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Infliximab and golimumab are intravenously (IV) administered tumor necrosis factor inhibitors approved to treat moderate-to-severe rheumatoid arthritis (RA) with concomitant methotrexate. Owing to differences in biologic construct, patients with IV-infliximab treatment failure may benefit from switching to IV-golimumab. Utilizing the ACR's Rheumatology Informatics System for Effectiveness (RISE), a large electronic health records registry based in the USA, we assessed RA disease activity in patients switching from IV-infliximab to IV-golimumab. This retrospective, longitudinal, single-arm study included adults (≥ 18 years) with ≥ 1 RA diagnosis code between 2014 and 2018 and ≥ 1 IV-infliximab prescription within 6 months of a new IV-golimumab order (index date). Longitudinal assessments of disease activity using the Clinical Disease Activity Index (CDAI) were calculated in patients continuing IV-golimumab for 6-9- and 9-12-months post-switch. Paired t-tests evaluated significance of mean improvements during the follow-up periods. Most RA patients with disease activity assessments during the 6-month follow-up (N = 100; mean age: 65.3 years; 81% female; 74% white) demonstrated moderate-to-high disease activity (CDAI: 73% [38/52]) at enrollment. On average, patients showed significant improvement in disease activity within 6-9 months of switching; mean CDAI scores improved from 21.3 to 14.1 (p

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. [ABSTRACT FROM AUTHOR]

Objective To describe 2-year trajectories of the clinical Juvenile Arthritis Disease Activity Score, 10 joints (cJADAS10) and associated baseline characteristics in patients with JIA. Methods JIA patients in the Childhood Arthritis and Rheumatology Research Alliance Registry enrolled within 3 months of diagnosis from 15 June 2015 to 6 December 2017 with at least two cJADAS10 scores and 24 months of follow-up were included. Latent growth curve models of cJADAS10 were analysed; a combination of Bayesian information criterion, posterior probabilities and clinical judgement was used to select model of best fit. Results Five trajectories were identified among the 746 included patients: High, Rapidly Decreasing (HRD) (n  = 199, 26.7%); High, Slowly Decreasing (HSD) (n  = 154, 20.6%); High, Increasing (HI) (n  = 39, 5.2%); Moderate, Persistent (MP) (n  = 218, 29.2%); and Moderate, Decreasing (MD) (n  = 136, 18.2%). Most patients spent a significant portion of time at moderate to high disease activity levels. At baseline, HSD patients were more likely to be older, have a lower physician global assessment, normal inflammatory markers, longer time to first biologic, and have taken systemic steroids compared with HRD. Those with a HI trajectory were more likely to be ANA negative, have a longer time to first biologic, and less likely to be taking a conventional synthetic DMARD compared with HRD. MP patients were more likely to be older with lower household income, longer time to diagnosis, and markers of higher disease activity than those with a MD trajectory. Conclusions Five trajectories of JIA disease activity, and associated baseline variables, were identified. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [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]

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 FROM AUTHOR]