Active Joint Count Research Articles

Tocilizumab treatment in juvenile idiopathic arthritis patients: A single center experience.

Demir S, Sönmez HE, Arslanoğlu-Aydın E, Özen S, Bilginer Y. Tocilizumab treatment in juvenile idiopathic arthritis patients: A single center experience. Turk J Pediatr 2019; 61: 180-185. Tocilizumab is a monoclonal antibody against interleukin-6 that has recently emerged as an alternative treatment modality for juvenile idiopathic arthritis (JIA). In the present study, we aimed to discuss the clinical and laboratory findings and treatment response of JIA cases to tocilizumab therapy. This retrospective study included 20 JIA patients aged between 0-18 years who were followed up from 2014 to 2016 and received tocilizumab treatment in our clinic. Treatment response could be not evaluated in two patients since they developed anaphylactic reactions due to tocilizumab. Of the remaining 18 patients, seven of them (38.9%) had polyarticular JIA, and eleven (61.1%) had systemic JIA. Platelet counts, erythrocyte sedimentation rate and C-Reactive protein (CRP) levels, active joint counts, and Juvenile Arthritis Disease Activity Score 71 (JADAS71) were significantly decreased at the third month in both polyarticular and systemic JIA, while there were not any significant differences between the third and sixth months. All of the patients with polyarticular JIA had low disease activity at six months. Eight patients with systemic JIA had an inactive disease at six months, whereas the remaining three patients had high levels of CRP without presence of any clinical symptoms. Steroid treatment was terminated at the sixth month in all patients except for three patients who continued to receive 0.05-0.25 mg/kg steroid treatment. Two patients developed thrombocytopenia, one patient developed macrophage activation syndrome, and one patient had elevated transaminases due to tocilizumab treatment. Previous studies have shown that tocilizumab treatment is well-tolerated, effective, and safe for use in JIA patients. In the present study, we also demonstrated the efficacy of tocilizumab treatment in JIA patients from our clinic.

Late onset psoriatic arthritis in a longitudinal cohort: Disease presentation, activity over time and prognosis

AimsTo evaluate disease activity of late onset psoriatic arthritis (LoPsA) patients at presentation, during follow-up, and after 5years of follow-up, compared to young onset PsA patients (YoPsA). MethodsThe study included patients with PsA followed prospectively within 2years from diagnosis. Patients were divided into two groups: (1) LoPsA – defined as disease onset ≥ 50 years, (2) YoPsA – defined as disease onset < 50 years. Descriptive statistics are provided and multivariable logistic regression models were developed to compare these groups. ResultsFive hundred and sixty-six patients were included at presentation. Regression analysis showed that the LoPsA group at presentation was characterized by: less males (OR 0.4, p = 0.001), less HLA-C*06 (OR 0.3, p = 0.005), longer psoriasis duration (OR 1.04, p = 0.0005), higher BMI (OR 1.1, p = 0.005) and higher modified Steinbrocker score (mSS) (OR 1.1, p = 0.005).Regression analysis adjusted for gender, BMI, psoriasis duration, HLA and treatments after 5years of follow-up revealed a trend toward higher adjusted mean active joint count (OR 7.98, p = 0.052) and higher mean mSS score (OR 13.39, p = 0.007) in the LoSpA group compared to the YoPsA group. During 5years of follow-up, the YoPsA patients were treated with more NSAIDs (96% vs. 88%, p = 0.04), while there were no significant differences in the DMARDs and biologic drugs. ConclusionThe LoPsA patients at presentation are characterized by female predominance, higher BMI, more damage and less HLA-C*06. After 5years of follow-up the LoPsA patients have worse prognosis manifested by a trend toward higher disease activity burden and significantly more damage.

Prevalence and course of lower limb disease activity and walking disability over the first 5 years of juvenile idiopathic arthritis: results from the childhood arthritis prospective study.

