Juvenile idiopathic arthritis patients with positive family history of autoimmune thyroid disease might benefit from serological screening: analysis of the international Pharmachild registry.

BACKGROUND: Little is known about the association between juvenile idiopathic arthritis (JIA) and autoimmune thyroid disease (AITD) and therefore there are no indications for AITD screening in this population, which is possible using standard blood tests. The objective of this study is to determine the prevalence and predictors of symptomatic AITD in JIA patients from the international Pharmachild registry. METHODS: Occurrence of AITD was determined from adverse event forms and comorbidity reports. Associated factors and independent predictors for AITD were determined using univariable and multivariable logistic regression analyses. RESULTS: The prevalence of AITD after a median observation period of 5.5 years was 1.1% (96/8965 patients). Patients who developed AITD were more often female (83.3% vs. 68.0%), RF positive (10.0% vs. 4.3%) and ANA positive (55.7% vs. 41.5%) than patients who did not. AITD patients were furthermore older at JIA onset (median 7.8 years vs. 5.3 years) and had more often polyarthritis (40.6% vs. 30.4%) and a family history of AITD (27.5% vs. 4.8%) compared to non-AITD patients. A family history of AITD (OR = 6.8, 95% CI: 4.1 - 11.1), female sex (OR = 2.2, 95% CI: 1.3 - 4.3), ANA positivity (OR = 2.0, 95% CI: 1.3 - 3.2) and older age at JIA onset (OR = 1.1, 95% CI: 1.1 - 1.2) were independent predictors of AITD on multivariable analysis. Based on our data, 16 female ANA positive JIA patients with a family history of AITD would have to be screened during ±5.5 years using standard blood tests to detect one case of AITD. CONCLUSIONS: This is the first study to report independent predictor variables for symptomatic AITD in JIA. Female ANA positive JIA patients with positive family history are at increased risk of developing AITD and thus might benefit from yearly serological screening.

Prevalence of familial autoimmune diseases in juvenile idiopathic arthritis: results from the international Pharmachild registry.

BACKGROUND: Little is known about the disposition to autoimmune diseases (ADs) among children diagnosed with JIA. In this study, we provide a comprehensive overview of the prevalence of and factors associated with ADs in parents of children with juvenile idiopathic arthritis (JIA). METHODS: Prevalence rates of ADs and 95% Poisson confidence intervals were calculated for parents of JIA patients from the international Pharmachild registry and compared with general population prevalence rates as reported in the literature. Demographic, clinical and laboratory features were compared between JIA patients with and without a family history of AD using χ2 and Mann-Whitney U tests. RESULTS: Eight thousand six hundred seventy three patients were included and the most common familial ADs were psoriasis, autoimmune thyroid disease, rheumatoid arthritis and ankylosing spondylitis. The prevalence of several ADs was higher in parents of the included JIA patients than in the general population. Clinical Juvenile Arthritis Disease Activity Scores at study entry and last follow-up were not significantly different between patients with (n = 1231) and without a family history of AD (n = 7442). Factors associated with familial AD were older age at JIA onset (P < 0.01), Scandinavian residence (P < 0.01), enthesitis-related arthritis, psoriatic arthritis and undifferentiated arthritis (P < 0.01), ANA positivity (P = 0.03) and HLA-B27 positivity (P < 0.01). CONCLUSIONS: Familial AD proves to be a risk factor for JIA development and certain diseases should therefore not be overlooked during family health history at the diagnosis stage. A family history of AD is associated with the JIA category but does not influence the severity or disease course.

Real-world comparison of the effects of etanercept and adalimumab on well-being in non-systemic juvenile idiopathic arthritis: a propensity score matched cohort study.

