patients in remission were included. Eight studies met the inclusion criteria. They were published between 2011 and 2019 and included 356 children with JIA. Remission criteria were unanimous and relied on the Wallace criteria. Subclinical synovitis and Power Doppler signal (PD) were found in up to 84% and 33% of patients in remission, respectively. In most of the studies, predictors of future flares were abnormal MSUS findings at baseline particularly the presence of PD signal and patients without medication. Conclusion: Published data indicate that JIA children in remission may have abnormal MSUS findings including PD signal. The application of a specific scoring system for the pediatric joint may be helpful in homogenizing outcomes in future trials. Further studies on this matter are needed to ascertain the specific implication for each subset for a better holistic approach. What is Known: • In these recent years, significant progress has been made on building the evidence base for MSUS in pediatric rheumatology, particularly in juvenile idiopathic arthritis (JIA). • In the frame of the OMERACT ultrasound pediatric subtask force, standardized musculoskeletal US examination for the pediatric population was established. What is New: • Published data indicate that JIA children in remission may have abnormal MSUS findings including PD signal. The role of MSUS in assessing remission in JIA is still not well-defined. • The application of a specific scoring system for the pediatric joint may be helpful in homogenizing outcomes and comparing results.

Prevalence of Subclinical Activity by Ultrasound Examination in Mexican Children with Juvenile Idiopathic Arthritis in Remission

Background: Juvenile Idiopathic Arthritis (JIA) is a chronic disease that affects 0.6 - 1.9 /1,000 children. Persistent joint inflammation conditions cartilage damage and erosions. Recent studies have shown that clinical examination significantly underestimates joint inflammation, with ultrasound having a higher sensitivity. The aim of this study was determined the prevalence of subclinical synovitis by musculoskeletal ultrasound in Mexican children with JIA in remission. Methods: Cross-sectional study, patients with JIA in clinical remission based on the Wallace criteria were included, with and without pharmacological treatment, we also included a control group of healthy children. The evaluation was performed by a certified Rheumatologist in Pediatric Musculoskeletal Ultrasound by EULAR. Joints clinically examined were also evaluated following the standard guidelines. Results: A total of 37 JIA patients with clinical remission and 33 healthy children were evaluated (1260 joints scanned), subclinical activity was detected in 15/37 (40.5%) patients and none of healthy children; 14 patients were still on treatment (93.3%). The subclinical activity was detected by gray scale in 22/1260 (1.7%) or by power Doppler (PD) in 15/1260 (1.1%) joints, the knee was involved in 13/22 (59%) joints. The subtype mainly affected was the rheumatoid factor-positive (FR) polyarticular (33.3%), erosions were detected in three patients (8%). In the knee, we observed slight distention of the supra patellar recess, evidenced in 19/33 healthy children (57.5%), predominantly among children aged 4 to 8 years. When comparing the groups with or without subclinical synovitis, no statistically significant differences were found with regard to age, evolution time or acute phase reactants. Conclusions: Subclinical synovitis was detected in 40.5% of the patients in clinical remission using gray scale or by power Doppler, mainly on those who were still on treatment. The most affected subtype was the rheumatoid factor-positive polyarticular, the knees were the most frequent involved. In the healthy children, a slight distention of the supra patellar recess was observed in almost half of cases.

Prevalence of Subclinical Activity by Ultrasound Examination in Mexican Children with Juvenile Idiopathic Arthritis in Remission

Background: Juvenile Idiopathic Arthritis (JIA) is a chronic disease that affects 0.6 - 1.9 /1,000 children. Persistent joint inflammation conditions cartilage damage and erosions. Recent studies have shown that clinical examination significantly underestimates joint inflammation, with ultrasound having a higher sensitivity. The aim of this study was determined the prevalence of subclinical synovitis by musculoskeletal ultrasound in Mexican children with JIA in remission. Methods: Cross-sectional study, patients with JIA in clinical remission based on the Wallace criteria were included, with and without pharmacological treatment, we also included a control group of healthy children. The evaluation was performed by a certified Rheumatologist in Pediatric Musculoskeletal Ultrasound by EULAR. Joints clinically examined were also evaluated following the standard guidelines. Results: A total of 37 JIA patients with clinical remission and 33 healthy children were evaluated (1260 joints scanned), subclinical activity was detected in 15/37 (40.5%) patients and none of healthy children; 14 patients were still on treatment (93.3%). The subclinical activity was detected by gray scale in 22/1260 (1.7%) or by power Doppler (PD) in 15/1260 (1.1%) joints, the knee was involved in 13/22 (59%) joints. The subtype mainly affected was the rheumatoid factor-positive (FR) polyarticular (33.3%), erosions were detected in three patients (8%). In the knee, we observed slight distention of the supra patellar recess, evidenced in 19/33 healthy children (57.5%), predominantly among children aged 4 to 8 years. When comparing the groups with or without subclinical synovitis, no statistically significant differences were found with regard to age, evolution time or acute phase reactants. Conclusions: Subclinical synovitis was detected in 40.5% of the patients in clinical remission using gray scale or by power Doppler, mainly on those who were still on treatment. The most affected subtype was the rheumatoid factor-positive polyarticular, the knees were the most frequent involved. In the healthy children, a slight distention of the supra patellar recess was observed in almost half of cases.

