To describe clinical outcomes of juvenile idiopathic arthritis (JIA) in a prospective inception cohort of children managed with contemporary treatments.
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.
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.
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.
Using Canadian Alliance of Pediatric Rheumatology Investigators (CAPRI) juvenile idiopathic arthritis (JIA) registry data, we describe (1) clinical characteristics of patients with JIA transitioning ...to adult care, (2) prevalence of disease-related damage and complications, and (3) changes in disease activity during the final year prior to transfer.
Registry participants who turned 17 years between February 2017 and November 2021 were included. Clinical characteristics and patient-reported outcomes (PROs) at the last recorded pediatric rheumatology visit, and changes observed in the year prior to that visit were analyzed. Physicians completed an additional questionnaire characterizing cumulative disease-related damage and adverse events by age 17 years.
At their last visit, 88 of 131 participants (67%) had inactive and 42 (32%) had active disease. Overall, 96 (73%) were on medications and 41 (31%) were on biologic disease-modifying antirheumatic drugs. Among 80 participants for whom the additional questionnaire was completed, 26% had clinically detected joint damage, 31% had joint damage on imaging, 14% had uveitis, and 7.5% had experienced at least 1 serious adverse event. During the final year, 44.2% of patients were in remission, 28.4% attained inactive disease, and 27.4% became or remained active. Mean scores of PROs were stable overall during that last year, but a minority reported marked worsening.
A substantial proportion of youth with JIA transitioning to adult care in Canada had a high disease burden, which was reflected by their degree of disease activity, joint damage, or ongoing medication use. These results will inform pediatric and adult providers of anticipated needs during transition of care.
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.
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.
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.
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 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.
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.
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.
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.
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.
Joint inflammation is the common feature underlying juvenile idiopathic arthritis (JIA). Clinicians recognize patterns of joint involvement currently not part of the International League of ...Associations for Rheumatology (ILAR) classification. Using unsupervised machine learning, we sought to uncover data-driven joint patterns that predict clinical phenotype and disease trajectories.
We analyzed prospectively collected clinical data, including joint involvement using a standard 71-joint homunculus, for 640 discovery patients with newly diagnosed JIA enrolled in a Canada-wide study who were followed serially for five years, treatment-naïve except for nonsteroidal anti-inflammatory drugs (NSAIDs) and diagnosed within one year of symptom onset. Twenty-one patients had systemic arthritis, 300 oligoarthritis, 125 rheumatoid factor (RF)-negative polyarthritis, 16 RF-positive polyarthritis, 37 psoriatic arthritis, 78 enthesitis-related arthritis (ERA), and 63 undifferentiated arthritis. At diagnosis, we observed global hierarchical groups of co-involved joints. To characterize these patterns, we developed sparse multilayer non-negative matrix factorization (NMF). Model selection by internal bi-cross-validation identified seven joint patterns at presentation, to which all 640 discovery patients were assigned: pelvic girdle (57 patients), fingers (25), wrists (114), toes (48), ankles (106), knees (283), and indistinct (7). Patterns were distinct from clinical subtypes (P < 0.001 by χ2 test) and reproducible through external data set validation on a 119-patient, prospectively collected independent validation cohort (reconstruction accuracy Q2 = 0.55 for patterns; 0.35 for groups). Some patients matched multiple patterns. To determine whether their disease outcomes differed, we further subdivided the 640 discovery patients into three subgroups by degree of localization-the percentage of their active joints aligning with their assigned pattern: localized (≥90%; 359 patients), partially localized (60%-90%; 124), or extended (<60%; 157). Localized patients more often maintained their baseline patterns (P < 0.05 for five groups by permutation test) than nonlocalized patients (P < 0.05 for three groups by permutation test) over a five-year follow-up period. We modelled time to zero joints in the discovery cohort using a multivariate Cox proportional hazards model considering joint pattern, degree of localization, and ILAR subtype. Despite receiving more intense treatment, 50% of nonlocalized patients had zero joints at one year compared to six months for localized patients. Overall, localized patients required less time to reach zero joints (partial: P = 0.0018 versus localized by log-rank test; extended: P = 0.0057). Potential limitations include the requirement for patients to be treatment naïve (except NSAIDs), which may skew the patient cohorts towards milder disease, and the validation cohort size precluded multivariate analyses of disease trajectories.
