Search

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

Objective To identify differences between baseline Canadian JIA practices and the 2019 ACR guidelines for JIA. Methods Canadian paediatric rheumatologists were surveyed for their opinions on reasonable a priori target adherence rates for JIA guideline recommendations. Prospectively collected data for 266 newly diagnosed children from 2017 to 2019 were analysed to calculate observed adherence rates. Kaplan–Meier survival curves were used to estimate the cumulative incidence of starting synthetic or biologic DMARDs (sDMARD or bDMARD, respectively) for different patient groups. Results A total of 25/61 (41%) eligible physicians answered the survey. Most survey respondents (64%) felt that adherence targets should vary depending on the strength of the recommendation and quality of evidence, from a mean of 84% for strong recommendations with high-quality evidence to 29% for conditional recommendations with very low-quality evidence. Data showed 13/19 (68%) recommendations would have met proposed targets and 10/19 (53%) had ≥80% observed adherence. Exceptions were the use of subcutaneous vs oral MTX (53%) and infrequent treatment escalation from NSAIDs to bDMARDs in patients with sacroiliitis (31%) or enthesitis (0%). By 12 weeks, 95% of patients with polyarthritis received sDMARDs, 38% of patients with systemic JIA received bDMARDs and 22% of patients with sacroiliitis received bDMARDs. Conclusion Canadian paediatric rheumatology practices were in line with many 2019 JIA guideline recommendations before their publication, except for frequent use of oral MTX and infrequent direct escalation from NSAIDs to bDMARDs in sacroiliitis and enthesitis. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity.Methods: Plasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits.Results: At enrollment, sLRP1 levels correlated negatively with age and active joint counts. Children showed significantly higher levels of sLRP1 than adolescents (mean ranks: 55.4 and 41.9, respectively; P = 0.02). Participants with 4 or fewer active joints, compared to those with 5 or more active joints, had significantly higher sLRP1 levels (mean ranks: 56.2 and 40.7, respectively; P = 0.006). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r = -0.235, P = 0.017). In the entire cohort, sLRP1 levels at enrollment and 6 months later correlated with 13 and 6 pro- and antiinflammatory biomarkers, respectively. In JIA categories, sLRP1 correlations with inflammatory markers were significant in rheumatoid factor-negative polyarticular JIA, oligoarticular JIA, enthesitis-related arthritis, and psoriatic arthritis at enrollment. Higher sLRP1 levels at enrollment increased the likelihood of absence of active joints 6 months later.Conclusion: Plasma sLRP1 levels correlate with clinical and biomarker indicators of short-term improvement in JIA disease activity, supporting sLRP1 as an upstream biomarker of potential utility for assessing JIA disease activity and outcome prediction. [ABSTRACT FROM AUTHOR]

Objectives The aim was to describe the design, methods and initial findings of a new Canadian inception cohort of children with JIA, The Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) JIA Registry. Methods The CAPRI JIA Registry was started in 2017 to collect information prospectively on children enrolled within 3 months of JIA diagnosis across Canada. The registry has a non-traditional modular design, with no artificially set times for registry visits to occur, streamlined multi-method data collection that requires 2–4 min per visit, and reports cumulative incidence of treatments, outcomes and adverse events calculated by Kaplan–Meier survival methods. Results A total of 166 patients, enrolled a median of 6 weeks after JIA diagnosis at 10 centres, were included. The median age at diagnosis was 9 years [interquartile range (IQR) 3, 13], 61% were female and 51% had oligoarticular JIA. The median three-variable clinical Juvenile Arthritis Disease Activity Score was 6.5 (IQR 4, 10) at enrolment, and the median time to first attainment of clinically inactive disease (CID) was 24 weeks (by 1 year, 81%). Within 1 year of diagnosis, 70% of patients had started a DMARD and 35% a biologic agent. The rates of adverse events and serious adverse events were 60 and 5.8 per 100 patient-years, respectively. Conclusion This streamlined and flexible registry minimizes the burden of data collection and interference with clinic operations. Initial findings suggest that treatments for newly diagnosed patients with JIA in Canada have intensified, and now 81% of patients attain CID within 1 year of diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To estimate the impact of enthesitis on patient-reported outcomes in children with