ObjectiveThe aim was to investigate the time course of lower limb disease activity and walking disability in children with JIA over a 5-year course.MethodsThe Childhood Arthritis Prospective Study is a longitudinal study of children with a new JIA diagnosis. Childhood Arthritis Prospective Study data include demographics and core outcome variables at baseline, 6 months and yearly thereafter. Prevalence and transition rates from baseline to 5 years were obtained for active and limited joint counts at the hip, knee, ankle and foot joints; and walking disability, measured using the Childhood Health Assessment Questionnaire walking subscale. Missing data were accounted for using multiple imputation.ResultsA total of 1041 children (64% female), with a median age of 7.7 years at first visit, were included. Baseline knee and ankle synovitis prevalence was 71 and 34%, respectively, decreasing to 8–20 and 6–12%, respectively, after 1 year. Baseline hip and foot synovitis prevalence was <11%, decreasing to <5% after 6 months. At least mild walking disability was present in 52% at baseline, stabilizing at 25–30% after 1 year.ConclusionLower limb synovitis and walking disability are relatively common around the time of initial presentation in children and young people with JIA. Mild to moderate walking disability persisted in ∼25% of patients for the duration of the study, despite a significant reduction in the frequency of lower limb synovitis. This suggests that there is an unmet need for non-medical strategies designed to prevent and/or resolve persistent walking disability in JIA.

Depressive symptoms, pain and disability for adolescent patients with juvenile idiopathic arthritis: results from the Childhood Arthritis Prospective Study.

ObjectivesTo determine if depressive symptoms assessed near diagnosis associate with future measures of pain, disability and disease for adolescent patients diagnosed with JIA.MethodsData were analysed from JIA patients aged 11–16 years recruited to the Childhood Arthritis Prospective Study, a UK-based inception cohort of childhood-onset arthritis. Depressive symptoms (using the Mood and Feelings Questionnaire; MFQ), active and limited joint count, disability score (Childhood Health Assessment Questionnaire), pain visual analogue scale and patient’s general evaluation visual analogue scale were collected. Associations between baseline measures (first visit to paediatric rheumatologist) were analysed using multiple linear regression. Linear mixed-effect models for change in the clinical measures of disease over 48 months were estimated including MFQ as an explanatory variable.ResultsData from 102 patients were analysed. At baseline, median (IQR) age was 13.2 years (11.9–14.2 years) and 14.7% scored over the MFQ cut-off for major depressive disorder. At baseline, depressive symptoms significantly associated with all clinical measures of disease (P ⩽ 0.01). High baseline depressive symptoms scores predicted worse pain (P ⩽ 0.005) and disability (P ⩽ 0.001) 12 months later but not active and limited joint counts.ConclusionsAdolescent patients with JIA and depressive symptoms had more active joints, pain and disability at the time of their first specialist appointment. The associations between baseline depression and both pain and disability continued for at least one year, however, this was not the case for active joint count.

S100A12 and S100A8/9 proteins are biomarkers of articular disease activity in Blau syndrome.

To identify biomarkers of articular and ocular disease activity in patients with Blau syndrome (BS). Multiplex plasma protein arrays were performed in five BS patients and eight normal healthy volunteers (NHVs). Plasma S100A12 and S100A8/9 were subsequently measured by ELISA at baseline and 1-year follow-up in all patients from a prospective multicentre cohort study. CRP was measured using Meso Scale Discovery immunoassay. Active joint counts, standardization uveitis nomenclature for anterior uveitis cells and vitreous haze by Nussenblatt scale were the clinical parameters. Multiplex Luminex arrays identified S100A12 as the most significantly elevated protein in five selected BS vs eight NHVs and this was confirmed by ELISA on additional samples from the same five BS patients. In the patient cohort, S100A12 (n = 39) and S100A8/9 (n = 33) were significantly higher compared with NHVs (n = 44 for S100A12, n = 40 for S100A8/9) (P = 0.0000004 and P = 0.0003, respectively). Positive correlations between active joint counts and S100 levels were significant for S100A12 (P = 0.0008) and S100A8/9 (P = 0.015). CRP levels did not correlate with active joint count. Subgroup analysis showed significant association of S100 proteins with active arthritis (S100A12 P = 0.01, S100A8/9 P = 0.008). Active uveitis was not associated with increased S100 levels. S100 proteins are biomarkers of articular disease activity in BS and potential outcome measures in future clinical trials. As secreted neutrophil and macrophage products, S100 proteins may reflect the burden of granulomatous tissue in BS.