BACKGROUND: Etanercept (ETN) and adalimumab (ADA) are considered equally effective biologicals in the treatment of arthritis in juvenile idiopathic arthritis (JIA) but no studies have compared their impact on patient-reported well-being. The objective of this study was to determine whether ETN and ADA have a differential effect on patient-reported well-being in non-systemic JIA using real-world data. METHODS: Biological-naive patients without a history of uveitis were selected from the international Pharmachild registry. Patients starting ETN were matched to patients starting ADA based on propensity score and outcomes were collected at time of therapy initiation and 3-12 months afterwards. Primary outcome at follow-up was the improvement in Juvenile Arthritis Multidimensional Assessment Report (JAMAR) visual analogue scale (VAS) well-being score from baseline. Secondary outcomes at follow-up were decrease in active joint count, adverse events and uveitis events. Outcomes were analyzed using linear and logistic mixed effects models. RESULTS: Out of 158 eligible patients, 45 ETN starters and 45 ADA starters could be propensity score matched resulting in similar VAS well-being scores at baseline. At follow-up, the median improvement in VAS well-being was 2 (interquartile range (IQR): 0.0 - 4.0) and scores were significantly better (P = 0.01) for ETN starters (median 0.0, IQR: 0.0 - 1.0) compared to ADA starters (median 1.0, IQR: 0.0 - 3.5). The estimated mean difference in VAS well-being improvement from baseline for ETN versus ADA was 0.89 (95% CI: -0.01 - 1.78; P = 0.06). The estimated mean difference in active joint count decrease was -0.36 (95% CI: -1.02 - 0.30; P = 0.28) and odds ratio for adverse events was 0.48 (95% CI: 0.16 -1.44; P = 0.19). One uveitis event was observed in the ETN group. CONCLUSIONS: Both ETN and ADA improve well-being in non-systemic JIA. Our data might indicate a trend towards a slightly stronger effect for ETN, but larger studies are needed to confirm this given the lack of statistical significance.

Emerging therapies for juvenile arthritis: agents in early clinical trials.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic condition in childhood. The management of JIA has been revolutionized thanks to the development of new powerful drugs and the possibility to conduct controlled clinical trials with support from legislative initiatives and availability of international collaborative networks. Trials are still needed in children because we now have new drugs related to specific JIA category. AREAS COVERED: The review is centered on the latest achievements in the field, focusing on new investigational drugs which are currently or have been recently tested for JIA treatment, encompassing agents in early phase of clinical development. EXPERT OPINION: Despite the tremendous improvement witnessed in the field of JIA treatment in the past 20 years, there are still many unmet needs to be prioritized. Studies on disease pathogenesis will hopefully help in the identification of new treatment targets for individual JIA categories, that could possibly favor a stricter disease control and contribute to solve the issue of refractory JIA. Novel strategies aimed at the prevention of the risk of long-term joint damage are also desirable, as well as the discovery of predictive biomarkers for treatment efficacy and safety in the individual patient.

Drivers of non-zero physician global scores during periods of inactive disease in juvenile idiopathic arthritis.

OBJECTIVE: To investigate the frequency in which the physician provides a global assessment of disease activity (PhGA) >0 and an active joint count (AJC)=0 in children with juvenile idiopathic arthritis (JIA) and search for determinants of divergence between the two measures. METHODS: Data were extracted from a multinational cross-sectional dataset of 9966 patients who had JIA by International League of Associations for Rheumatology criteria, were recruited between 2011 and 2016, and had both PhGA and AJC recorded by the caring paediatric rheumatologist at the study visit. Determinants of discordance between PhGA>0 and AJC=0 were searched for by multivariable logistic regression and dominance analyses. RESULTS: The PhGA was scored >0 in 1647 (32.3%) of 5103 patients who had an AJC of 0. Independent associations with discordant assessment were identified for tender or restricted joint count >0, history of enthesitis, presence of active uveitis or systemic features, enthesitis-related or systemic arthritis, increased acute phase reactants, pain visual analogue scale (VAS)>0, and impaired physical or psychosocial well-being. In dominance analysis, tender joint count accounted for 35.43% of PhGA variance, followed by pain VAS>0 (17.72%), restricted joint count >0 (16.14%) and physical health score >0 (11.42%). CONCLUSION: We found that many paediatric rheumatologists did not mark a score of 0 for patients who they found not to have active joints. The presence of pain in joints not meeting the definition of active joint used in JIA was the main determinant of this phenomenon.