Sacroiliitis at diagnosis as a protective predictor against disease flare after stopping medication: outcomes of a Southeast Asian enthesitis-related arthritis (ERA) longitudinal cohort.

To assess short- and long-term outcomes of ERA in a large monocentric cohort in Singapore. Children diagnosed with ERA according to ILAR criteria from 2002 to 2021 were recruited. Nonparametric statistics were used to describe the data. Outcomes were defined according to modified Wallace criteria, and probabilities and predictors were determined using Kaplan-Meier survival and logistic regression analyses. One hundred fifty-one ERA patients (male 86%; Chinese 81%) were included. The median age at onset was 11.9years (IQR: 9.4-13.9), and disease duration was 5.3years (IQR: 2.9-8.4). At diagnosis, 39% of the patients had sacroiliitis. HLA-B27 was positive in 83%, and biologics were used in 72% of the patients. Clinical inactive disease (CID) was achieved in 92% of the patients, of which 27% achieved within 6months. Sacroiliitis at diagnosis is an unfavorable predictor of early CID at 6months. Medication was discontinued in one-third of the patients. Favorable predictor of medication withdrawal includes male gender, while unfavorable predictors include positive HLA-B27 and ANA. Two-thirds of the patients with CID had at least one disease flare. Sacroiliitis at diagnosis is a protective predictor of flare after stopping medication. Despite a high proportion of ERA patients achieving CID, only one-third could stop medication with high rates of disease flare. Unfavorable predictors include older age at onset, HLA-B27, and ANA positivity. While sacroiliitis at diagnosis is a negative predictor of CID at 6months, it is associated with less disease flare after discontinuing medication.

Предикторы достижения ремиссии при терапии генно-инженерными биологическими препаратами (тоцилизумабом и канакинумабом) детей с системным ювенильным идиопатическим артритом: когортное исследование

Therapy with biologicals at the onset of systemic juvenile idiopathic arthritis (sJIA) ensures faster achievement of inactive disease or remission in more patients compared to standard treatment. Identification of predictors of early response to biologicals is necessary to increase treatment efficacy in children with sJIA. Objective. To develop a model for predicting treatment outcomes with different biologicals in sJIA patients. Materials and methods. We analyzed medical records of sJIA patients who received tocilizumab or canakinumab and were admitted to the Department of Rheumatology between July 2009 and February 2021. Predicted outcomes included inactive disease after 12 months of therapy with biologicals (according to C. Wallace criteria and JADAS71) and drug-free remission (without biologicals) for at least 6 months. Potential predictors comprised patient demographic and clinical characteristics, such as sJIA activity, CHAQ index, concomitant therapy, treatment outcomes after 1 and 3 months of therapy, etc. (115 parameters in total). Independent predictors were chosen using multivariate binary logistic regression. Results. This study included 250 patients receiving tocilizumab and 73 patients receiving canakinumab. After 12 months of tocilizumab therapy, 179 patients (76%) achieved inactive disease according to C. Wallace criteria and 170 patients (72%) achieved remission according to JADAS71 index. Drug-free remission (for at least 6 months without biologicals) was registered in 51 patients (20%) from the tocilizumab group. In the canakinumab group, inactive disease according to C. Wallace criteria, remission according to JADAS71, and drug-free remission were achieved in 58 (79%), 58 (79%), and 10 (14%) patients, respectively. Duration of morning stiffness at sJIA onset, dynamics of the duration of morning stiffness after 1 and 3 months of treatment, disease activity evaluated by a physician using the 100-mm visual analog scale (VAS) after one month of therapy, and patientreported overall well-being evaluated using VAS after 3 months of therapy were found to be the predictors of achieving remission according to C. Wallace criteria in the tocilizumab group. The following factors were significantly associated with remission according to JADAS71 index: duration of morning stiffness at sJIA onset and upon treatment initiation, VAS score evaluated by a physician after 1 and 3 months, and number of painful joints after 3 months. We also found several predictors of achieving drug-free remission, including lymphocyte count at disease onset, therapy with glucocorticoids (GCs) and its duration by the time of biological initiation, ESR upon treatment initiation, 50% improvement according to ACR pediatric criteria after 1 month, administration of systemic GCs after 1 month, ESR dynamics by 3 months, and number of joints with limited motion after 3 months. In the canakinumab group, the following factors were associated with remission according to C.Wallace criteria and JADAS71: duration of morning stiffness at treatment initiation, number of biologicals received in the past, 30% improvement according to pediatric ACR criteria after 1 month, and presence of joints with limited motion after 3 months; the predictors of drug-free remission included previous treatment with tocilizumab, number of active joints, and patient-reported overall well-being evaluated using VAS at treatment initiation, dynamics of the number of joints with active arthritis after 1 and 3 months, dynamics of JADAS71 after 1 month, lymphadenopathy after 1 month, and dynamics of patient-reported overall well-being after 3 months. Conclusion. Treatment in the past, characteristics of joint syndrome before and 1–3 months following treatment initiation, dynamics of laboratory parameters and VAS scores of disease activity (both patient-reported and physician-rated) were independent predictors of remission in sJIA patients during therapy with tocilizumab and canakinumab. Key words: systemic juvenile idiopathic arthritis, remission, predictors, biologicals, interleukin-1b inhibitor, interleukin-6 receptor inhibitor, tocilizumab, canakinumab

