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Objective: To describe high-dose biologic use when treating juvenile idiopathic arthritis (JIA)., Methods: Patients with JIA enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry and treated with a biologic after enrollment were eligible. We described the frequency of high-dose biologic use and characteristics of patients receiving high-dose biologics. We used regression modeling to compare 6-month outcomes (using disease activity measures) between those who increased their biologic from standard to high dose (high-dose group) to those who initiated and remained on standard dosing (no-change group), and to those who switched biologic agents (biologic-switch group). We also compared serious adverse events (SAEs) between groups., Results: A total of 5,352 patients with JIA were treated with biologics following enrollment; 1,080 (20%) had ever received a high-dose biologic. There were no significant differences in outcomes between the high-dose group and the biologic-switch group; both improved disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score 10 (-3.53 and -3.95, respectively; P = 0.68). Although the SAE rates in the high-dose group and the biologic-switch group were numerically higher than the no-change group, the event rates were similar, and neither rate was significantly higher than in the no-change group (unadjusted incident rate ratio 2.5 [95% confidence interval (95% CI) 0.7-8.5] and 1.8 [95% CI 0.7-4.6], respectively)., Conclusion: Dosing escalation appears to be a reasonable choice to improve disease control, but large, prospective, randomized studies evaluating specific biologic agents are needed., (© 2021 American College of Rheumatology.)

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 describe characteristics of children with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (PsA) who were enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry., Methods: All children with ERA and those with juvenile PsA were identified. Demographic characteristics, clinical characteristics, and treatments were described. The children with sacroiliitis and those without sacroiliitis were compared. In the children with sacroiliitis, the first visit with clinically active sacroiliitis (which came first in 72% of cases) was compared to the first visit without clinically active sacroiliitis., Results: A total of 902 children with ERA or juvenile PsA were identified. Children with ERA were older at diagnosis (ages 10.8 years versus 8.2 years; P < 0.01) and were more likely to be male (56% versus 38%; P < 0.01). Polyarticular involvement was reported in 57% of children with ERA and in 72% of those with juvenile PsA. Of the children tested, HLA-B27 was positive in 38% of those in the ERA group and in 12% of those in the juvenile PsA group. At least 1 biologic was taken by 72% of those with ERA and 64% of those with juvenile PsA. Sacroiliitis (diagnosed clinically and/or by imaging) was reported in 28% of the children (40% of those with ERA and 12% of those with juvenile PsA). Of these, 54% of the children were female, 36% were HLA-B27 positive, and 81% took at least 1 biologic. In children with sacroiliitis, scores according to the physician global assessment of disease activity, parent/patient global assessment of well-being, and clinical Juvenile Arthritis Disease Activity Score 10 were all significantly worse at the first visit with clinically active sacroiliitis versus the first visit without active sacroiliitis., Conclusion: In this registry, there are more than 900 children with ERA or juvenile PsA. There was high biologic use in this population, especially in those with sacroiliitis. Further, there was equal sex representation in those children with sacroiliitis., (© 2020, American College of Rheumatology.)

Objective: To operationalize and report on nationally endorsed rheumatoid arthritis (RA) performance measures (PMs) using health administrative data for British Columbia (BC), Canada., Methods: All patients with RA in BC ages ≥18 years were identified between January 1, 1997 and December 31, 2009 using health administrative data and followed until December 2014. PMs tested include: the percentage of incident patients with ≥1 rheumatologist visit within 365 days; the percentage of prevalent patients with ≥1 rheumatologist visit per year; the percentage of prevalent patients dispensed disease-modifying antirheumatic drug (DMARD) therapy; and time from RA diagnosis to DMARD therapy. Measures were reported on patients seen by rheumatologists, and in the total population., Results: The cohort included 38,673 incident and 57,922 prevalent RA cases. The percentage of patients seen by a rheumatologist within 365 days increased over time (35% in 2000 to 65% in 2009), while the percentage of RA patients under the care of a rheumatologist seen yearly declined (79% in 2001 to 39% in 2014). The decline was due to decreasing visit rates with increasing follow-up time rather than calendar effect. The percentage of RA patients dispensed a DMARD was suboptimal over follow-up (37% in 2014) in the total population but higher (87%) in those under current rheumatologist care. The median time to DMARD in those seen by a rheumatologist improved from 49 days in 2000 to 23 days in 2009, with 34% receiving treatment within the 14-day benchmark., Conclusion: This study describes the operationalization and reporting of national PMs using administrative data and identifies gaps in care to further examine and address., (© 2020, American College of Rheumatology.)