Anakinra in Patients With Systemic Juvenile Idiopathic Arthritis: Long-term Safety From the Pharmachild Registry.

OBJECTIVE: To evaluate the long-term safety profile of anakinra in patients with systemic juvenile idiopathic arthritis (sJIA). METHODS: Data from patients with sJIA enrolled in the Pharmachild registry (ClinicalTrials.gov: NCT03932344) prior to September 30, 2018, and treated with anakinra were analyzed. The study endpoints were the occurrence of non-serious adverse events (SAEs) of at least moderate severity and SAEs, including macrophage activation syndrome (MAS), and the duration of anakinra treatment with reasons for discontinuation. All endpoints were analyzed overall by 6-month time windows, and in different treatment sets represented by those patients treated continuously with anakinra for at least 12, 18, and 24 months (set-12, -18, and -24, respectively). RESULTS: Three hundred six patients were enrolled. Of these patients, 46%, 34%, and 28% had been treated for at least 12, 18, and 24 months, respectively. Two hundred and one AEs, mostly represented by infections, were reported for 509.3 patient-years (PY) with an overall incidence rate (IR) of 39.5 per 100 PY. Among 56 SAEs (IR 11.0/100 PY), 23.2% were infections and 19.6% MAS episodes. The IR of AEs was higher during the first 6 months of anakinra treatment, followed by decreasing IRs in the long-term treatment sets. Treatment discontinuation occurred in 76% of patients, most frequently in the first 6 months, because of inefficacy (43%), remission (31%), or AEs/intolerance (15%). No deaths or malignancies occurred during anakinra treatment. CONCLUSION: The results of the present study confirm the long-term safety profile of anakinra in patients with sJIA and demonstrate an overall decreasing incidence of AEs over time. [ClinicalTrials.gov: NCT01399281 and NCT03932344].

Disparities in the prevalence of clinical features between systemic juvenile idiopathic arthritis and adult-onset Still's disease.

OBJECTIVE: To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still's disease (AOSD). METHODS: The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered. RESULTS: A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA. CONCLUSION: We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.

Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use.

OBJECTIVE: To describe risk factors for IBD development in a cohort of children with JIA. METHODS: JIA patients who developed IBD were identified from the international Pharmachild register. Characteristics were compared between IBD and non-IBD patients and predictors of IBD were determined using multivariable logistic regression analysis. Incidence rates of IBD events on different DMARDs were calculated, and differences between therapies were expressed as relative risks (RR). RESULTS: Out of 8942 patients, 48 (0.54% ) developed IBD. These were more often male (47.9% vs 32.0%) and HLA-B27 positive (38.2% vs 21.0%) and older at JIA onset (median 8.94 vs 5.33 years) than patients without IBD development. They also had more often a family history of autoimmune disease (42.6% vs 24.4%) and enthesitis-related arthritis (39.6% vs 10.8%). The strongest predictors of IBD on multivariable analysis were enthesitis-related arthritis [odds ratio (OR): 3.68, 95% CI: 1.41, 9.40] and a family history of autoimmune disease (OR: 2.27, 95% CI: 1.12, 4.54). Compared with methotrexate monotherapy, the incidence of IBD on etanercept monotherapy (RR: 7.69, 95% CI: 1.99, 29.74), etanercept with methotrexate (RR: 5.70, 95% CI: 1.42, 22.77) and infliximab (RR: 7.61, 95% CI: 1.27, 45.57) therapy was significantly higher. Incidence on adalimumab was not significantly different (RR: 1.45, 95% CI: 0.15, 13.89). CONCLUSION: IBD in JIA was associated with enthesitis-related arthritis and a family history of autoimmune disease. An increased IBD incidence was observed for etanercept therapy regardless of concomitant methotrexate use.