The correlation between the Childhood Health Assessment Questionnaire and disease activity in juvenile idiopathic arthritis.

The Childhood Health Assessment Questionnaire (CHAQ) has been adapted from the Stanford Health Assessment Questionnaire for assessing functional ability in children. The present study aimed to determine the correlation between CHAQ and disease activity in juvenile idiopathic arthritis (JIA) during active and inactive disease. JIA patients in the Pediatric Department, Ramathibodi Hospital, between January 2011 and December 2013, were included in the study. The CHAQ disability index (DI) and disease activity variables, including active and limited joint count, erythrocyte sedimentation rate, patient's global assessment (PtGA), physician's global assessment (PGA) and 27-joint Juvenile Arthritis Disease Activity Score (JADAS27), were collected from medical records for each patient over six visits. At each visit, each patient was classified as having either active or inactive disease. The correlations between CHAQ-DI and disease activity variables were analysed using Spearman's correlation. The classification of 139 JIA patients consisted of enthesitis-related arthritis (30.9%), systemic JIA (28.1%), oligoarthritis (16.5%), rheumatoid factor (RF)-negative polyarthritis (15.1%), RF-positive polyarthritis (6.5%) and undifferentiated arthritis (2.9%). Out of 812 patient visits, 606 were in active disease and 206 were in inactive disease. RF-negative polyarthritis had the highest CHAQ-DI (0.39 ± 0.66), while oligoarthritis had the lowest (0.20 ± 0.32). There was a good correlation between CHAQ-DI and JADAS27, PGA and PtGA in all JIA subtypes (p < 0.05) during active disease, but a poor correlation between CHAQ-DI and disease activity variables during inactive disease. CHAQ-DI had a good correlation with disease activity during active disease but a poor correlation during inactive disease. Therefore, CHAQ is only useful for assessing functional ability during active disease.

Characteristics and Course of Enthesitis in a Juvenile Idiopathic Arthritis Inception Cohort.

To describe the prevalence, associated characteristics, and course of enthesitis in a juvenile idiopathic arthritis (JIA) inception cohort. Canadian children newly diagnosed with JIA between 2005 and 2010 were categorized using International League of Associations for Rheumatology criteria at the 6-month visit and followed in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) cohort for up to 5 years. The presence of entheseal tenderness on examination at 33 sites shown on a homunculus was recorded at 0, 6, 12, 18, 24, 36, 48, and 60 months after enrollment. Enthesitis was defined as entheseal tenderness at more than 1 site or on more than 1 occasion. Analyses consisted of descriptive statistics and linear mixed models for longitudinal data. Of 1,406 patients, 219 (16%) had enthesitis and, of those with enthesitis, 141 (64%) were classified as having enthesitis-related arthritis (ERA). Children with enthesitis were more often older (10.7 versus 7.5 years), male (57% versus 31%), and with polyarthritis (57% versus 41%) and sacroiliac involvement (30% versus 4%). Entheseal tenderness was most frequent at the calcaneal plantar fascial insertion (39%), Achilles tendon insertion (31%), and tibial tuberosity (30%). The mean number of tender entheseal sites decreased in parallel with active joint counts. There was no difference in active joint counts over time in children with or without enthesitis (P = 0.73). Enthesitis was observed in 16% of patients with JIA, but only two thirds were categorized as having ERA. Contrary to expectations, most children with enthesitis had polyarticular involvement. The course of enthesitis paralleled the course of active joint counts.