juvenile idiopathic arthritis (JIA), irrespective of JIA category.Methods: Children enrolled in the Research in Arthritis in Canadian Children Emphasizing Outcomes cohort were studied. Entheseal tenderness by physician examination in 33 defined locations, Juvenile Arthritis Quality of Life Questionnaire (JAQQ), Quality of My Life (QoML) Questionnaire, Childhood Health Assessment Questionnaire (C-HAQ), and a pain visual analog scale were completed at enrollment, every 6 months for 2 years, and then yearly up to 5 years. Analyses consisted of descriptive statistics, linear mixed models for longitudinal data, and analysis of covariance.Results: Among 1,371 patients followed for a median of 35.3 months (interquartile range 22.1, 49.2), 214 (16%) had enthesitis, of whom 137 (64%) were classified as having enthesitis-related arthritis. After adjusting for JIA category and covariates, children with enthesitis reported higher JAQQ (mean raw score 2.71 versus 2.16, adjusted difference 0.41 points; 95% confidence interval [95% CI] 0.22, 0.59), higher C-HAQ (0.47 versus 0.31, adjusted difference 0.14 points; 95% CI 0.07, 0.22), higher pain (3.01 versus 1.68, adjusted difference 0.94 points; 95% CI 0.64, 1.25), and lower QoML (7.02 versus 8.23, adjusted difference -0.80 points; 95% CI -1.09, -0.51) scores than children without enthesitis. These differences persisted up to 5 years.Conclusion: Children with enthesitis, regardless of JIA category, report worse patient-reported outcomes than those without enthesitis. Thus, enthesitis should be assessed in all children with JIA. [ABSTRACT FROM AUTHOR]

A number of studies have demonstrated that patients with autoimmune disease have lower levels of vitamin D prompting speculation that vitamin D might suppress inflammation and immune responses in children with juvenile idiopathic arthritis (JIA). The objective of this study was to compare vitamin D levels in children with JIA at disease onset with healthy children. We hypothesized that children and adolescents with JIA have lower vitamin D levels than healthy children and adolescents. Data from a Canadian cohort of children with new-onset JIA (n = 164, data collection 2007-2012) were compared to Canadian Health Measures Survey (CHMS) data (n =4027, data collection 2007-2011). We compared 25-hydroxy vitamin D (25(OH)D) concentrations with measures of inflammation, vitamin D supplement use, milk intake, and season of birth. Mean 25(OH)D level was significantly higher in patients with JIA (79 ± 3.1 nmol/L) than in healthy controls (68 ± 1.8 nmol/L P <.05). Patients with JIA more often used vitamin D containing supplements (50% vs. 7%; P <.05). The prevalence of 25(OH)D deficiency (<30 nmol/L) was 6% for both groups. Children with JIA with 25(OH)D deficiency or insufficiency (<50 nmol/L) had higher C-reactive protein levels. Children with JIA were more often born in the fall and winter compared to healthy children. In contrast to earlier studies, we found vitamin D levels in Canadian children with JIA were higher compared to healthy children and associated with more frequent use of vitamin D supplements. Among children with JIA, low vitamin D levels were associated with indicators of greater inflammation. [ABSTRACT FROM AUTHOR]

Objective: Our objectives were to quantify the relationships among fatigue, pain interference, and physical disability in children with juvenile idiopathic arthritis (JIA) and to test whether fatigue mediates the relationship between pain interference and physical disability in JIA., Methods: Patients enrolled within three months of JIA diagnosis in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry between February 2017 and May 2023 were included. Their parents completed the Patient-Reported Outcomes Measurement Information System fatigue and pain interference short proxy questionnaires and the Childhood Health Assessment Questionnaire disability index at registry enrollment. Associations were assessed using Pearson correlations and multiple linear regression. Structural equation modeling (SEM) was used to test if fatigue mediates the relationship between pain interference and physical disability., Results: Among 855 patients (61.4% female, 44.1% with oligoarthritis), most reported fatigue and pain interference scores similar to those in the reference population, but 15.6% reported severe fatigue and 7.3% reported severe pain interference, with wide variation across JIA categories. Fatigue was strongly correlated with pain interference (r = 0.72, P < 0.001) and with physical disability (r = 0.60, P < 0.001). Pain interference (β = 0.027, P < 0.001) and fatigue (β = 0.013, P < 0.001) were both associated with physical disability after controlling for each other and potential confounders. SEM supported our hypothesis that fatigue