Quantifying hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing tumour necrosis factor-alfa inhibitors in juvenile idiopathic arthritis.

OBJECTIVE: To quantify differences in hospital-associated costs, and accompanying travel costs and productivity losses, before and after withdrawing TNFi in JIA patients. METHODS: Retrospective analysis of prospectively collected data from electronic medical records of paediatric JIA patients treated with TNFi, which were either immediately discontinued, spaced (increased treatment interval) or tapered (reduced subsequent doses). Costs of hospital-associated resource use (consultations, medication, radiology procedures, laboratory testing, procedures under general anaesthesia, hospitalisation) and associated travel costs and productivity losses were quantified during clinically inactive disease until TNFi withdrawal (pre-withdrawal period) and compared with costs during the first and second year after withdrawal initiation (first and second year post-withdrawal). RESULTS: Fifty-six patients were included of whom 26 immediately discontinued TNFi, 30 spaced and zero tapered. Mean annual costs were €9,165/patient on active treatment (pre-withdrawal) and decreased significantly to €5,063/patient (-44.8%) and €6,569/patient (-28.3%) in the first and second year post-withdrawal, respectively (p< 0.05). Of these total annual costs, travel costs plus productivity losses were €834/patient, €1,180/patient, and €1,320/patient, in the three periods respectively. Medication comprised 80.7%, 61.5% and 72.4% of total annual costs in the pre-withdrawal, first, and second year post-withdrawal period, respectively. CONCLUSION: In the first two years after initiating withdrawal, the total annual costs are decreased compared with the pre-withdrawal period. However, cost reductions were lower in the second year compared with the first year post-withdrawal, primarily due to restarting or intensifying biologics. To support biologic withdraw decisions, future research should assess the full long-term societal cost impacts, and include all biologics.

Costs of Hospital-Associated Care for Patients With Juvenile Idiopathic Arthritis in the Dutch Health Care System.

OBJECTIVE: The aim of this study was to quantify costs of hospital-associated care for juvenile idiopathic arthritis (JIA), provide insights in patient-level variation in costs, and investigate costs over time from the moment of JIA diagnosis. Results were reported for all JIA patients in general and by subtype. METHODS: This study was a single-center, retrospective analysis of prospective data from electronic medical records of children with JIA, ages 0-18 years, between April 1, 2011 and March 31, 2019. Patient characteristics (age, sex, JIA subtype) and hospital-based resource use (consultations, medication, radiology procedures, laboratory testing, surgeries, emergency department [ED] visits, hospital stays) were extracted and analyzed. Unit prices were obtained from Dutch reimbursement lists and pharmaceutical and hospital list prices. RESULTS: The analysis included 691 patients. The mean total cost of hospital care was €3,784/patient/year, of which €2,103 (55.6%) was attributable to medication. Other costs involved pediatric rheumatologist visits (€633/patient/year [16.7%]), hospital stays (€439/patient/year [11.6%]), other within-hospital specialist visits (€324/patient/year [8.6%]), radiology procedures (€119/patient/year [3.1%]), laboratory tests (€114/patient/year [3.0%]), surgeries (€46/patient/year [1.2%]), and ED visits (€6/patient/year [0.2%]). Mean annual total costs varied between JIA subtypes and between individuals and were the highest for systemic JIA (€7,772/patient/year). Over the treatment course, costs were the highest in the first month after JIA diagnosis. CONCLUSION: Hospital care costs of JIA vary substantially between individuals, between subtypes, and over the treatment course. The highest annual costs were for systemic JIA, primarily attributable to medication (i.e., biologics). Costs of other hospital-associated care were comparable regardless of subtype.

