Roberta A. Berard

The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort

Objective To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments. Methods Children newly diagnosed with JIA at 16 Canadian paediatric rheumatology centres from 2005 to 2010 were included. Kaplan–Meier survival curves for each JIA category were used to estimate probability of ever attaining an active joint count of 0, inactive disease (no active joints, no extraarticular manifestations and a physician global assessment of disease activity <10 mm), disease remission (inactive disease >12 months after discontinuing treatment) and of receiving specific treatments. Results In a cohort of 1104 children, the probabilities of attaining an active joint count of 0 exceeded 78% within 2 years in all JIA categories. The probability of attaining inactive disease exceeded 70% within 2 years in all categories, except for RF-positive polyarthritis (48%). The probability of discontinuing treatment at least once was 67% within 5 years. The probability of attaining remission within 5 years was 46–57% across JIA categories except for polyarthritis (0% RF-positive, 14% RF-negative). Initial treatment included joint injections and non-steroidal anti-inflammatory drugs for oligoarthritis, disease-modifying antirheumatic drugs (DMARDs) for polyarthritis and systemic corticosteroids for systemic JIA. Conclusions Most children with JIA managed with contemporary treatments attain inactive disease within 2 years of diagnosis and many are able to discontinue treatment. The probability of attaining remission within 5 years of diagnosis is about 50%, except for children with polyarthritis.

Hemolytic anemia following intravenous immunoglobulin therapy in patients treated for Kawasaki disease: a report of 4 cases

BackgroundHemolytic anemia is a rare but reported side effect of intravenous immunoglobulin (IVIG) therapy. The risk of significant hemolysis appears greater in those patients who receive high dose IVIG. The etiology is multifactorial but may relate to the quantity of blood group antibodies administered via the IVIG product.FindingsWe describe 4 patients with significant hemolytic anemia following treatment with IVIG for Kawasaki disease (KD). Direct antibody mediated attack as one of the mechanisms for hemolysis, in this population, is supported by the demonstration of specific blood group antibodies in addition to a positive direct antiglobulin test in our patients.ConclusionsClinicians should be aware of this complication and hemoglobin should be closely monitored following high dose IVIG therapy.

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

Objective To 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. Methods We studied children in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) prospective inception cohort. A flare was defined as a recurrence of disease manifestations after attaining inactive disease and was called significant if it required intensification of treatment. Probability of first flare was calculated with Kaplan–Meier methods, and associated features were identified using Cox regression. Results 1146 children were followed up a median of 24 months after attaining inactive disease. We observed 627 first flares (54.7% of patients) with median active joint count of 1, physician global assessment (PGA) of 12 mm and duration of 27 weeks. Within a year after attaining inactive disease, the probability of flare was 42.5% (95% CI 39% to 46%) for any flare and 26.6% (24% to 30%) for a significant flare. Within a year after stopping treatment, it was 31.7% (28% to 36%) and 25.0% (21% to 29%), respectively. A maximum PGA >30 mm, maximum active joint count >4, rheumatoid factor (RF)-positive polyarthritis, antinuclear antibodies (ANA) and receiving disease-modifying antirheumatic drugs (DMARDs) or biological agents before attaining inactive disease were associated with increased risk of flare. Systemic JIA was associated with the lowest risk of flare. Conclusions In this real-practice JIA cohort, flares were frequent, usually involved a few swollen joints for an average of 6 months and 60% led to treatment intensification. Children with a severe disease course had an increased risk of flare.

What Matters Most for Patients, Parents, and Clinicians in the Course of Juvenile Idiopathic Arthritis? A Qualitative Study

Objective. To assess which clinical features are most important for patients, parents, and clinicians in the course of juvenile idiopathic arthritis (JIA). Methods. Forty-nine people participated in 6 audience-specific focus group discussions and 112 reciprocal interviews in 3 Canadian cities. Participants included youth with JIA, experienced English- and French-speaking parents, novice parents (< 6 mos since diagnosis), pediatric rheumatologists, and allied health professionals. Participants discussed the importance of 34 JIA clinical features extracted from medical literature. Transcripts and interview reports underwent qualitative analysis to establish relative priorities for each group. Results. Most study participants considered medication requirements, medication side effects, pain, participant-defined quality of life, and active joints as high priority clinical features of JIA. Active joint count was the only American College of Rheumatology core variable accorded high or medium priority by all groups. Rheumatologists and allied health professionals considered physician global assessment as high priority, but it had very low priority for patients and parents. The parent global assessment was considered high priority by clinicians, medium to high by parents, and low by patients. Child Health Assessment Questionnaire scores were considered low priority by patients and parents, and moderate or high by clinicians. The number of joints with limited motion was given low to very low priority by all groups. Parents gave high priority to arthritis flares. Conclusion. If our findings are confirmed, medication requirements, medication side effects, pain, participant-defined quality of life, and active joint counts should figure prominently in describing the course of JIA.

Approach to the Child with Joint Inflammation

Arthritis is manifested as a swollen joint having at least 2 of the following conditions: limited range of motion, pain on movement, or warmth overlying the joint. This article discusses an approach to the evaluation of a child with arthritis of one (mono) or several (poly) joints.