partially mediates the relationship between pain interference and physical disability., Conclusion: Our findings suggest both fatigue and pain interference are independently associated with physical disability in children newly diagnosed with JIA, and the effect of pain interference may be partly mediated by fatigue., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To develop Canadian recommendations for the screening, monitoring, and treatment of uveitis associated with juvenile idiopathic arthritis (JIA)., Methods: Recommendations were developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach. A working group of 14 pediatric rheumatologists, 6 ophthalmologists, 2 methodologists, and 3 caregiver/patient representatives reviewed recent American College of Rheumatology (ACR)/Arthritis Foundation (AF) recommendations and worked in pairs to develop evidence-to-decision (EtD) tables. A survey to assess agreement and recommendations requiring group discussion was completed. EtD tables were presented, discussed, and voted upon at a virtual meeting, to produce the final recommendations. A health equity framework was applied to all aspects of the adolopment process including the EtD tables, survey responses, and virtual meeting discussion., Results: The survey identified that 7 of the 19 recommendations required rigorous discussion. Seventy-five percent of working group members attended the virtual meeting to discuss controversial topics as they pertained to the Canadian environment, including timing to first eye exam, frequency of screening, escalation criteria for systemic and biologic therapy, and the role of nonbiologic therapies. Equity issues related to access to care and advanced therapeutics across Canadian provinces and territories were highlighted. Following the virtual meeting, 5 recommendations were adapted, 2 recommendations were removed, and 1 was developed de novo., Conclusion: Recommendations for JIA-associated uveitis were adapted to the Canadian context by a working group of pediatric rheumatologists, ophthalmologists with expertise in the management of uveitis, and parent/patient input, taking into consideration cost, equity, and access., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: The aim of this study was to develop and validate a brief disability screen for children with JIA, the Kids Disability Screen (KDS)., Methods: A total of 216 children enrolled in the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry in 2017-2018 formed a development cohort, and 220 children enrolled in 2019-2020 formed a validation cohort. At every clinic visit, parents answered two questions derived from the Childhood Health Assessment Questionnaire (CHAQ): 'Is it hard for your child to run and play BECAUSE OF ARTHRITIS?' ('Hard' 0-10), and 'Does your child usually need help from you or another person BECAUSE OF ARTHRITIS?' ('Help', 0-10). We used 36-fold cross-validation and tested nine different mathematical methods to combine the answers and optimize psychometric properties. The results were confirmed in the validation cohort., Results: Expressed as the mean of the two answers, KDS best balanced ease of use and psychometric properties, while a LASSO regression model combining the two answers with other patient characteristics [estimated CHAQ [eCHAQ]) had the highest responsiveness. In the validation cohort, 22.7%, 25.9% and 28.6% of patients had a score of 0 at enrolment for the KDS, eCHAQ and CHAQ, respectively. Responsiveness was 0.67, 0.74 and 0.62, respectively. Sensitivity to detect a CHAQ > 0 was 0.90 and specificity 0.56, KDS detecting some disability in 44% of children with a CHAQ = 0., Conclusion: This simple KDS has psychometric properties comparable with those of a full CHAQ and may be used at every clinic visit to identify those children who need a full disability assessment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To describe the frequency and severity of parent-reported medication side effects (SEs) in children with juvenile idiopathic arthritis (JIA) relative to physician-reported actionable adverse events (AEs), and to assess their impact on health-related quality of life (HRQoL)., Methods: Newly diagnosed JIA patients recruited between 2017 and 2019 to the Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) Registry were included. Parents reported presence and severity (0 = no problem, 10 = very severe) of medication SEs at every clinic visit. Physicians were asked to report any actionable AE. HRQoL was assessed using the Quality of My Life (QoML) questionnaire (0 = the worst, 10 = the best) and parent's global assessment (0 = very well, 10 = very poor). Analyses included proportion of visits with SEs or actionable AEs, cumulative incidence by Kaplan-Meier methods, and HRQoL impact measured