Evaluation of Real-World Healthcare Resource Utilization and Associated Costs in Children with Juvenile Idiopathic Arthritis: A Canadian Retrospective Cohort Study.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease, whose multifaceted care path can lead to significant expenditure for the healthcare system. We aim to assess the real-world healthcare resource use (HCRU) and associated cost for children with JIA in a single center in Canada. METHODS: A single-center consecutive cohort of newly diagnosed patients with JIA attending the pediatric rheumatology clinic from 2011 to 2019 was identified using an administrative data algorithm and electronic medical charts. HCRU was estimated from six administrative health databases that included hospital admissions, emergency, outpatient care, practitioners' visits, medication, and laboratory and imaging tests. Costs were assigned using appropriate sources. We reported the yearly overall and JIA-associated HCRU and costs 5 years prior to and 6 years after the first visit to the pediatric rheumatologist. The Zhao and Tian estimator was used to calculate cumulative mean costs over a 6-year timeframe. Results were stratified by disease subtype. RESULTS: A total of 389 patients were identified. The yearly total overall mean costs per patient ranged between $804 and $4460 during the 5 years prior to the first visit to the pediatric rheumatologist and $8529 and $10,651 for the 6 years after. Medication cost, driven by use of biologic therapies, and outpatient visits were the greatest contributor to the total cost. The overall cumulative mean cost for 6 years of care was $48,649 per patient, while the JIA-associated cumulative mean cost was $26,820 per patient. During the first year of rheumatology care, systemic onset JIA had the highest cumulative mean overall cost, while oligoarticular JIA had the lowest cumulative mean cost. CONCLUSION: The care pathway for children with JIA can be expensive, and complex-and varies by JIA subtype. Although the yearly total mean cost per patient was constant, the distribution of costs changes over time with the introduction of biologic therapies later in the care pathway. This study provides a better understanding of the JIA costs profile and can help inform future economic studies.

Monitoring patients with juvenile idiopathic arthritis using health-related quality of life.

BACKGROUND: Pediatric patients with juvenile idiopathic arthritis (JIA) are at risk for a lower health-related quality of life compared to their healthy peers. Remote monitoring of health-related quality of life using electronic patient-reported outcomes could provide important information to treating physicians. The aim of this study was to investigate if self-assessment with the EuroQol five-dimensional 'youth' questionnaire with five levels (EQ-5D-Y-5 L) inside a mobile E-health application could identify JIA patients in need of possible treatment adjustments. METHODS: The EQ-5D-Y-5 L was completed via a mobile application (Reuma2Go) between October 2017 and January 2019. The clinical juvenile arthritis disease activity score with 71 joint count (cJADAS-71) was reported at every corresponding visit as reference for disease activity. Previously described cJADAS-71 thresholds were used to identify patients in possible need of treatment adjustments. Discriminatory power of the EQ-5D-Y-5 L was assessed by ROC-curves and diagnostic characteristics. RESULTS: Sixty-eight JIA patients completed the EQ-5D-Y-5 L questionnaire. Median cJADAS-71 indicated low disease activity overall in the studied population. ROC curves and diagnostic characteristics demonstrated that self-assessment with the EQ-5D-Y-5 L could distinguish between patients with inactive disease (or minimal disease activity) and moderate to high disease activity with good accuracy (87%), sensitivity (85%), specificity (89%) and negative predictive value (86%). CONCLUSIONS: Results demonstrate that the EQ-5D-Y-5 L was able to identify JIA patients in need of possible treatment adjustments in our studied population. Remote monitoring of health-related quality of life and patient-reported outcomes via E-health applications could provide important additional information to determine the frequency of clinical visits, assess therapeutic efficacy and guide treat-to-target strategies in pediatric patients with JIA.

Costs of medication use among patients with juvenile idiopathic arthritis in the Dutch healthcare system.