Burden of comorbid conditions in children and young people with juvenile idiopathic arthritis: a collaborative analysis of 3 JIA registries.

OBJECTIVES: Burden of comorbidities are largely unknown in JIA. From 2000, national and international patient registries were established to monitor biologic treatment, disease activity and adverse events in patients with JIA. The aim of this analysis was to investigate in parallel, for the first time, three of the largest JIA registries in Europe/internationally-UK JIA Biologic Registers (BCRD/BSPAR-ETN), German biologic registers (BiKeR/JuMBO), multinational Pharmachild-to quantify the occurrence of selected comorbidities in patients with JIA. METHODS: Information on which data the registers collect were compared. Patient characteristics and levels of comorbidity were presented, focussing on four key conditions: uveitis, MAS, varicella, and history of tuberculosis. Incidence rates of these on MTX/biologic therapy were determined. RESULTS: 8066 patients were registered into the three JIA registers with similar history of the four comorbidities across the studies; however, varicella vaccination coverage was higher in Germany (56%) vs UK/Pharmachild (16%/13%). At final follow-up, prevalence of varicella infection was lower in Germany (15%) vs UK/Pharmachild (37%/50%). Prevalence of TB (0.1-1.8%) and uveitis (15-19%) was similar across all registers. The proportion of systemic-JIA patients who ever had MAS was lower in Germany (6%) vs UK (15%) and Pharmachild (17%). CONCLUSION: This analysis is the first and largest to investigate the occurrence of four important comorbidities in three JIA registries in Europe and the role of anti-rheumatic drugs. Combined, these three registries represent one of the biggest collection of cases of JIA worldwide and offer a unique setting for future JIA outcome studies.

A prediction rule for polyarticular extension in oligoarticular-onset juvenile idiopathic arthritis.

OBJECTIVES: To search for predictors of polyarticular extension in children with oligoarticular-onset juvenile idiopathic arthritis (JIA) and to develop a prediction model for an extended course. METHODS: The clinical charts of consecutive patients with oligoarticular-onset JIA and ≥2 years of disease duration were reviewed. Predictor variables included demographic data, number and type of affected joints, presence of iridocyclitis, laboratory tests including antinuclear antibodies, and therapeutic interventions in the first 6 months. Joint examinations were evaluated to establish whether after the first 6 months of disease patients had persistent or extended course (i.e. involvement of 4 or less, or 5 or more joints). Statistics included univariable and multivariable analyses. Regression coefficients (ß) of variables that entered the best-fitting logistic regression model were converted and summed to obtain a "prediction score" for an extended course. RESULTS: A total of 480 patients with a median disease duration of 7.4 years were included. 61.2% had persistent oligoarthritis, whereas 38.8% experienced polyarticular extension. On multivariable analysis, independent correlations with extended course were identified for the presence of ≥2 involved joints and a CRP >0.8 mg/dl in the first 6 months. The prediction score ranged from 0 to 6 and its cut-off that discriminated best between patients who had or did not have polyarticular extension was >1. Sensitivity and specificity were 59.6 and 79.8, respectively. CONCLUSIONS: The number of affected joints and the CRP level in the first 6 months were the strongest predictors of polyarticular extension in our children with oligoarticular-onset JIA.

Outcome Scores in Pediatric Rheumatology.

PURPOSE OF REVIEW: Providing a summary of the latest research on outcome measures in juvenile idiopathic arthritis, childhood -onset systemic lupus erythematosus, and juvenile dermatomyositis. RECENT FINDINGS: A rational management of patients with pediatric rheumatic diseases requires the regular assessment of the level of disease activity and damage, as well as the evaluation of therapeutic response through validated and standardized outcome measures. Ideally, such tools should be simple, feasible, and easily applicable in routine care. Recently, there has been a great deal of effort to refine existing tools and devise novel outcome measures, aiming to address the various aspects of disease impact and to improve the reliability of research studies and clinical trials. The newest outcome tools in pediatric rheumatology have markedly enlarged the spectrum of health domains assessable in a standardized way, thus increasing the reliability of evaluation of clinical response and fostering future clinical trials.

