EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update.

OBJECTIVE: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. METHODS: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. RESULTS: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. CONCLUSION: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

Is time a healer? How quality of life changes over time reported by parents of children and young people with juvenile idiopathic arthritis.

OBJECTIVE: To investigate changes in health-related quality of life (HRQoL) in children and young people with JIA (Juvenile Idiopathic Arthritis) over 3 years following diagnosis. METHODS: Data on children and young people recruited to the Childhood Arthritis Prospective Study (CAPS) were selected if >5 years of age at diagnosis. HRQoL was assessed at diagnosis (baseline), 1 year and 3 years using the proxy-reported Child Health Questionnaire (CHQ) completed by a parent or guardian. The CHQ measures aspects of HRQoL including physical functioning and mental health. Analyses included descriptive statistics, comparison with a US reference population and analysis of CHQ scores longitudinally and by gender and age of onset. RESULTS: Using CHQ data from parents/guardians of 182 CAPS study participants [median age 9.6 years (interquartile range 7.2-12.2)], all HRQoL domains significantly improved over the 3 year follow-up, except general health perceptions. Physical health domains showed greater improvement than psychosocial domains, although psychosocial scores were generally higher than physical scores throughout. Although similar at diagnosis, at 1 year females had significantly worse HRQoL than males in physical functioning (P = 0.03), bodily pain (P = 0.03), mental health (P = 0.00), social-emotional (P = 0.02) and social-physical (P < 0.001). Differences largely remained at 3 years. Age at onset was not significantly associated with HRQoL. CONCLUSION: Children and young people with JIA have low HRQoL across domains compared with the reference population. This improves within 3 years of diagnosis, with the greatest improvement within the first year. Early developmentally appropriate clinical intervention is recommended to reduce both psychosocial and physical impact of JIA. The lower HRQoL scores of females require further investigation.

No evidence that genetic predictors of susceptibility predict changes in core outcomes in JIA.

OBJECTIVES: The clinical progression of JIA is unpredictable. Knowing who will develop severe disease could facilitate rapid intensification of therapies. We use genetic variants conferring susceptibility to JIA to predict disease outcome measures. METHODS: A total of 713 JIA patients with genotype data and core outcome variables (COVs) at diagnosis (baseline) and 1 year follow-up were identified from the Childhood Arthritis Prospective Study (CAPS). A weighted genetic risk score (GRS) was generated, including all single nucleotide polymorphisms (SNPs) previously associated with JIA susceptibility (P-value < 5×10-08). We used multivariable linear regression to test the GRS for association with COVS (limited joint count, active joint count, physician global assessment, parent/patient general evaluation, childhood HAQ and ESR) at baseline and change in COVS from baseline to 1 year, adjusting for baseline COV and International League of Associations of Rheumatology (ILAR) category. The GRS was split into quintiles to identify high (quintile 5) and low (quintile 1) risk groups. RESULTS: Patients in the high-risk group for the GRS had a younger age at presentation (median low risk 7.79, median high risk 3.51). No association was observed between the GRS and any outcome measures at 1 year follow-up or baseline. CONCLUSION: For the first time we have used all known JIA genetic susceptibility loci (P=<5×10-08) in a GRS to predict changes in disease outcome measured over time. Genetic susceptibility variants are poor predictors of changes in core outcome measures, it is likely that genetic factors predicting disease outcome are independent to those predicting susceptibility. The next step will be to conduct a genome-wide association analysis of JIA outcome.

Public understanding of female genital anatomy and pelvic organ prolapse (POP); a questionnaire-based pilot study.