Background: This study aims to quantify medication costs in juvenile idiopathic arthritis (JIA), based on subtype.Research design and methods: This study is a single-center, retrospective analysis of prospective data from electronic medical records of JIA patients, aged 0-18 years between 1 April 2011 and 31 March 2019. Patient characteristics (age, gender, subtype) and medication use were extracted. Medication use and costs were reported as: 1) mean total annual costs; 2) between-patient heterogeneity in these costs; 3) duration of medication use; and, 4) costs over the treatment course.Results: The analysis included 691 patients. Mean total medication costs were €2,103/patient/year, including €1,930/patient/year (91.8%) spent on biologicals. Costs varied considerably between subtypes, with polyarticular rheumatoid-factor positive and systemic JIA patients having the highest mean costs (€5,020/patient/year and €4,790/patient/year, respectively). Mean annual medication costs over the patient's treatment course ranged from <€1,000/year (71.1% of patients) to >€11,000/year (2.5% of patients). Etanercept and adalimumab were the most commonly used biologicals. Cost fluctuations over the treatment course were primarily attributable to biological use.Conclusions: Polyarticular rheumatoid-factor positive and systemic JIA patients had the highest mean total annual medication costs, primarily attributable to biologicals. Costs varied considerably between subtypes, individuals, and over the treatment course.

Seeking the state of the art in standardized measurement of health care resource use and costs in juvenile idiopathic arthritis: a scoping review.

BACKGROUND: This study aims to describe current practice in identifying and measuring health care resource use and unit costs in economic evaluations or costing studies of juvenile idiopathic arthritis (JIA). METHODS: A scoping review was conducted (in July 2018) in PubMed and Embase to identify economic evaluations, costing studies, or resource utilization studies focusing on patients with JIA. Only English language peer-reviewed articles reporting primary research were included. Data from all included full-text articles were extracted and analysed to identify the reported health care resource use items. In addition, the data sources used to obtain these resource use and unit costs were identified for all included articles. RESULTS: Of 1176 unique citations identified by the search, 20 full-text articles were included. These involved 4 full economic evaluations, 5 cost-outcome descriptions, 8 cost descriptions, and 3 articles reporting only resource use. The most commonly reported health care resource use items involved medication (80%), outpatient and inpatient hospital visits (80%), laboratory tests (70%), medical professional visits (70%) and other medical visits (65%). Productivity losses of caregivers were much more often incorporated than (future) productivity losses of patients (i.e. 55% vs. 15%). Family borne costs were not commonly captured (ranging from 15% for school costs to 50% for transportation costs). Resource use was mostly obtained from family self-reported questionnaires. Estimates of unit costs were mostly based on reimbursement claims, administrative data, or literature. CONCLUSIONS: Despite some consistency in commonly included health care resource use items, variability remains in including productivity losses, missed school days and family borne costs. As these items likely substantially influence the full cost impact of JIA, the heterogeneity found between the items reported in the included studies limits the comparability of the results. Therefore, standardization of resource use items and unit costs to be collected is required. This standardization will provide guidance to future research and thereby improve the quality and comparability of economic evaluations or costing studies in JIA and potentially other childhood diseases. This would allow better understanding of the burden of JIA, and to estimate how it varies across health care systems.

Phenotypic variability and disparities in treatment and outcomes of childhood arthritis throughout the world: an observational cohort study.

BACKGROUND: To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. METHODS: In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. FINDINGS: Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33·0%] of 379 patients) and enthesitis-related arthritis (113 [29·8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56·7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31·5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19·1%] of 845 patients) and southern Europe (450 [18·8%] of 2400) and lowest in Latin America (54 [6·4%] of 849), Africa and Middle East (71 [5·9%] of 1209), and southeast Asia (19 [5·0%] of 379). Median age at disease onset was lower in southern Europe (3·5 years, IQR 1·9-7·3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. INTERPRETATION: Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lower-resource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. FUNDING: IRCCS Istituto Giannina Gaslini.

The European network for care of children with paediatric rheumatic diseases: care across borders.