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 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., (© 2019, American College of Rheumatology.)

Objective: Identification of the incidence of juvenile idiopathic arthritis (JIA)-associated uveitis and its risk factors is essential to optimize early detection. Data from the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort were used to estimate the annual incidence of new-onset uveitis following JIA diagnosis and to identify associated risk factors., Methods: Data were reported every 6 months for 2 years, then yearly to 5 years. Incidence was determined by Kaplan-Meier estimators with time of JIA diagnosis as the reference point. Univariate log-rank analysis identified risk factors and Cox regression determined independent predictors., Results: In total, 1,183 patients who enrolled within 6 months of JIA diagnosis met inclusion criteria, median age at diagnosis of 9.0 years (interquartile range [IQR] 3.8-12.9), median follow-up of 35.2 months (IQR 22.7-48.3). Of these patients, 87 developed uveitis after enrollment. The incidence of new-onset uveitis was 2.8% per year (95% confidence interval [95% CI] 2.0-3.5) in the first 5 years. The annual incidence decreased during follow-up but remained at 2.1% (95% CI 0-4.5) in the fifth year, although confidence intervals overlapped. Uveitis was associated with young age (<7 years) at JIA diagnosis (hazard ratio [HR] 8.29, P < 0.001), positive antinuclear antibody (ANA) test (HR 3.20, P < 0.001), oligoarthritis (HR 2.45, P = 0.002), polyarthritis rheumatoid factor negative (HR 1.65, P = 0.002), and female sex (HR 1.80, P = 0.02). In multivariable analysis, only young age at JIA diagnosis and ANA positivity were independent predictors of uveitis., Conclusion: Vigilant uveitis screening should continue for at least 5 years after JIA diagnosis, and priority for screening should be placed on young age (<7 years) at JIA diagnosis and a positive ANA test., (© 2018, American College of Rheumatology.)

Objective: To estimate the incidence and prevalence of juvenile idiopathic arthritis (JIA) in children ages <16 years in the province of Manitoba, Canada, and to determine changes in estimates between 2000 and 2012., Methods: JIA cases were ascertained from the administrative health data of Manitoba, using a validated case-finding algorithm. Annual incidence and prevalence rates were estimated using a generalized linear model with generalized estimating equations (GEEs), adjusting for sociodemographic characteristics. Changes in estimates were tested using piecewise regression models., Results: A total of 455 cases of JIA prevalence met the inclusion criteria. Sex- and age-adjusted incidence estimates were 14.01 (95% confidence interval [95% CI] 13.52, 14.53) in 2000/2001 and 9.18 (95% CI 8.56, 9.85) in 2010/2011. Prevalence estimates were 65.33 (95% CI 63.87, 66.83) in 2000/2001 and 59.61 (95% CI 58.17, 61.08) in 2010/2011. A linear piecewise model provided the best fit to the data. There was a significant decrease in prevalence over the study period (-0.18 [95% CI -0.35, -0.02]; P = 0.0292) but no statistically significant change in incidence (-0.46 [95% CI -0.94, 0.01]; P = 0.0571). Sex-stratified models revealed a decrease for males in both prevalence (estimate -0.54 [95% CI -0.84, -10.25]; P = 0.0003) and incidence (estimate -1.02 [95% CI -2.02, -0.04]; P = 0.0439); there were no changes for females., Conclusion: Few population-based longitudinal epidemiologic studies of JIA have been conducted. Our findings suggested a decrease in overall JIA prevalence, and in incidence and prevalence in men. Further research to validate these findings in other cohorts and to explore factors that contribute to this change will benefit future health care planning for JIA., (© 2018, American College of Rheumatology.)