with longitudinal mixed-effects models., Results: SEs were reported at 371 of 884 (42%) visits (95% confidence interval [95% CI] 39, 45%) in 249 patients, with a median of 2 SEs per visit (interquartile range [IQR] 1-3), and median severity of 3 (IQR 1.5-5). Most SEs were gastrointestinal (32.5% of visits) or behavioral/psychiatric (22.4%). SE frequency was lowest with nonsteroidal antiinflammatory drugs alone (34.7%) and highest with prednisone and methotrexate combinations (66%). SE cumulative incidence was 67% (95% CI 59, 75) within 1 year of diagnosis, and 36% (95% CI 28, 44) for actionable AEs. Parent global and QoML scores were worse with SEs present; the impact persisted after adjusting for pain and number of active joints., Conclusion: Parents report that two-thirds of children with JIA experience SEs impacting their HRQoL within 1 year of diagnosis. SE mitigation strategies are needed in managing JIA., (© 2021 American College of Rheumatology.)

Objective: To identify early predictors of disease activity at 18 months in JIA using clinical and biomarker profiling., Methods: Clinical and biomarker data were collected at JIA diagnosis in a prospective longitudinal inception cohort of 82 children with non-systemic JIA, and their ability to predict an active joint count of 0, a physician global assessment of disease activity of ≤1 cm, and inactive disease by Wallace 2004 criteria 18 months later was assessed. Correlation-based feature selection and ReliefF were used to shortlist predictors and random forest models were trained to predict outcomes., Results: From the original 112 features, 13 effectively predicted 18-month outcomes. They included age, number of active/effused joints, wrist, ankle and/or knee involvement, ESR, ANA positivity and plasma levels of five inflammatory biomarkers (IL-10, IL-17, IL-12p70, soluble low-density lipoprotein receptor-related protein 1 and vitamin D), at enrolment. The clinical plus biomarker panel predicted active joint count = 0, physician global assessment ≤ 1, and inactive disease after 18 months with 0.79, 0.80 and 0.83 accuracy and 0.84, 0.83, 0.88 area under the curve, respectively. Using clinical features alone resulted in 0.75, 0.72 and 0.80 accuracy, and area under the curve values of 0.81, 0.78 and 0.83, respectively., Conclusion: A panel of five plasma biomarkers combined with clinical features at the time of diagnosis more accurately predicted short-term disease activity in JIA than clinical characteristics alone. If validated in external cohorts, such a panel may guide more rationally conceived, biologically based, personalized treatment strategies in early JIA., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Undervaluing the effectiveness of conventional treatments may lead to overtreatment with biologic medications in children with juvenile idiopathic arthritis (JIA). Using data from a nationwide inception cohort and strict methods to control bias, the aim of our study was to estimate the real-world effectiveness of simple JIA treatment strategies recommended in current guidelines., Methods: Children with JIA who were recruited at 16 Canadian centers from 2005 to 2010 were followed for up to 5 years. For each child, all observed treatment changes over time were assessed by independent physicians using prospectively collected data and published response criteria. Success was defined as attainment of inactive disease or maintenance of this state when stepping down treatment; minimally active disease was deemed acceptable for children with polyarticular JIA. Success rates were calculated for treatments tried ≥25 times, and logistic regression analysis identified features associated with success., Results: A total of 4,429 treatment episodes were observed in 1,352 children. Nonsteroidal antiinflammatory drug (NSAID) monotherapy was attempted 697 times, mostly as initial treatment when <5 joints were involved, with a 54.4% success rate (95% confidence interval [95% CI] 50.3-58.6). NSAIDs plus joint injections had a 64.7% success rate (95% CI 59.8-69.7). Adding methotrexate to NSAIDs and/or joint injections (attempted 566 times) had a 60.5% success rate (95% CI 55.7-65.3). In adjusted analyses, each additional active joint reduced chances of success for treatment with NSAIDs (odds ratio [OR] 0.90 [95% CI 0.85-0.94]) and for methotrexate combinations (OR 0.96 [95% CI 0.94-0.99]). Each additional year after disease onset reduced chances of success for treatment with methotrexate combinations (OR 0.83 [95% CI 0.72-0.95])., Conclusion: These real-world effectiveness estimates show that conventional nonbiologic treatment strategies that are recommended in current guidelines are effective in achieving treatment targets in many children with JIA., (© 2019, American College of Rheumatology.)