Etanercept (Enbrel) in the treatment of juvenile idiopathic arthritis

Introduction: Juvenile idiopathic arthritis (JIA) is a relatively common multidimensional and heterogeneous chronic disease of childhood. Children with JIA are at risk for significant morbidity in terms of joint damage, impairments in physical function and health-related quality of life. Outcomes for children with JIA have significantly improved with the use of biologic therapies in the past 15 years, with the most clinical experience being with etanercept. Areas covered: Basic pharmacokinetic and pharmacodynamic data for etanercept will be highlighted. This article will review the clinical trials and open-label registry data for the efficacy and safety of etanercept for use in JIA. Expert opinion: Etanercept is very effective for the treatment of JIA. Data from clinical trials and open-label studies support its clinical efficacy in 80% of patients which appears to be sustained over several years for the majority of treated patients. The safety profile is also acceptable with a serious adverse event rate of 0.03 – 0.12 per patient-year. Further research is needed to evaluate any possible link between biologic therapy, JIA and malignancy, to obtain more long-term safety data, and to document improvements in quality of care and cost-benefit for associated with biologic therapies which may additionally assist in access to these medications. Further, identification of potential clinical or laboratory markers allowing for prediction of response and timing of starting and cessation of this biologic therapy are urgently required.

Description of active joint count trajectories in juvenile idiopathic arthritis.

Objective. To describe the trajectories of longitudinal joint disease activity in juvenile idiopathic arthritis (JIA), and to examine associations of clinical and laboratory characteristics with the identified trajectories. Methods. A retrospective cohort study at 2 Canadian centers was performed. The longitudinal trajectories of active joint counts were described in a proof-of-concept study using a latent growth curve analysis. Baseline patient characteristics were compared across trajectory groups. Results. Data were analyzed on 659 children diagnosed with JIA between March 1980 and September 2009. The median age at diagnosis was 10.0 years (interquartile range 3.7–13.4) and 61% (402/659) were female. The International League of Associations for Rheumatology (ILAR) diagnoses were as follows: oligoarthritis (36%), enthesitis-related arthritis (20%), rheumatoid factor (RF)-negative polyarthritis (13%), undifferentiated arthritis (12%), psoriatic arthritis (8%), systemic arthritis (7%), and RF-positive polyarthritis (4%). Based on the trajectories of their active joint counts, the 659 patients were each classified in 1 of 5 latent classes (which can be described as high decreasing, moderate increasing, persistent moderate, persistent low, and minimal joint activity). These latent classes were clinically and statistically distinct from the ILAR categories. Conclusion. In this proof-of-concept study, in which we used an analytic methodology in a novel way, we identified 5 clinically and statistically distinct trajectories of disease course. The subsets of patients within each class were different from those described by the ILAR classification criteria. This successful application of this method supports its use in a chronic disease with a fluctuating course such as JIA. These methods should be expanded for the purposes of predictive modeling.

Treating juvenile idiopathic arthritis to target: recommendations of an international task force

Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made remission an achievable goal for most patients. Reaching this target leads to improved outcomes. The objective was to develop recommendations for treating JIA to target. A Steering Committee formulated a set of recommendations based on evidence derived from a systematic literature review. These were subsequently discussed, amended and voted on by an international Task Force of 30 paediatric rheumatologists in a consensus-based, Delphi-like procedure. Although the literature review did not reveal trials that compared a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated development of recommendations. The group agreed on six overarching principles and eight recommendations. The main treatment target, which should be based on a shared decision with parents/patients, was defined as remission, with the alternative target of low disease activity. The frequency and timeline of follow-up evaluations to ensure achievement and maintenance of the target depend on JIA category and level of disease activity. Additional recommendations emphasise the importance of ensuring adequate growth and development and avoiding long-term systemic glucocorticoid administration to maintain the target. All items were agreed on by more than 80% of the members of the Task Force. A research agenda was formulated. The Task Force developed recommendations for treating JIA to target, being aware that the evidence is not strong and needs to be expanded by future research. These recommendations can inform various stakeholders about strategies to reach optimal outcomes for JIA.

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

Objective. 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. Methods. 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. Results. 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. Conclusion. 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.

Improving the Quality of Care in Children with Juvenile Idiopathic Arthritis: A Step in the Right Direction

Juvenile idiopathic arthritis (JIA) is heterogeneous in both its clinical presentation and etiology1,2. JIA can result in permanent physical disability due to joint damage, while additional morbidity can be related to its treatment and to effects on growth and development. Children with inadequately treated or recalcitrant JIA may have chronic pain, mood disturbances, and difficulty with peer relationships, school performance, and attainment of educational and vocational goals3,4,5,6,7,8. Improved health related quality of life (HRQOL) and physical function are increasingly recognized as key treatment goals because of the influence of this illness on all aspects of a child’s life9. Accurate evaluation of this multidimensional and heterogeneous disease is challenging, but crucial to improve the quality of care and outcomes in JIA. Over the last decade there has been an increasing commitment to the assessment and improvement of quality of care following the report of The Institute of Medicine (IOM) Committee on Quality of Healthcare in America, “To Err is Human”10. The American College of Rheumatology (ACR) and American Board of Pediatrics have charged … Address correspondence to Dr. Laxer. E-mail: ronald.laxer{at}sickkids.ca