Practice and consensus-based strategies in diagnosing and managing systemic juvenile idiopathic arthritis in Germany

BackgroundSystemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory disease associated with chronic arthritis. Early diagnosis and effective therapy of SJIA is desirable, so that complications are avoided. The PRO-KIND initiative of the German Society for Pediatric Rheumatology (GKJR) aims to define consensus-based strategies to harmonize diagnostic and therapeutic approaches in Germany.MethodsWe analyzed data on patients diagnosed with SJIA from 3 national registries in Germany. Subsequently, via online surveys and teleconferences among pediatric rheumatologists with a special expertise in the treatment of SJIA, we identified current diagnostic and treatment approaches in Germany. Those were harmonized via the formulation of statements and, supported by findings from a literature search. Finally, an in-person consensus conference using nominal group technique was held to further modify and consent the statements.ResultsUp to 50% of patients diagnosed with SJIA in Germany do not fulfill the International League of Associations for Rheumatology (ILAR) classification criteria, mostly due to the absence of chronic arthritis. Our findings suggest that chronic arthritis is not obligatory for the diagnosis and treatment of SJIA, allowing a diagnosis of probable SJIA. Malignant, infectious and hereditary autoinflammatory diseases should be considered before rendering a diagnosis of probable SJIA. There is substantial variability in the initial treatment of SJIA. Based on registry data, most patients initially receive systemic glucocorticoids, however, increasingly substituted or accompanied by biological agents, i.e. interleukin (IL)-1 and IL-6 blockade (up to 27.2% of patients). We identified preferred initial therapies for probable and definitive SJIA, including step-up patterns and treatment targets for the short-term (resolution of fever, decrease in C-reactive protein by 50% within 7 days), the mid-term (improvement in physician global and active joint count by at least 50% or a JADAS-10 score of maximally 5.4 within 4 weeks) and the long-term (glucocorticoid-free clinically inactive disease within 6 to 12 months), and an explicit treat-to-target strategy.ConclusionsWe developed consensus-based strategies regarding the diagnosis and treatment of probable or definitive SJIA in Germany.

Micro-structural bone changes in early rheumatoid arthritis persist over 1-year\xa0despite use of disease modifying anti-rheumatic drug therapy

BackgroundWe used High Resolution – peripheral Quantitative CT (HR-pQCT) imaging to examine peri-articular bone quality in early rheumatoid arthritis (RA) and explore whether bone quality improved over 12-months in individuals receiving care consistent with practice guidelines.MethodsA 1-year longitudinal cohort study (Baseline and 12-months) evaluating individuals with early RA compared to age/sex-matched peers. Personal demographic and health and lifestyle information were collected for all. Whereas, active joint count (AJC28), functional limitation, and RA medications were also collected for RA participants. HR-pQCT imaging analyses quantified bone density and microstructure in the Metacarpal Head (MH) and Ultra-Ultra-Distal (UUD) radius at baseline and 12-months. Analyses included a General Linear Modelling repeated measures analyses examined main effects for disease, time, and interaction on bone quality.ResultsParticipants (n = 60, 30 RA/30 NRA); 80% female, mean age 53 (varying from 21 to 74 years). At baseline, RA participants were on average 7.7 months since diagnosis, presenting with few active joints (AJC28: 30% none, remaining 70% Median 4 active joints) and minimal self-reported functional limitation (mHAQ-DI0–3: 0.56). At baseline, 29 of 30 RA participants had received one or more non-biologic disease-modifying anti-rheumatic drugs (DMARD);13 in combination with glucocorticoid and 1 in combination with a biologic medication. One participant only received glucocorticoid medication. Four RA participants withdrew leaving 26 pairs (n = 52) at 12-months; 23 pairs (n = 46) with UUD and 22 pairs (n = 44) with MH baseline and 12-month images to compare. Notable RA/NRA differences (p < 0.05) in bone quality at all three sites included lower trabecular bone density and volume, more rod-like trabeculae, and larger and more variable spaces between trabeculae; fewer trabeculae at the UUD and MH2 sites; and lower cortical bone density and volume in the MH sites. Rate of change over 12-months did not differ between RA/NRA participants which meant there was also no improvement over the year in RA bone quality.ConclusionsEarly changes in peri-articular bone density and microstructure seen in RA are consistent with changes more commonly seen in aging bone and are slow or resistant to recover despite well controlled inflammatory joint symptoms with early DMARD therapy.