Objective: To describe the prevalence, associated characteristics, and course of enthesitis in a juvenile idiopathic arthritis (JIA) inception cohort., Methods: Canadian children newly diagnosed with JIA between 2005 and 2010 were categorized using International League of Associations for Rheumatology criteria at the 6-month visit and followed in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) cohort for up to 5 years. The presence of entheseal tenderness on examination at 33 sites shown on a homunculus was recorded at 0, 6, 12, 18, 24, 36, 48, and 60 months after enrollment. Enthesitis was defined as entheseal tenderness at more than 1 site or on more than 1 occasion. Analyses consisted of descriptive statistics and linear mixed models for longitudinal data., Results: Of 1,406 patients, 219 (16%) had enthesitis and, of those with enthesitis, 141 (64%) were classified as having enthesitis-related arthritis (ERA). Children with enthesitis were more often older (10.7 versus 7.5 years), male (57% versus 31%), and with polyarthritis (57% versus 41%) and sacroiliac involvement (30% versus 4%). Entheseal tenderness was most frequent at the calcaneal plantar fascial insertion (39%), Achilles tendon insertion (31%), and tibial tuberosity (30%). The mean number of tender entheseal sites decreased in parallel with active joint counts. There was no difference in active joint counts over time in children with or without enthesitis (P = 0.73)., Conclusion: Enthesitis was observed in 16% of patients with JIA, but only two thirds were categorized as having ERA. Contrary to expectations, most children with enthesitis had polyarticular involvement. The course of enthesitis paralleled the course of active joint counts., (© 2017, American College of Rheumatology.)

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 examine work absenteeism, job disruptions, and perceived productivity loss and factors associated with each outcome in young adults living with systemic lupus erythematosus (SLE) and juvenile arthritis (JA)., Methods: One hundred forty-three young adults, ages 18-30 years with SLE (54.5%) and JA (45.5%), completed an online survey of work experiences. Demographic, health (e.g., fatigue, disease activity), psychosocial (e.g., independence, social support), and work context (e.g., career satisfaction, job control, self-disclosure) information was collected. Participants were asked about absenteeism, job disruptions, and perceived productivity loss in the last 6 months. Log Poisson regression analyses examined factors associated with work outcomes., Results: A majority of participants (59%) were employed and reported a well-managed health condition. Employed respondents were satisfied with their career progress and indicated moderate job control. More than 40% of participants reported absenteeism, job disruptions, and productivity loss. Greater job control and self-disclosure, and less social support, were related to a higher likelihood of absenteeism. More disease activity was related to a greater likelihood of reporting job disruptions. Lower fatigue and higher job control were associated with a reduced likelihood of a productivity loss., Conclusion: Young adult respondents with rheumatic disease experienced challenges with employment, including absenteeism, job disruptions, and productivity loss. While related to greater absenteeism, job control could play a role in a young person's ability to manage their health condition and sustain productive employment. Greater attention should also be paid to understanding health factors and social support in early work experiences., (© 2015, American College of Rheumatology.)

Objective: To examine the temporal and dose-related effects of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases., Methods: Children initiating GCs for a rheumatic disease (n = 130) were assessed every 3 months for 18 months. BMI, weight, and height Z score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (<0.2 mg/kg/day to a maximum of 7.5 mg/day), and moderate (between high and low) dosage. The impact of GC dosing, underlying diagnosis, pubertal status, physical activity, and disease activity on BMI Z scores and on percent body fat was assessed with longitudinal mixed-effects growth curve models., Results: The GC starting dose was high in 59% and moderate in 39% of patients. The peak BMI Z score was +1.29 at 4 months with high-dose GCs and +0.69 at 4.2 months with moderate-dose GCs (P < 0.001). Overall, 50% (95% confidence interval 41-59%) of the children returned to within +0.25 SD of their baseline BMI Z score. Oral GC dose over the preceding 3 months was the most significant determinant of BMI Z score and percent body fat. The proportion of days in receipt of GCs, disease activity, and a diagnosis of systemic-onset juvenile idiopathic arthritis were also associated with BMI Z scores. The correlation between changes in BMI and changes in percent body fat was 0.09., Conclusion: In children with rheumatic diseases starting moderate and high doses of GCs, BMI Z scores peaked at 4 months, and only half returned to within +0.25 SD of their baseline BMI Z score after 18 months., (Copyright © 2013 by the American College of Rheumatology.)