Serum calprotectin (S100A8/9), clinical and ultrasound assessment in patients with juvenile idiopathic arthritis.

To explore the association between serum S100A8/9 (calprotectin), clinical and ultrasound (US) assessment in juvenile idiopathic arthritis (JIA) patients. A total of 30 well-characterised consecutive patients (18 female) with non-systemic JIA and 20 age-matched healthy controls were included. Serum and plasma samples obtained the same day of the clinical and sonographical assessment were tested for calprotectin levels by ELISA. Clinical status was defined using Wallace criteria. Ultrasonographic B-mode and power Doppler (PD) assessment of 44 joints for each subject was performed. Clinically active disease was present in 14 patients, while 16 patients were active according to US evaluation. We found no differences in the serum/plasma calprotectin levels in clinically active disease group [29.6 (5.4-198.1) ng/ml; 12.6 (2.8-65.8) ng/ml] as compared with inactive disease group [24.8 (14.1-204.3); 12.7 (3.4-65.1)] (p=0.73; p=0.29). There was also no difference between US active disease [29.8 (5.4-204.3); 12.9 (2.8-65.8)] and US inactive disease [24.8 (12.1-197.1); 11.7 (3.4-44.2)] with regard to the serum/plasma calprotectin levels (p=0.83; p=1.0). Serum/plasma calprotectin levels correlated moderately with C-reactive protein (CRP) (Spearman r=0.44, p=0.01; Spearman r=0.56, p=0.0021). To our knowledge, this is the first study to simultaneously examine the correlation between serum/plasma calprotectin levels, clinical and US assessment in JIA. Calprotectin was not associated with the disease status in JIA patients with low number of active joints and its levels were moderately correlated with CRP. Our preliminary study needs to be extended with a larger number of patients.

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.

Experiences with IL-1 blockade in systemic juvenile idiopathic arthritis \u2013 data from the German AID-registry

BackgroundSystemic juvenile idiopathic arthritis (sJIA) is a complex disease with dysregulation of the innate immune system driven by cytokines. A major role is ascribed to interleukin-1β (IL-1β), supporting the autoinflammatory character of the disease and offering an effective blocking mechanism for treatment. Here we present clinical practice data from the German AID-registry for patients treated with IL-1 inhibition (IL-1i).MethodsIn 2009 a clinical and research consortium (AID-Net) was established, including an online AID-registry. Patients with documented sJIA diagnosis were identified. Data for this retrospective IL-1i study were recorded by 17 centers. Response to treatment was evaluated according to Wallace criteria and additionally by an own classifying clinical response system.ResultsIn 6 years, 202 patients with confirmed sJIA were recorded in the AID-registry. Out of these, 111 children received therapy with Anakinra (ANA) (n = 84, 39 f) and/or Canakinumab (CANA) (n = 27, 15 f) at a median age of 8.7 y (range 0.6–19.1). During the first 12 months 75/111 (ANA 55, CANA 20) patients were evaluated according to Wallace criteria (achievement of inactive disease 28/55 and 17/20, remission over 6 months under medication 13/55 and 7/20 cases). Over the whole period of time, clinical response was preserved in the majority of patients (ANA 54/80, CANA 20/27). Arthritis mostly persisted in polyarticular (PA) courses. During treatment with IL-1i concomitant medication could be tapered in about 15%. IL-1i was discontinued in 59/111 patients. 45 (15) adverse events (AE)s in ANA (CANA) treated patients (19.7 (26.6) AE/100 ANA (CANA) exposure years, 95%CI: 14.4–26.4 (14.9–43.9)) were reported.ConclusionIn a large cohort of sJIA patients from Germany, we can confirm an overall favorable clinical response to both available IL-1 blocking agents. IL-1i was well tolerated with acceptable safety and effectiveness in a real-life clinical setting.