Trajectories of pain severity in juvenile idiopathic arthritis: results from the Research in Arthritis in Canadian Children Emphasizing Outcomes cohort.

We studied children enrolled within 90 days of juvenile idiopathic arthritis diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) prospective inception cohort to identify longitudinal trajectories of pain severity and features that may predict pain trajectory at diagnosis. A total of 1062 participants were followed a median of 24.3 months (interquartile range = 16.0-37.1 months). Latent trajectory analysis of pain severity, measured in a 100-mm visual analogue scale, identified 5 distinct trajectories: (1) mild-decreasing pain (56.2% of the cohort); (2) moderate-decreasing pain (28.6%); (3) chronically moderate pain (7.4%); (4) minimal pain (4.0%); and (5) mild-increasing pain (3.7%). Mean disability and quality of life scores roughly paralleled the pain severity trajectories. At baseline, children with chronically moderate pain, compared to those with moderate-decreasing pain, were older (mean 10.0 vs 8.5 years, P = 0.01) and had higher active joint counts (mean 10.0 vs 7.2 joints, P = 0.06). Children with mild-increasing pain had lower joint counts than children with mild-decreasing pain (2.3 vs 5.2 joints, P < 0.001). Although most children with juvenile idiopathic arthritis in this cohort had mild or moderate initial levels of pain that decreased quickly, about 1 in 10 children had concerning pain trajectories (chronically moderate pain and mild-increasing pain). Systematic periodic assessment of pain severity in the months after diagnosis may help identify these concerning pain trajectories early and lay out appropriate pain management plans. Focused research into the factors leading to these concerning trajectories may help prevent them.

Power Color Doppler and Spectral Doppler Ultrasonography to Evaluate Response to Intra-articular Steroid Injection in Knee Joints in Juvenile Idiopathic Arthritis.

To evaluate the role of ultrasonographic indices (Color Fraction and Resistive Index) in assessing the effect of intra-articular steroid (IAS) injection on synovial inflammation in knee joints of Juvenile Idiopathic Arthritis (JIA) patients and to determine the correlation between these ultrasonographic indices and clinical and laboratory parameters in JIA patients after IAS. Twenty seven patients of JIA and equal number of age and sex matched healthy controls were enrolled. Thirty six knee joints were injected with IAS. Duration of morning stiffness, swelling score, tenderness score, range of motion, visual analogue scale for pain, Physician global assessment of disease activity, Patient/Parent assessment of general well being, Juvenile Arthritis Disease Activity Score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), synovial thickness, synovial effusion, Color fraction (CF) and Resistive index (RI) were measured at base line and at one and two months of follow-up. At baseline, a significant difference was found in ESR, CRP, CF and RI values between cases and controls. A significant decrease in various clinical, core set variables and ultrasonographic parameters was observed at each follow-up. Synovial thickness, synovial effusion and CF decreased by 51.78%, 64.67% and 49.35% respectively and range of motion and RI increased by 166% and 31.94% respectively at second follow-up. Both CF and RI showed a significant correlation with active joint count. Both CF and RI had a high inter and intra-class correlation. Power Color Doppler and Spectral Doppler ultrasonographic indices (CF and RI) may have a role in assessment of the response to IAS injection of inflamed knee joints.

Multicenter inception cohort of enthesitis-related arthritis: variation in disease characteristics and treatment approaches