Objective: To identify discrete clusters comprising clinical features and inflammatory biomarkers in children with JIA and to determine cluster alignment with JIA categories., Methods: A Canadian prospective inception cohort comprising 150 children with JIA was evaluated at baseline (visit 1) and after six months (visit 2). Data included clinical manifestations and inflammation-related biomarkers. Probabilistic principal component analysis identified sets of composite variables, or principal components, from 191 original variables. To discern new clinical-biomarker clusters (clusters), Gaussian mixture models were fit to the data. Newly-defined clusters and JIA categories were compared. Agreement between the two was assessed using Kruskal-Wallis analyses and contingency plots., Results: Three principal components recovered 35% (three clusters) and 40% (five clusters) of the variance in patient profiles in visits 1 and 2, respectively. None of the clusters aligned precisely with any of the seven JIA categories but rather spanned multiple categories. Results demonstrated that the newly defined clinical-biomarker lustres are more homogeneous than JIA categories., Conclusion: Applying unsupervised data mining to clinical and inflammatory biomarker data discerns discrete clusters that intersect multiple JIA categories. Results suggest that certain groups of patients within different JIA categories are more aligned pathobiologically than their separate clinical categorizations suggest. Applying data mining analyses to complex datasets can generate insights into JIA pathogenesis and could contribute to biologically based refinements in JIA classification., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Persistent systemic lupus erythematosus (SLE) disease activity is associated with increased morbidity and mortality. In a multicenter cohort of patients with prevalent SLE, we described persistence, patterns, and predictors of change in disease activity over time., Methods: Based on SLE Disease Activity Index (SLEDAI)-2K scores at cohort entry, patients were classified into 4 groups: low (score < 4; LOW), moderate (4 to < 6; MOD), moderately high (6 to ≤ 10; MHIGH), and very high (> 10; VHIGH). Multivariable linear and longitudinal mixed linear regression models were used to identify predictors of change over time in SLEDAI-2K., Results: There were 2019 participants, with declining followup data over 5 years (1326, 580, 274, 186, and 148 patients, respectively). At cohort entry, mean (± SD) age was 42 (± 17) years, disease duration 11 (± 10) years, and 90% were female. The 4 groups included 44% LOW (n = 891), 20% MOD (n = 400), 22% MHIGH (n = 442), and 14% VHIGH (n = 286); therefore, 36% had clinically important SLE activity. The proportion of patients in the LOW group at entry who moved to a higher activity level varied from 30% (167/557) at 1 year, to 49% (41/83) at 3 years, and 54% (30/56) at 5 years. Among 181 patients with MOD to VHIGH entry activity and 3 years of followup, 116 (64.1%) remained active. In all analyses, only higher SLEDAI-2K at cohort entry remained a significant predictor of higher SLEDAI-2K in subsequent years., Conclusion: Higher SLEDAI-2K at study entry was the single major independent predictor of higher SLEDAI-2K over time, reflecting frequent persistence of active disease, even in patients with longstanding disease. This highlights gaps in the optimal treatment of SLE.