Outcomes and predictors of juvenile idiopathic arthritis in Southeast Asia: a Singapore longitudinal study over a decade.

To assess short- and long-term outcomes and predictors of juvenile idiopathic arthritis (JIA) children treated with contemporary therapy and compare those with reports elsewhere. Children with JIA were recruited from our web-based REgistry for Childhood Onset Rheumatic Diseases (RECORD) from 1997 to 2015. Disease status was defined using modified Wallace criteria. Nonparametric statistics described the data. Kaplan-Meier survival and logistic regression analyses were used to estimate probabilities and to determine predictors of outcomes. A total of 251 children with JIA (62% males, 71% Chinese) were included. Median follow-up duration was 2.9years (range 0.1-17.5). Short-term clinical inactive disease (CID) was attained in 37% with 62% systemic JIA (sJIA) and 47% persistent oligoarthritis (oJIA). Methotrexate (OR 0.34) decreased but sJIA (OR 3.25) increased chance of attaining CID at 6months. Overall, 79% of patients achieved CID within 2years (sJIA 92%, the highest, and RF+ polyarthritis 50%, the lowest probability). Biologics were associated with CID attainment (OR 2.73). One-half of patients flare after CID, median 1.2years (IQR 0.71-1.97). Late CID achievement predicted flare (OR 2.15). Only 15% had clinical remission off medication (none RF+ polyarthritis and 7% ERA). Only 13% of patients had active arthritis as young adults and 22% had active arthritis at last visit. Despite high proportion of JIA patients attaining CID, only one-fourth could stop all medications for at least 1year. Persistent oJIA patients were less likely to achieve clinical remission on medication and ERA patients had the least chance stopping medications. One-tenth of patients had active arthritis as young adults. Key Points • Majority of Asian children with JIA attained inactive disease within 2years after diagnosis. • Outcome predictors were different from reports from the West. • Despite high inactive disease numbers, only one-in-four JIA patients discontinued treatment within 5years.

Subclinical cardiovascular risk signs in adults with juvenile idiopathic arthritis in sustained remission

BackgroundJuvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases of childhood that often persists into adulthood and can result in significant long-term morbidity. As a long lasting chronic inflammatory disease, concern has been raised regarding the risk of premature development of cardiovascular disease (CVD) in JIA. This study aims to determine whether adults with JIA in clinical remission display clinical and subclinical signs of CVD risk: inflammatory mediators, adipokines, endothelial dysfunction and oxidative stress markers.MethodsThis is a cross-sectional study including 25 patients diagnosed with JIA according to the International League of Associations for Rheumatology criteria (ILAR 2001) and 25 age- and sex-matched controls. Remission was determined by JADAS10 < 1 and according to Wallace criteria. The presence of traditional CVD risk factors was analyzed. An extensive clinical analysis including body mass index (BMI), lipid profile, homeostatic model assessment – insulin resistance (HOMA-IR) and arterial blood pressure was performed. Intima media thickness of the common carotid artery (CIMT) was measured as a marker of subclinical atherosclerosis. Several proinflammatory cytokines, molecules involved in the endothelial dysfunction, oxidative stress and adipokines were quantified on serum by ELISA and on peripheral blood mononuclear cells (PBMCs) by RT-PCR. In vitro studies were carried out in healthy PBMCs, adipocytes and endothelial cells which were treated with serum from JIA patients under sustained remission.ResultsMean duration of the disease was 13.47 ± 5.47 years. Mean age was 25.11 ± 7.21. Time in remission was 3.52 ± 3.33 years. Patients were in remission with no treatment (40%) and with treatments (60%). CVD risk factors and CIMT were similar in JIA patients and controls. However, cholesterol levels were significantly elevated in JIA patients. Levels of adipocytokines, oxidative stress and endothelial activation markers were elevated in serum and PBMCs from JIA patients. Serum of those JIA patients induced the activation of adipocytes, endothelial cells and healthy PBMCs.ConclusionsJIA adult patients in remission have subclinical signs of inflammation and CVD risk, showed by an increase in the levels of inflammatory cytokines, endothelial activation and oxidative stress markers and adipokines, molecules closely involved in the alteration of the vascular system.