Determinants of Discordance Between Criteria for Inactive Disease and Low Disease Activity in Juvenile Idiopathic Arthritis.

OBJECTIVE: To assess concordance among criteria for inactive disease (ID) and low disease activity (LDA) in juvenile idiopathic arthritis (JIA) and to seek factors driving discordance. METHODS: The frequency of fulfillment of existing criteria was evaluated in information on 10,186 patients extracted from 3 cross-sectional data sets. Patients were divided up according to the functional phenotypes of oligoarthritis and polyarthritis. Concordance between criteria was examined using weighted Venn diagrams. The role of each individual component in explaining discordance between criteria was assessed by calculating the absolute number and percentage of instances in which the component was responsible for discrepancy between definitions. RESULTS: Criteria for ID were met by 28.6-41.1% of patients with oligoarthritis and by 24.0-33.4% of patients with polyarthritis. Criteria for LDA were met by 44.8-62.4% of patients with oligoarthritis and by 44.6-50.4% of patients with polyarthritis. There was a 57.9-62.3% overlap between criteria for ID and a 67.9-85% overlap between criteria for LDA. Parent and physician global assessments and acute-phase reactants were responsible for the majority of instances of discordance among criteria for ID (8.7-15.5%, 10.0-12.3%, and 10.8-17.3%, respectively). CONCLUSION: We found fair concordance between criteria for ID and LDA in JIA, with the main drivers of discordance for ID being physician and parent global assessments and acute-phase reactants. This observation highlights the need for further studies aimed to evaluate the impact of subjective physician and parent perception of disease remission and of laboratory measures of inflammatory activity on the definition of ID.

A clinical prediction model for estimating the risk of developing uveitis in patients with juvenile idiopathic arthritis.

OBJECTIVE: To build a prediction model for uveitis in children with JIA for use in current clinical practice. METHODS: Data from the international observational Pharmachild registry were used. Adjusted risk factors as well as predictors for JIA-associated uveitis (JIA-U) were determined using multivariable logistic regression models. The prediction model was selected based on the Akaike information criterion. Bootstrap resampling was used to adjust the final prediction model for optimism. RESULTS: JIA-U occurred in 1102 of 5529 JIA patients (19.9%). The majority of patients that developed JIA-U were female (74.1%), ANA positive (66.0%) and had oligoarthritis (59.9%). JIA-U was rarely seen in patients with systemic arthritis (0.5%) and RF positive polyarthritis (0.2%). Independent risk factors for JIA-U were ANA positivity [odds ratio (OR): 1.88 (95% CI: 1.54, 2.30)] and HLA-B27 positivity [OR: 1.48 (95% CI: 1.12, 1.95)] while older age at JIA onset was an independent protective factor [OR: 0.84 (9%% CI: 0.81, 0.87)]. On multivariable analysis, the combination of age at JIA onset [OR: 0.84 (95% CI: 0.82, 0.86)], JIA category and ANA positivity [OR: 2.02 (95% CI: 1.73, 2.36)] had the highest discriminative power among the prediction models considered (optimism-adjusted area under the receiver operating characteristic curve = 0.75). CONCLUSION: We developed an easy to read model for individual patients with JIA to inform patients/parents on the probability of developing uveitis.

Analysis of arthritis flares after achievement of inactive disease with methotrexate monotherapy in juvenile idiopathic arthritis.