OBJECTIVES: To provide an overview of the paediatric rheumatology (PR) services in Europe, describe current delivery of care and training, set standards for care, identify unmet needs and inform future specialist service provision. METHODS: An online survey was developed and presented to national coordinating centres of the Paediatric Rheumatology International Trials Organisation (PRINTO) (country survey) and to individual PR centres (centre and disease surveys) as a part of the European Union (EU) Single Hub and Access point for paediatric Rheumatology in Europe project. The survey contained components covering the organization of PR care, composition of teams, education, health care and research facilities and assessment of needs. RESULTS: Response rates were 29/35 (83%) for country surveys and 164/288 (57%) for centre surveys. Across the EU, approximately one paediatric rheumatologist is available per million population. In all EU member states there is good access to specialist care and medications, although biologic drug availability is worse in Eastern European countries. PR education is widely available for physicians but is insufficient for allied health professionals. The ability to participate in clinical trials is generally high. Important gaps were identified, including lack of standardized clinical guidelines/recommendations and insufficient adolescent transition management planning. CONCLUSION: This study provides a comprehensive description of current specialist PR service provision across Europe and did not reveal any major differences between EU member states. Rarity, chronicity and complexity of diseases are major challenges to PR care. Future work should facilitate the development, dissemination and implementation of standards of care, treatment and service recommendations to further improve patient-centred health care across Europe.

International Consortium for Health Outcome Measurement Set of Outcomes That Matter to People Living With Inflammatory Arthritis: Consensus From an International Working Group.

OBJECTIVE: The implementation of value-based health care in inflammatory arthritis requires a standardized set of modifiable outcomes and risk-adjustment variables that is feasible to implement worldwide. METHODS: The International Consortium for Health Outcomes Measurement (ICHOM) assembled a multidisciplinary working group that consisted of 24 experts from 6 continents, including 6 patient representatives, to develop a standard set of outcomes for inflammatory arthritis. The process followed a structured approach, using a modified Delphi process to reach consensus on the following decision areas: conditions covered by the set, outcome domains, outcome measures, and risk-adjustment variables. Consensus in areas 2 to 4 were supported by systematic literature reviews and consultation of experts. RESULTS: The ICHOM Inflammatory Arthritis Standard Set covers patients with rheumatoid arthritis (RA), axial spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). We recommend that outcomes regarding pain, fatigue, activity limitations, overall physical and mental health impact, work/school/housework ability and productivity, disease activity, and serious adverse events be collected at least annually. Validated measures for patient-reported outcomes were endorsed and linked to common reporting metrics. Age, sex at birth, education level, smoking status, comorbidities, time since diagnosis, and rheumatoid factor and anti-citrullinated protein antibody lab testing for RA and JIA should be collected as risk-adjustment variables. CONCLUSION: We present the ICHOM inflammatory arthritis Standard Set of outcomes, which enables health care providers to implement the value-based health care framework and compare outcomes that are important to patients with inflammatory arthritis.

The Dutch version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Dutch language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 209 JIA patients (14.3% systemic, 39.7% oligoarticular, 25.8% RF negative polyarthritis, 20.2% other categories) and 107 healthy children were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Dutch version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

The burden of systemic juvenile idiopathic arthritis for patients and caregivers: an international survey and retrospective chart review.

OBJECTIVES: To investigate the burden of systemic juvenile idiopathic arthritis (SJIA) on health-related quality of life (HRQOL) and resource use of patients and caregivers (families) on biologic therapy. METHODS: This international study assessed SJIA burden in patients on biologics, using a caregiver questionnaire and retrospective chart review. Validated measures included: Child Health Questionnaire Parent-Form 50 (CHQ-PF50), 36-Item Short-Form Health Survey (SF-36v2) and Work Productivity and Activity Impairment questionnaire: Specific Health Problem (WPAI:SHP). Caregivers completed function, treatment satisfaction and resource utilisation questions. RESULTS: Sixty-one biologic treated patients participated (12 anakinra, 25 canakinumab, 24 tocilizumab). Mean age at diagnosis and survey completion was 6.4 and 11.3 years, respectively. Mean (±SD: standard deviation) CHQ-PF50 physical (PhS) and psychosocial (PsS) summary scores were significantly lower in SJIA patients than a normative population (PhS: 40.0±18.2 vs. 53.0±8.8; PsS: 46.6±11.3 vs. 51.2±9.1) as was caregivers' mean SF-36v2 mental component score (MCS; 46.2±10.7 vs. 50.0±10). Assistive devices were required by 54%; 20% required home/car alterations. According to caregivers, biologic treatment completely improved SJIA symptoms in 48% on canakinumab or tocilizumab and 32% on anakinra. Over 2 months, patients missed 2.9 school days due to SJIA (10% yearly loss). Caregivers lost 25 work days annually and 27.5 days of productivity (WPAI-SHP: mean absenteeism 10%; presenteeism 11%). Yearly SJIA travel/treatment costs averaged $1,130. CONCLUSIONS: SJIA patients on biologic therapy experience HRQOL impairment, caregivers' mental well-being suffers and productivity losses and expenses are incurred. Therapeutic interventions that reduce the burden of SJIA are required.

Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases.

Hematopoietic stem cell transplantation (HSCT) has evolved for >20 years as a specific treatment of patients with autoimmune disease (AD). Using European Society for Blood and Marrow Transplantation registry data, we summarized trends and identified factors influencing activity and outcomes in patients with AD undergoing first autologous HSCT (n = 1951; median age, 37 years [3-76]) and allogeneic HSCT (n = 105; median age, 12 years [<1-62]) in 247 centers in 40 countries from 1994 to 2015. Predominant countries of activity were Italy, Germany, Sweden, the United Kingdom, The Netherlands, Spain, France, and Australia. National activity correlated with the Human Development Index (P = .006). For autologous HSCT, outcomes varied significantly between diseases. There was chronological improvement in progression-free survival (PFS, P < 10-5), relapse/progression (P < 10-5), and nonrelapse mortality (P = .01). Health care expenditure was associated with improved outcomes in systemic sclerosis and multiple sclerosis (MS). On multivariate analysis selecting adults for MS, systemic sclerosis, and Crohn disease, better PFS was associated with experience (≥23 transplants for AD, P = .001), learning (time from first HSCT for AD ≥6 years, P = .01), and Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation accreditation status (P = .02). Despite improved survival over time (P = .02), allogeneic HSCT use remained low and largely restricted to pediatric practice. Autologous HSCT has evolved into a treatment modality to be considered alongside other modern therapies in severe AD. Center experience, accreditation, interspecialty networking, and national socioeconomic factors are relevant for health service delivery of HSCT in AD.

Prevalence of Severe Fatigue Among Adolescents With Pediatric Rheumatic Diseases.

OBJECTIVE: To determine the prevalence of severe fatigue and fatigue-related limitations among adolescents with juvenile idiopathic arthritis (JIA) and other pediatric rheumatic diseases (PRDs). In addition, we assessed the effect of disease activity and pain on the severity of fatigue. METHODS: This cross-sectional study included 175 patients (ages 10-18 years) who visited the pediatric rheumatology and immunology outpatient clinic at Wilhelmina Children's Hospital from April through July 2013. Patients completed validated questionnaires regarding fatigue, physical functioning, and school attendance. Disease activity in JIA patients was measured using the Juvenile Arthritis Disease Activity Score including 27 joints. The results were compared against a healthy control group. RESULTS: The prevalence of severe fatigue among patients with PRDs was 25.1%, which was significantly higher than among the healthy control group (P < 0.001). Fatigued patients had significantly lower levels of physical functioning compared to nonfatigued patients (62.1% versus 89.0%, respectively; P < 0.001) and a significantly higher percentage of school absences (21.2% versus 11.6%, respectively; P = 0.005). Among JIA patients, the level of pain was significantly correlated with fatigue. Finally, disease activity was not a predictor for fatigue. CONCLUSION: Fatigue is a common problem among teenagers with PRDs, with a higher prevalence among these patients than in the general population. Severe fatigue leads to significant impairments, including increased school absences and decreased physical functioning. Interestingly, fatigue was associated with pain, but not with the disease activity. Therefore, in this patient population, fatigue may be a promising therapeutic target for improving functioning, school attendance, and possibly pain as well.

Assessment of disease activity by patients with juvenile idiopathic arthritis and the parents compared to the assessment by pediatric rheumatologists.