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 Canadian varieties of English and French. The reading comprehension of the questionnaires were tested in a probe sample of ten parents and ten JIA patients for Canadian English and other ten parents and ten JIA patients for Canadian French. 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 3 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 208 JIA patients (2.9% systemic, 41.8% oligoarticular, 27.9% RF negative polyarthritis, 27.4% other categories) and 152 healthy children, were enrolled at two paediatric rheumatology centres. The JAMAR components discriminated well healthy subjects from JIA patients. Notably, there was no significant difference between the healthy subjects and their affected peers in the psychosocial quality of life variable. All JAMAR components revealed good psychometric performances. In conclusion, the Canadian English and French versions of the JAMAR are valid tools for the assessment of children with JIA and are suitable for use both in routine clinical practice and clinical research.

Objective: To describe changes in health-related quality of life (HRQoL) over time in children with juvenile idiopathic arthritis (JIA), relative to other outcomes, and to identify predictors of unfavorable HRQoL trajectories., Methods: Children with JIA in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort were included. The Juvenile Arthritis Quality of Life Questionnaire (JAQQ, a standardized instrument), health-related Quality of My Life (HRQoML, an instrument based on personal valuations), and JIA core variables were completed serially. Analyses included median values, Kaplan-Meier survival curves, and latent trajectory analysis., Results: A total of 1,249 patients enrolled at a median of 0.5 months after diagnosis were followed for a median of 34.2 months. The degree of initial HRQoL impairment and probabilities of reaching the best possible HRQoL scores varied across JIA categories (best for oligoarthritis, worst for rheumatoid factor-positive polyarthritis). Median times to attain best possible HRQoL scores (JAQQ 59.3 months, HRQoML 34.5 months), lagged behind those for disease activity, pain, and disability measures. Most patients followed trajectories with minimal or mild impairment; however, 7.6% and 13.8% of patients, respectively, followed JAQQ and HRQoML trajectories with persistent major impairment in HRQoL. JIA category, aboriginal ethnicity, and baseline disease activity measures distinguished between membership in trajectories with major and minimal impairments., Conclusion: Improvement in HRQoL is slower than for disease activity, pain, and disability. Improvement of a measure based on respondents' preferences (HRQoML) is more rapid than that of a standardized measure (JAQQ). Higher disease activity at diagnosis heralds an unfavorable HRQoL trajectory., (© 2017, American College of Rheumatology.)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To evaluate the influence of ethnicity on self-reported health-related quality of life (HRQOL) in the Canadian childhood-onset systemic lupus erythematosus (cSLE) population., Methods: Patients with cSLE at 4 pediatric centers were consecutively enrolled. Sociodemographics and multiple disease activity measures were collected. The Child Health Questionnaire (CHQ) was administered and analyzed by ethnicity., Results: We enrolled 213 cSLE patients, and complete data from 196 patients with the following ethnicities were analyzed: white (33%), Asian (32%), South Asian (16%), African American (11%), Latino/Hispanic (5%), and Aboriginal (4%). Compared to healthy children, cSLE patients rated their HRQOL significantly more poorly in 9 of 10 individual domains, and in 4 of 10 domains when compared to a cohort of juvenile arthritis patients. Within the cSLE cohort, CHQ scores were lower in 5 of 10 domains in white patients versus nonwhite ethnicities (P < 0.05 for each). Physical summary scores were lower for white patients compared to the other ethnicities aggregated together (mean ± SD 46.0 ± 11.9 versus 50.4 ± 10.1; P = 0.009); however, psychosocial summary scores were similar among the groups (mean ± SD 40.5 ± 14.6 versus 42.8 ± 12.7; P = 0.26). Disease activity measures, including the Systemic Lupus Erythematosus Disease Activity Index 2000, the Systemic Lupus Activity Measure, Revised, and physician global visual analog scale, were similar across ethnicities. However, patient-reported Systemic Lupus Erythematosus Activity Questionnaire symptom scores were greater in patients of white ethnicity compared to those of Asian ethnicity (mean ± SD 8.2 ± 5.8 versus 4.5 ± 4.7; P = 0.004)., Conclusion: The self- and parent-reported health status of Canadian cSLE patients differed across ethnicities, with white patients reporting lower HRQOL despite similar and overall low disease activity., (Copyright © 2014 by the American College of Rheumatology.)