OBJECTIVES: To investigate the frequency of arthritis flare and factors affecting occurrence of flare in children with juvenile idiopathic arthritis (JIA) who achieved inactive disease (ID) with methotrexate (MTX) monotherapy. METHODS: A total of 217 patients were included. The modality of treatment discontinuation, time of MTX withdrawal, and disease course were examined retrospectively. For each patient, the first episode of ID after MTX start was evaluated. Patient follow-up was censored at occurrence of flare or at last visit with persistent ID. RESULTS: 170 patients (78.3%) had arthritis flare after a median of 1.6 years, whereas 47 (21.7%) maintained ID until last visit, after a median of 3 years. 54.2% of patients had discontinued MTX after ID, whereas 45.8% were still receiving MTX at the time of study censoring. Among patients who had MTX withdrawn, the median interval between ID and MTX stop was 1.5 years. Occurrence of flare was more common in patients who were still receiving MTX at study censoring than in those who had discontinued MTX (p<0.001). Most patients (78.8%) had MTX tapered over time by increasing the interval between doses. Tapering modality was comparable between patients with flare and persistent ID. Only 7.7% of the patients had a biologic DMARD started at the time of flare. CONCLUSIONS: Our results confirm that children with JIA who achieve ID with MTX monotherapy have a high risk of arthritis flare. The risk of flare was independent of withdrawal strategy. Most flare episodes were not treated with biologic therapy.

Tocilizumab may slow radiographic progression in patients with systemic or polyarticular-course juvenile idiopathic arthritis: post hoc radiographic analysis from two randomized controlled trials.

BACKGROUND: Few clinical trials have investigated the prevention of radiographic progression in children with juvenile idiopathic arthritis treated with antirheumatic drugs. This study aimed to investigate radiographic progression in patients with systemic juvenile idiopathic arthritis (sJIA) and patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with the anti-interleukin-6 receptor antibody tocilizumab for 2 years in the TENDER and CHERISH randomized controlled trials, respectively. METHODS: Standard radiographs of both wrists and both hands in the posteroanterior view were obtained within 4 weeks of baseline and were repeated at weeks 52 ± 4 and 104 ± 4 in both trials. All films were scored by two independent readers using the adapted Sharp-van der Heijde (aSH) and Poznanski scoring methods. Although the Poznanski score indicates bone growth limitation or cartilage growth decrease, which are not the same as joint space narrowing in rheumatoid arthritis, its change reflects damage to cartilage. Therefore, impairment in the Poznanski score as well as the aSH score was considered as a measure of structural joint damage. Radiographic progression was defined as worsening of radiographic scores beyond the smallest detectable difference. RESULTS: Poznanski and aSH scores were available at baseline and at one or more postbaseline time points for 33 and 47 of 112 sJIA patients and 61 and 87 of 188 pcJIA patients, respectively, providing a representative subset of the study populations. The inter-reader and intra-reader agreement intra-class correlation coefficient was > 0.8. Median baseline Poznanski and aSH scores, respectively, were - 2.4 and 24.6 for sJIA patients and - 1.5 and 8.0 for pcJIA patients. Compared with baseline, aSH scores remained stable for all sJIA patients at week 52, whereas 9.4% of sJIA patients had radiographic progression according to Poznanski scores at week 52; at 104 weeks, radiographic progression according to aSH and Poznanski scores was observed in 5.4% and 11.5%, respectively. In pcJIA patients, radiographic progression from baseline at 52 weeks and at 104 weeks was 12.5% and 2.9%, respectively, using aSH scoring and 6.5% and 4%, respectively, using Poznanski scoring. CONCLUSION: Tocilizumab may delay radiographic progression in children with sJIA and children with pcJIA. TRIAL REGISTRATION: Trial registration numbers and dates: TENDER, NCT00642460 (March 19, 2008); CHERISH, NCT00988221 (October 1, 2009).

Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis.

OBJECTIVE: To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. METHODS: The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. RESULTS: A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. CONCLUSION: The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee.

BACKGROUND: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). METHODS: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. RESULTS: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. CONCLUSIONS: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT01399281; ENCePP seal: awarded on 25 November 2011.

Growth and Puberty in Juvenile Dermatomyositis: A Longitudinal Cohort Study.