BACKGROUND: Self assessment of arthritis is important for recognition of disease activity and early initiation of therapy. Proper interpretation of physical symptoms is necessary for this. The purpose was to investigate the assessment by patients and parents of disease activity in juvenile idiopathic arthritis (JIA) and to compare their assessments to rheumatologists' assessments. METHODS: Patients and parents assessed 69 joints on a paper homunculus and marked each joint with a different color according to presumed presence of disease: active disease (AD), doubt, and non-active disease (NAD). Their assessments were compared to the rheumatologists' assessments. If patients and/or parents marked an inflamed joint, it counted as AD. Pain, functional impairment, and disease duration were analyzed to differentiate more precise between true and false positive and true and false negative assessments. RESULTS: We collected assessments of 113 patients and/or parents. AD was assessed 54 times, 33 of which were true positives. NAD was assessed 23 times, 22 of which were true negatives. Doubt was expressed 36 times, 9 of which were assessed by the rheumatologist as AD. Sensitivity and specificity of AD was 0.77 and 0.31. Pain and functional impairment scored highest in AD, intermediate in doubt, and lowest in NAD. CONCLUSION: Patients and/or parents seldom missed arthritis but frequently overestimated disease activity. Pain, functional impairment, disease duration, gender, and age did not differentiate between true and false positives for. Patients perceived JIA as active if they experienced pain and functional impairment. To reduce overestimation of the presence of AD we need to improve their understanding of disease activity by teaching them to distinguish between primary symptoms of JIA and symptoms like pain and functional impairment.

Performance of Birmingham Vasculitis Activity Score and disease extent index in childhood vasculitides.

OBJECTIVES: To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. METHODS: Patients fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schönlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis ≤3 months were extracted from the PRINTO database. The performance of the BVAS and DEI were examined by assessing convergent validity, the pattern of disease involvement, and responsiveness. We also evaluated alternative unweighted scoring methods for both tools. RESULTS: The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 c-WG and 22 c-TA. The median age at diagnosis was 6.9 years (6.6-12) and median delay in making the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A strong correlation was found between the BVAS and DEI (rs=0.78) while correlation with the physician global assessment was moderate (rs=0.48) with BVAS and poor with DEI (rs=0.25). Both the BVAS and DEI sub-scores and total scores were able to descrive the disease involvement in the 4 childhood vasculitides. Responsiveness was large (>1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. CONCLUSIONS: This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides.

The efficacy and safety of interleukin-1-receptor antagonist anakinra in the treatment of systemic juvenile idiopathic arthritis.

IMPORTANCE OF THE FIELD: Systemic juvenile idiopathic arthritis (sJIA) is a debilitating childhood disease presenting with fever, rash and arthritis. Current therapy consisting mainly of corticosteroids, NSAIDs and methotrexate, can be inefficient and is often accompanied by many serious adverse events. Although an IL-1 receptor antagonist (anakinra) seems to be very efficient in case series, it is not registered for use in sJIA. Pediatric rheumatologists all over the world are having a hard time to convince insurance companies to approve off-label use of this drug for their sJIA patients. AREAS COVERED IN THIS REVIEW: Using the MeSH terms 'Arthritis Juvenile Rheumatoid' and 'Interleukin 1 Receptor Antagonist Protein', we searched MEDLINE, EMBASE and reference lists of selected articles. This review is largely based on manuscripts from 2005 to 2010 and abstracts presented at the major (pediatric) rheumatology congresses. WHAT THE READER WILL GAIN: This review summarizes the data of 140 children with sJIA treated with anakinra and enables an understanding in the benefit-risk profile of anakinra in sJIA patients. TAKE HOME MESSAGE: Anakinra has shown to be a very efficient and quick acting medicine in reducing symptoms even in therapy-resistant sJIA patients with typically poor outcomes.

Development of a standardized method of assessment of radiographs and radiographic change in juvenile idiopathic arthritis: introduction of the Dijkstra composite score.