BackgroundEnthesitis-related arthritis (ERA) is a specific subtype of juvenile idiopathic arthritis (JIA) defined according to the International League of Associations for Rheumatology (ILAR) criteria. We aimed to characterize the clinical features and treatment regimens in an inception cohort of children with ERA.MethodsWe performed a retrospective, cross-sectional, multicenter cohort study including subjects diagnosed with ERA between 1989 and 2012. Patients all fulfilled the ILAR criteria for ERA within 3 months of initial presentation to the rheumatology clinic. Differences in the prevalence of clinical criteria across study sites and by human leukocyte antigen (HLA)-B27 status were assessed using the Wilcoxon rank-sum or chi-square test, as appropriate.ResultsTwo hundred thirty-four children met the inclusion criteria. Their median age at diagnosis was 11.6 years, and 59% were HLA-B27-positive. Sixty-nine percent had enthesitis and arthritis at the time of diagnosis. Seventy-eight percent had a pauciarticular onset. The prevalence of all ILAR criteria at diagnosis, except arthritis and acute anterior uveitis, differed significantly across sites (all p < 0.01). Medication use varied significantly across sites for children with peripheral arthritis (p < 0.001), but not for sacroiliitis or enthesitis only. Nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs were the most commonly prescribed treatments, with anti-TNF agents primarily being initiation for sacroiliitis. HLA-B27 positivity was associated with male sex, higher active joint count, sacroiliitis, and higher disease activity at disease onset.ConclusionsThe majority of children had a pauciarticular onset, and several statistically significant clinical differences based on HLA-B27 status were identified. The observed heterogeneity in clinical presentation across sites reflects either true differences in patient populations or differences in how the ILAR criteria are being applied.

The profile of polyunsaturated fatty acids in juvenile idiopathic arthritis and association with disease activity

We investigated the association between dietary intake of n-3 and n-6 polyunsaturated fatty acids (PUFAs), serum profiles, and immune and inflammatory markers in juvenile idiopathic arthritis (JIA) in relation to onset, activity, and duration. A total of 66 JIA patients and 42 controls were included. Serum PUFA levels were assessed by gas-liquid chromatography-mass spectrometry, a dietary intake by 7-day dietary record method, and IL-6, IL-10, and IL-17A levels using ELISA. Dietary PUFA intake did not differ between the JIA group and controls. Intakes of n-6 and n-3 PUFA and serum levels were not associated. Levels of total n-6 PUFA and linoleic acid (LA) were higher in inactive JIA than in active JIA. Patients with active and short-lasting disease (less than 3 months from diagnosis) had significantly lower levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) than the control. Serum α-linolenic acid (ALA) levels were significantly higher in poly-JIA than in oligo-JIA and in controls. We found significantly higher serum IL-10 levels in JIA than in controls. Serum n-6 and n-3 levels were significantly negatively correlated with active joint count, erythrocyte sedimentation rate, and C-reactive protein and positively with platelet count. Our study presents the low levels of AA and DHA in the active phase of short-lasting JIA, particularly poly-JIA, and the relationship between n-6 and n-3 PUFA and classic markers of inflammation. PUFAs may contribute to the pathogenesis of JIA and support a necessity to identify new targets suitable for successful interventional studies in JIA patients.

Inflammatory Markers and Disease Activity in Juvenile Idiopathic Arthritis.

To evaluate the post treatment changes in disease activity and inflammatory markers over time in longitudinal follow-up involving different subtypes of juvenile idiopathic arthritis (JIA) patients. This prospective longitudinal study, carried out over a period of 2 y, included JIA patients, both old and new, with high disease activity. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ferritin, CHAQ (Childhood Health Assessment Questionnaire) score and JADAS27 (Juvenile Arthritis Disease Activity score with 27 active joint counts) were estimated at the initial visit, 6 mo, 12 mo and 18 mo of follow-up. Out of 40 patients, 10 had persistent oligoarthritis, 11 had rheumatoid factor (RF) positive polyarthritis, 8 had RF negative polyarthritis and 11 had systemic JIA. Twenty-one of them were females. Serum ferritin was highly elevated in systemic JIA patients with a range of 750-7712ng/ml at the initial visit. All three inflammatory markers with disease activity score decreased significantly over 18-mo-period in all four subtypes. At any visit, all these parameters had largest value in systemic arthritis and least in oligoarthritis variety. At 18 mo, all oligoarthritis and polyarthritis cases had low or inactive disease while none of the systemic JIA patients achieved inactive disease. Elevated ESR and serum ferritin was found in all at 18 mo. CRP normalized in some with low or moderate disease activity. Inflammatory markers and disease activity decreased in all subtypes of JIA with treatment without biologics. Acute phase markers often remain elevated in inactive disease state. Similarly, normal level of an inflammatory marker does not necessarily indicate absence of active disease.