OBJECTIVE: To study growth and puberty in a multinational longitudinal prospective cohort of children with juvenile dermatomyositis (DM). METHODS: Children from 31 countries who were ages <18 years and had juvenile DM in active phase were studied, and analyses of height, weight, and pubertal development were conducted in those who had follow-up visits during a 2-year period and for whom anthropometric data was available. RESULTS: A total of 196 of 275 children (71%) were included. We found a significant reduction in parent-adjusted height Z score over time in female patients (P < 0.0001) and male patients (P = 0.001), but with catch-up growth at the final study visit. Median body mass index Z score peaked at 6 months (P < 0.0001) and was still significantly above baseline at the final study visit, which was at a median of 26 months after baseline (P = 0.007), with no difference between sexes. Female patients with a disease duration ≥12 months after onset had significantly lower parent-adjusted height Z score (P = 0.002) and no 2-year catch-up growth. At the final study visit, growth failure was seen in 20 of 97 female patients (21%) and in 11 of 73 male patients (15%). Height deflection (∆height Z score less than -0.25/year) was observed in 29 of 116 female patients (25%) and 25 of 80 male patients (31.3%). Delayed puberty was seen in 20 of 55 female patients (36.4%) and in 11 of 31 male patients (35.5%). Children in early pubertal stage at baseline had the highest risk of growth failure. CONCLUSION: Juvenile DM in the active phase and/or its treatment has a significant impact on growth and puberty in affected children. Children with recent onset of puberty or previous growth failure have the highest risk of delayed pubertal development and further growth retardation.

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

OBJECTIVE: To investigate the effect of morning stiffness (MS) on parent disease perception in children with juvenile idiopathic arthritis (JIA) with clinically inactive disease (CID). METHODS: 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. RESULTS: 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. CONCLUSION: Our results suggest that a change in 2011 CID criteria to require absence of MS should be considered.

A prediction rule for lack of achievement of inactive disease with methotrexate as the sole disease-modifying antirheumatic therapy in juvenile idiopathic arthritis.

BACKGROUND: To investigate the frequency of achievement of inactive disease (ID) in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX) as the sole disease-modifyng antirheumatic (DMARD) therapy and to develop a prediction model for lack of attainment of ID. METHODS: The clinical charts of consecutive patients started with MTX as the sole DMARD between 2000 and 2013 were reviewed. Patient follow-up was censored at first episode of ID or, in case ID was not reached, at last follow-up visit or when a biologic DMARD was prescribed. The characteristic at MTX start of patients who achieved or did not achieve ID were compared with univariate and multivariable analyses. Regression coefficients (ß) of variables that entered the best-fitting logistic regression model were converted and summed to obtain a "prediction score" for lack of achievement of ID. RESULTS: A total of 375 patients were included in the study. During MTX administration, 8.8% were given systemic corticosteroids and 44.1% intra-articular corticosteroids. After MTX start, 229 (61%) patients achieved ID after a median of 1.7 years, whereas 146 patients (39%) did not reach ID after a median of 1.2 years. On multivariable analysis, independent correlations with lack of achievement of ID were identified for the disease categories of systemic arthritis, enthesitis-related arthritis (ERA) and polyarthritis and C-reactive protein (CRP) >  1.4 mg/dl. The prediction score ranged from 0 to 3 and its cutoff that discriminated best between patients who achieved or did not achieve ID was > 0.5. The categories of systemic arthritis or ERA, both of which had a score greater than 0.5, were sufficient alone to predict a lower likelihood to reach ID. Polyarthritis and increased CRP, whose score was 0.5, assumed a predictive value only when present in association. CONCLUSION: A conventional treatment regimen based on MTX as the sole DMARD led to achievement of ID in a sizeable proportion of children with JIA. Our findings help to outline the characteristics of patients who may deserve a synthetic DMARD other than MTX or the introduction of a biologic DMARD from disease outset.