OBJECTIVE: To evaluate the sensitivity to change of a newly developed radiologic assessment tool, the Dijkstra score, and to develop a numeric composite score and progressor classification scheme to apply in juvenile idiopathic arthritis (JIA) trials. METHODS: A placebo-controlled trial of sulfasalazine (SSZ) in patients with oligoarticular- and polyarticular-onset JIA yielded the data for this study. Data were obtained from 418 sets of radiographs of the clinically involved and contralateral joints (at study entry and at 6 months' followup) from 66 JIA patients. The Dijkstra score assesses the presence or absence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. These signs were combined in the Dijkstra composite score, to assess inflammation (DI), growth (DG), and damage (DD). Progression was defined as an increase in either the DG or the DD score. Scores were evaluated among all radiographs, a standard set of films (hand, foot, and knee), and per patient. All scores were used to explore differences between the 2 treatment groups. RESULTS: Over time, 58% of joints remained normal, 23% remained abnormal but stable, 14% showed an increase in signs, and 5% showed a decrease in signs. Of the 66 JIA patients, 12% had normal radiographic findings throughout followup, 27% showed abnormalities at some sites without change, and 61% showed change in at least 1 site. Changes in the DI, DG, and DD scores varied considerably per type of joint and occurred most frequently in joints of the standard set. DI and DG scores changed most often in the knees, while DD scores changed primarily in the hands and feet. The disease course in 8% of joints was classified as progressive. Films of SSZ-treated patients, versus the placebo group, showed less deterioration by the DD scores (P = 0.04), and the disease course was more often classified as nonprogressive in the SSZ group (P = 0.037). When progressors were defined as those who had at least one radiograph showing progression, significantly more placebo-treated patients were considered progressors (P = 0.046). CONCLUSION: In this trial data set, the Dijkstra composite score and the resulting progressor classification system are comprehensive and feasible tools that are sensitive to change and discriminate between clinical situations. They should now be tested by other investigators and in other data sets.

Radiologic features in juvenile idiopathic arthritis: a first step in the development of a standardized assessment method.

OBJECTIVE: To describe radiologic features of patients with juvenile idiopathic arthritis (JIA) in a standardized manner, to test the reliability and feasibility of this description, and to correlate these features with clinical signs as a first step in the development of a standardized assessment method. METHODS: The placebo-controlled study of sulfasalazine in patients with oligoarticular, extended oligoarticular, and polyarticular JIA performed by the Dutch Juvenile Idiopathic Arthritis Study Group yielded the data for this study. All trial entry radiographs (clinically involved joints and contralateral joints) were scored (in consensus by a skeletal radiologist and pediatric rheumatologist) for the presence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. RESULTS: Data on 67 of 69 patients were analyzed. The mean age was 9.1 years (range 2.5-17.6 years), and the median disease duration was 24 months (range 5-176 months). Thirteen percent of the patients were IgM rheumatoid factor (IgM-RF) positive, and 16% were HLA-B27 positive. All 68 clinically evaluated joints were included in the maximum of 19 radiographed joints (or joint groups) per patient. The mean number of radiographed joints per patient was 7 (range 2-15); knees, hands, ankles, and feet were most frequently affected. Fifty-eight patients (87%) had radiologic abnormalities in at least one joint (soft-tissue swelling in 63% of patients, growth disturbances in 48%, joint space narrowing in 28%, and erosions in 15%). In total, half of the radiographs of the clinically involved joints showed radiologic abnormalities, including two-thirds of the radiographs of the clinically affected hands and knees. Univariate analysis revealed a good correlation between the overall articular (clinical) severity and the presence of radiologic abnormalities (odds ratio [OR] 1.38, P < 0.0001). Multivariate analysis showed increased ORs for the presence of radiologic abnormalities and IgM-RF positivity (OR 4.6, P = 0.005) or HLA-B27 positivity (OR 3.0, P = 0.004). In general, reproducibility of the radiologic scoring method was good (mean kappa coefficient of 0.74 [range 0.40-0.86]), although there were scoring discrepancies for swelling, osteopenia, and growth disturbances. The scoring took 10-20 minutes per patient. CONCLUSION: Our model of describing and scoring radiologic abnormalities of radiographed joints in JIA was feasible, mostly reproducible, correlated well with the overall articular severity score, and added substantial new information not available on clinical examination.