Long-term outcomes and disease course of children with juvenile idiopathic arthritis in the ReACCh-Out cohort: a two-centre experience.

To assess long-term outcomes of children with JIA diagnosed in the biologic era. Chart review of patients prospectively enrolled in the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort at two Canadian centres. Inactive disease and remission were defined according to Wallace criteria. We included 247 of 254 (97%) eligible patients diagnosed 2005-10. At the last follow-up visit at a median age of 16.9 years, 47% were in remission off medications, 25% in remission on medications and 27% had active disease; 51% were on at least one anti-rheumatic medication (22% on biologics). Patients with systemic JIA had the highest frequency of remission off medications (70%) and patients with RF-positive polyarthritis had the lowest (18%) (P<0.05 by Fisher's exact test). Among 99 patients with oligoarthritis at enrolment, 14 (14%) had an oligoarthritis extended course. Forty-five patients (18%) had at least one erosion or joint space narrowing in X-rays or MRI, and two (0.8%) required joint replacement. Relative to historical cohorts, this study suggests a reduction in JIA permanent damage, a more favourable prognosis for systemic JIA and a lower progression to oligoarthritis extended category. However, in an era of biologic therapy, one in four patients with JIA still enter adulthood with active disease and one in two still on treatment.

Efficacy and safety of adalimumab as the first- and second-line biologic therapy for children with juvenile idiopathic arthritis under four years of age

BackgroundNew biologics developed to treat juvenile idiopathic arthritis (JIA) and the broadening range of indications for young children offer new drug switch options if the first-line treatment has proved ineffective. Nevertheless, the question regarding selection of the optimal medication depending on patients' characteristics and prior therapy still needs to be solved. Aim of the workTo evaluate the efficacy and safety of adalimumab (ADA) as the first and subsequent biologic drug in children under 4 years of age. Patients and methodsAnalysis was performed using the Research Center for Children’s Health registry data, including the prospective observational results involving children with JIA who had started ADA treatment between 2009 and 2012. Patients were allocated into the biologic-switcher (n = 8) and biologic-naïve (n = 17) groups according to prior treatment. The response to therapy was assessed using the ACR Pedi and the modified Wallace criteria. ResultsThe percentage of patients who had achieved ACR50/70/90 after 24-month therapy was 82.4/76.5/64.7% in the biologic-naïve and 62.5/50.0/37.5% in the biologic-switcher group. The percentages of patients who had achieved remission were comparable between the two groups (41.2 and 37.5%, respectively). 23 AEs occurred in 16 (64%) patients throughout the follow-up period. ADA was withdrawn from 6(24%) patients. One (5.9%) biologic-naïve patient and 2(25%) biologic-switchers discontinued treatment because of lack of efficacy. ConclusionsADA is efficacious and relatively safe in children younger than 4 years. However, ADA showed better efficacy in achieving ACR70/90 and maintaining the lowest disease activity at 24 months treatment in biologic-naïve patients.

The Effect of Morning Stiffness Duration on the Definition of Clinically Inactive Disease in Juvenile Idiopathic Arthritis.

To investigate the effect of morning stiffness (MS) on parent disease perception in children with juvenile idiopathic arthritis (JIA) with clinically inactive disease (CID). We examined 652 visits in which patients fulfilled 2004 or 2011 Wallace criteria for CID. Parent-reported outcomes were compared among patients with no MS or with MS < or ≥ 15 min. Among 652 visits with CID by 2004 criteria, no MS was reported in 554 visits (85%), MS < 15 min in 53 (8%), and MS ≥ 15 min in 45 (7%). The frequency of altered physical function, health-related quality of life and well-being, pain, and disease activity visual analog scales was proportionally greater in patients without MS than those with longer MS. The frequency of parent subjective rating of disease state as remission was 87.7%, 58%, and 26.7% among patients with no MS, MS < 15 min, and MS ≥ 15 min, respectively. Our results suggest that a change in 2011 CID criteria to require absence of MS should be considered.