Objective: To determine the influence of ethnicity and sociodemographic factors on disease characteristics of the Canadian pediatric lupus population., Methods: Childhood-onset systemic lupus erythematosus (SLE) patients at 4 pediatric centers in Halifax, Montreal, Toronto, and Vancouver were consecutively recruited. Sociodemographics and disease data were collected. Patients were categorized by their primary self-selected ethnicity, and exploratory cluster analyses were examined for disease expression by ethnicity., Results: We enrolled 213 childhood-onset SLE patients, and ethnicity data were available for 206 patients: white (31%), Asian (30%), South Asian (15%), black (10%), Latino/Hispanic (4%), Aboriginal (4%), and Arab/Middle Eastern (3%). The frequency of clinical classification criteria (malar rash, arthritis, serositis, and renal disease) and autoantibodies significantly differed among ethnicities. Medications were prescribed equally across ethnicities: 76% were taking prednisone, 86% antimalarials, and 56% required additional immunosuppressants. Cluster analysis partitioned into 3 main groups: mild (n = 50), moderate (n = 82), and severe (n = 68) disease clusters. Only 20% of white patients were in the severe cluster compared to 51% of Asian and 41% of black patients (P = 0.03). However, disease activity indices and damage scores were similar across ethnicities., Conclusion: Canadian childhood-onset SLE patients reflect our multiethnic population, with differences in disease manifestations, autoantibody profiles, and severity of disease expression by ethnicity., (Copyright © 2013 by the American College of Rheumatology.)

Objective: To compare access to biologic therapies for children with juvenile idiopathic arthritis (JIA) across Canada, and to identify differences in provincial regulations and criteria for access., Methods: Between June and August 2010, we compiled the provincial guidelines for reimbursement of biologic drugs for children with JIA and conducted a multicenter Canada-wide survey of pediatric rheumatologists to determine their experience with accessing biologic therapies for their patients., Results: There were significant difficulties accessing biologic treatments other than etanercept and abatacept for children. There were large discrepancies in the access criteria and coverage of biologic agents across provinces, notably with age restrictions for younger children., Conclusion: Canadian children with JIA may not receive optimal internationally recognized "standard" care because pediatric coverage for biologic drugs through provincial formularies is limited and inconsistent across the country. There is urgent need for public policy to improve access to biologic therapies for these children to ensure optimal short-term and longterm health outcomes.

Objective: To determine methotrexate (MTX) use and the degree to which Canadian pediatric rheumatologists adhere to the American College of Rheumatology (ACR) guidelines on monitoring for MTX toxicity., Methods: A 20-item questionnaire was e-mailed to 37 pediatric rheumatologists in 17 centers in Canada. A total of 28 (75.7%) responded., Results: The oral route (PO) of administration was preferred initially by 78.6% in most cases, but for more severe cases, this fell to 42.8%. Those who chose not to start PO used the subcutaneous route (SQ). When PO was initial treatment, a switch to SQ was undertaken because of dose escalation, lack of efficacy, or GI toxicity. An initial mean dose of 0.35-0.5 mg/kg/wk was prescribed by 51.8%. For 75%, the maximum dose was 1 mg/kg/wk (up to 25 mg). Complete blood count, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were determined by 100% at baseline and in followup; albumin and creatinine by 85.7% at baseline, but by only 71.4% and 67.8%, respectively, in followup. After a change in dose, 96.3% requested blood tests at least monthly; this was extended to every 6 to 8 weeks by 78.6% when the dose was stable. Side effects of recurrent nausea and/or vomiting were reported to occur frequently. No severe toxicity, and in particular no case of cirrhosis, was reported. Prophylactic folate supplementation was prescribed by almost all physicians., Conclusion: Most Canadian pediatric rheumatologists follow ACR guidelines to monitor for MTX toxicity in children with rheumatic diseases who were prescribed MTX. The variation in monitoring and response to toxicity raises the question whether specific pediatric guidelines should be developed.