Multilayer NMF identified patterns of joint involvement that predicted disease trajectory in children with arthritis. Our hierarchical unsupervised approach identified a new clinical feature, degree of localization, which predicted outcomes in both cohorts. Detailed assessment of every joint is already part of every musculoskeletal exam for children with arthritis. Our study supports both the continued collection of detailed joint involvement and the inclusion of patterns and degrees of localization to stratify patients and inform treatment decisions. This will advance pediatric rheumatology from counting joints to realizing the potential of using data available from uncovering patterns of joint involvement.
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.
Abstract
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.
To (i) validate the JIA parent global assessment (parent global) as a health-related quality of life (HRQoL) instrument; (ii) evaluate measurement properties of accepted HRQoL measures relative to ...those of the parent global; and (iii) assess causal pathways determining parent global scores.
Data from the Research in Arthritis in Canadian Children emphasizing outcomes (ReACCh-Out) cohort were used. Measurement properties were assessed in 344 patients at enrolment and 6 months later. Causal pathways were tested by structural equation modelling to understand root causes and mediators leading to parent global scores.
Construct validity was supported by Spearman correlations of 0.53-0.70 for the parent global with the Juvenile Arthritis Quality of Life Questionnaire, Quality of My Life health scale (HRQoML), Pediatric Quality of Life Inventory (PedsQL)-Parent, and Child Health Questionnaire (CHQ)-Physical. Exceptions were PedsQL-Child (0.44) and CHQ-Psychosocial (0.31). Correlations were lower (0.14-0.49) with disease activity measures (physician global assessment of disease activity, active joint count, ESR). Responsiveness of the parent global to improvement according to parent ratings (0.51) was acceptable and within the range (0.32-0.71) of that of other measures. Reliability estimates and measurement errors for all measures were unsatisfactory, likely due to the prolonged time between assessments. Causal pathways for the parent global matched those previously reported for HRQoML.
Our results offer support for the parent global as a valid measure of HRQoL for JIA. If confirmed, existing studies using the parent global may be re-interpreted, enhancing our knowledge of HRQoL in children with JIA.
Abstract
Objective
Structural equation modelling was applied to data from the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort to help elucidate causal pathways to ...decreased health-related quality of life (HRQoL) in children with JIA.
Methods
Based on published literature and clinical plausibility, a priori models were constructed with explicit root causes (disease activity, treatment intensity) and mediators (pain, disease symptoms, functional impairments) leading to HRQoL measured by the Quality of my Life (QoML) scale and the Juvenile Arthritis Quality of Life Questionnaire (JAQQ) at five disease stages: (i) diagnosis, (ii) 3–9 months after diagnosis, (iii) flare, (iv) remission on medications, (v) remission off medications. Following structural equation modelling, a posteriori models were selected based on data fit and clinical plausibility.
Results
We included 561, 887, 137, 186 and 182 patients at each stage, respectively. In a posteriori models for active disease stages, paths from disease activity led through pain, functional impairments, and disease symptoms, directly or through restrictions in participation, to decreased QoML scores. Treatment intensity had detrimental effects through psychosocial domains; while treatment side effects had a lesser role. Pathways were similar for QoML and JAQQ, but JAQQ models provided greater specificity. Models for remission stages were not supported by the data.
Conclusion
Our findings support disease activity and treatment intensity as being root causes of decreased HRQoL in children with JIA, with pain, functional impairments, and participation restrictions being mediators for disease activity; they support psychosocial effects and side effects as being mediators for treatment intensity.