A comparison of three treatment strategies in recent onset non-systemic Juvenile Idiopathic Arthritis: initial 3-months results of the BeSt for Kids-study

BackgroundCombination therapy with prednisone or etanercept may induce earlier and/or more improvement in disease activity in Disease Modifying Anti Rheumatic Drug (DMARD) naïve non-systemic Juvenile Idiopathic Arthritis (JIA) patients. Here we present three months clinical outcome of initial treatments of the BeSt-for-Kids study.MethodsIncluded patients were randomized to either: 1. initial DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate (MTX)), 2. Initial MTX / prednisolone-bridging, 3. Initial combination MTX/etanercept. Percentage inactive disease, adjusted (a) ACR Pedi30, 50 and 70 and JADAS after 6 and 12 weeks of treatment (intention to treat analysis) and side effects are reported.Results94 patients (67% girls, 32 (arm 1), 32 (arm 2) and 30 (arm 3) with median (InterQuartileRange) age of 9.1 (4.7-12.9) years were included. 38% were ANA positive, 10 had oligo-articular disease, 68 polyarticular JIA and 16 psoriatic arthritis. Baseline median (IQR) ACRpedi-scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6.5 (2-14.8)mm/hr, active joint count 8 (5-12), limited joint count 3 (1-5), CHAQ score 0.88 (0.63-1.5). In arm 1, 17 started with MTX, 15 with SSZ.After 3 months, aACR Pedi 50 was reached by 10/32 (31%), 12/32(38%) and 16/30 (53%) (p = 0.19) and aACR Pedi 70 was reached by 8/32 (25%), 6/32(19%) and 14/30(47%) in arms 1-3 (p = 0.04). Toxicity was similar. Few serious adverse events were reported.ConclusionAfter 3 months of treatment in a randomized trial, patients with recent-onset JIA achieved significantly more clinical improvement (aACRPedi70) on initial combination therapy with MTX / etanercept than on initial MTX or SSZ monotherapy.Trial registrationNTR1574. Registered 3 December 2008.

Predicting Which Children with Juvenile Idiopathic Arthritis Will Have a Severe Disease Course: Results from the ReACCh-Out Cohort.

We studied an inception cohort of children with juvenile idiopathic arthritis (JIA) to (1) identify distinct disease courses based on changes over 5 years in 5 variables prioritized by patients, parents, and clinicians; and (2) estimate the probability of a severe disease course for each child at diagnosis. Assessments of quality of life, pain, medication requirements, patient-reported side effects, and active joint counts were scheduled at 0, 6, 12, 18, 24, 36, 48, and 60 months. Patients who attended at least 6 assessments were included. Multivariable cluster analysis, r2, and silhouette statistics were used to identify distinct disease courses. One hundred candidate prediction models were developed in random samples of 75% of the cohort; their reliability and accuracy were tested in the 25% not used in their development. Four distinct courses were identified in 609 subjects. They differed in prioritized variables, disability scores, and probabilities of attaining inactive disease and remission. We named them Mild (43.8% of children), Moderate (35.6%), Severe Controlled (9%), and Severe Persisting (11.5%). A logistic regression model using JIA category, active joint count, and pattern of joint involvement at enrollment best predicted a severe disease course (Controlled + Persisting, c-index = 0.87); 91% of children in the highest decile of risk actually experienced a severe disease course, compared to 5% of those in the lowest decile. Children in this JIA cohort followed 1 of 4 disease courses and the probability of a severe disease course could be estimated with information available at diagnosis.

Physical activity levels of children with juvenile idiopathic arthritis

Children with juvenile idiopathic arthritis (JIA) have lower levels of moderate to vigorous physical activity (MVPA) and spend longer in sedentary activities than their peers. A study to assess the physical activity levels at a tertiary Irish centre was undertaken to compare children with JIA in Ireland against the international experience. Children with JIA completed a nine-item validated questionnaire, the Physical Activity Questionnaire for Children (PAQ-C). Pain, medication use and disease subtype were recorded. PAQ-C scores were compared against UK threshold values. Estimated %MVPA and time (min/day) were calculated using a published formula. Fifty-three children with JIA (33 female, 20 male, mean 11.4 years) completed the PAQ-C. Mean PAQ-C level was 2.7 for males and 2.4 for females. One-third of children met the threshold levels for being sufficiently active (normative values 2.9 males, 2.7 females). Using estimated %MVPA, one-third did not achieve 30 min of MVPA. There was no significant difference in PAQ-C levels between children with active disease (active joint count >1, self-reported visual analogue scale pain >1 and elevated erythrocyte sedimentation rate/C-reactive protein) and those without active markers. Using both the PAQ-C and estimated MVPA, only one-third of children with JIA met the recommended 60 min of daily MVPA. This needs to be validated against objective measures, e.g. accelerometers.

Using epidemiological registry data to provide background rates as context for adverse events in a rheumatoid arthritis drug development program: a coordinated approach.

Observational studies can provide context for adverse events observed in clinical trials, especially for infrequent events or long-term risks. We developed methods to improve safety contextualization for a rheumatoid arthritis drug development program through coordinated analyses of multiple registries. We identified and characterized differences and similarities across five registries (Swedish Rheumatology Quality of Care Register, Consortium of Rheumatology Researchers of North America [CORRONA], Norfolk Arthritis Register, Institute of Rheumatology Rheumatoid Arthritis, and the new CORRONA International), harmonized outcome definitions, and investigated whether restricted subcohorts improved comparability with trial populations. To address confounding, we identified risk predictors for outcomes of interest (mortality, cardiovascular disease, infection, and malignancy). We used patient-level analyses at each registry and central analysis of standardized group-level data. Despite data differences, the coordinated approach enabled consistent variable definitions for key baseline characteristics and outcomes. Selection of restricted subcohorts (e.g., using active joint count criteria) improved baseline comparability with trial patients for some rheumatoid arthritis disease activity measures, but less for other characteristics (e.g., age and comorbidity); however, such selection decreased sample size considerably. For most outcomes, age was the most important risk predictor, emphasizing the importance of age/sex standardization to address confounding. The prospective approach enabled use of recent relevant data; the distributed analysis safeguarded confidentiality of registry data. Compared with reliance on published data alone, a forward-looking coordinated approach across multiple observational data sources can improve comparability and consistency and better support sensitivity analyses and data interpretation, in contextualizing safety data from clinical trials. This approach may have utility to support safety assessments across diverse diseases and drug development programs and satisfy future regulatory requirements.

Juvenile spondyloarthritis.

This article provides a comprehensive update of the pathogenesis, diagnostic imaging, treatments, and disease activity measurements of juvenile spondyloarthritis (JSpA). Genetic and microbiome studies have provided new information regarding possible pathogenesis of JSpA. Recent work suggests that children with JSpA have decreased thresholds for pain in comparison to healthy children. In addition, pain on physical examination and abnormalities on ultrasound of the entheses are not well correlated. Treatment guidelines for juvenile arthritis, including JSpA, were published by the American College of Rheumatology and are based on active joint count and presence of sacroiliitis. Recent studies have established the efficacy of tumor necrosis factor inhibitors in the symptomatic treatment of axial disease, although their efficacy for halting progression of structural damage is less clear. Newly developed disease activity measures for JSpA include the Juvenile Arthritis Disease Activity Score and the JSpA disease activity index. In comparison to other categories of juvenile arthritis, children with JSpA are less likely to attain and sustain inactive disease. Further microbiome and genetic research may help elucidate JSpA pathogenesis. More randomized therapeutic trials are needed and the advent of new composite disease activity measurement tools will hopefully allow the design of these greatly needed trials.

The risk and nature of flares in juvenile idiopathic arthritis: results from the ReACCh-Out cohort

ObjectiveTo describe probabilities and characteristics of disease flares in children with juvenile idiopathic arthritis (JIA) and to identify clinical features associated with an increased risk of flare.MethodsWe studied children in...