INTRODUCTION AND HYPOTHESIS: Health literacy underpins informed consent and shared decision-making. In gynaecology, this includes understanding of normal anatomy and urogenital disease. This study evaluated public knowledge of external female genital anatomy and pelvic organ prolapse (POP). METHODS: A questionnaire study asked participants for their demographics and to label a female external genitalia diagram and included free-text questions on POP, its symptoms and treatment. Questionnaires were distributed at general outpatient (OPD) and urogynaecology (UG) departments at a UK teaching hospital. Differences in the number of correct anatomy labels between participant genders were assessed via chi-squared tests and, within female participants, multivariable linear and logistic regressions assessed associations with increasing correct anatomical labels and an understanding (versus no understanding) of POP, respectively. RESULTS: Within 191 (n = 160 OPD, n = 31 UG), 9/103 (9%) labelled all anatomical structures correctly. Females had more correct labels (median 1, IQR 0,3) versus males (median 0, IQR 0,1), P = 0.022). Higher education (vs. < secondary) and white ethnicity were associated with greater numbers of correct labels [coefficient (95% CI): 1.05 (0.14, 1.96), P = 0.024, 1.45 (0.58, 2.33), P = 0.001 respectively]. Fifty-three per cent understood POP. POP understanding increased with increasing age, white ethnicity (OR: 4.38, 95% CI: 1.36, 14.08, P = 0.013) and more correct anatomy labels (OR: 1.43, 95% CI 1.14, 1.79, P = 0.002). Of those who understood POP, only 35% identified "bulge" as a symptom and 7% physiotherapy as a treatment option. CONCLUSION: There was poor public understanding of external female genital anatomy and POP, which may have significant implications for health-seeking, shared decision-making and informed consent.

Mortality related to general anaesthesia and sedation in dogs under UK primary veterinary care.

OBJECTIVES: To quantify and explore risk factors in dogs seen at primary care UK veterinary clinics for general anaesthetic (GA)/sedative-related death overall, in addition to neuter-specific procedures. STUDY DESIGN: A nested case-control study within UK primary care veterinary electronic patient record surveillance programme, VetCompass, including over 300 UK veterinary practices. ANIMALS: A total of 157,318 dogs undergoing GA/sedative events. METHODS: Cases included dogs undergoing GA/sedative events between January 2010 and December 2013 with GA/sedative-related death recorded within 48 hours or 2 weeks of the event. Controls were randomly selected from dogs undergoing GA/sedation that did not die within these time periods. Risks of GA/sedative-related death for all surgeries and neuter-specific surgeries were estimated. Demographic and clinical associations with GA/sedative-related death were reported as odds ratios following multivariable logistic regression modelling. Statistical significance was set at 5%. RESULTS: From 157,318 dogs with a GA/sedative event, there were 159 (0.10%) within 48 hours and 219 (0.14%) GA/sedative-related deaths within 2 weeks. Within 89,852 dogs that underwent a neuter surgery, there were eight GA/sedative related (0.009%). Greater age, poorer American Society of Anaesthesiologists health status scores and more urgent procedures were associated with greater odds of death. Compared with mixed breeds, Rottweilers and West Highland White Terriers had greater odds and Cocker Spaniels had lower odds of GA/sedative-related death. CONCLUSIONS AND CLINICAL RELEVANCE: The overall risk for GA/sedative related death was relatively low, particularly among the subset of dogs undergoing castration or ovariohysterectomy surgery. Associations and risk estimates may assist shared decision-making in clinical practice and provide benchmarks for audit.

Nothing about us without us: involving patient collaborators for machine learning applications in rheumatology.

Novel machine learning methods open the door to advances in rheumatology through application to complex, high-dimensional data, otherwise difficult to analyse. Results from such efforts could provide better classification of disease, decision support for therapy selection, and automated interpretation of clinical images. Nevertheless, such data-driven approaches could potentially model noise, or miss true clinical phenomena. One proposed solution to ensure clinically meaningful machine learning models is to involve primary stakeholders in their development and interpretation. Including patient and health care professionals' input and priorities, in combination with statistical fit measures, allows for any resulting models to be well fit, meaningful, and fit for practice in the wider rheumatological community. Here we describe outputs from workshops that involved healthcare professionals, and young people from the Your Rheum Young Person's Advisory Group, in the development of complex machine learning models. These were developed to better describe trajectory of early juvenile idiopathic arthritis disease, as part of the CLUSTER consortium. We further provide key instructions for reproducibility of this process.Involving people living with, and managing, a disease investigated using machine learning techniques, is feasible, impactful and empowering for all those involved.

Risk factors associated with albuminuria in Rwanda: results from a STEPS survey.

BACKGROUND: Non-communicable diseases (NCDs) are a growing burden which affects every part of the world, including developing countries. Chronic kidney disease (CKD) has varied etiology which can result from or complicate other NCDs such as diabetes and cardiovascular diseases. The growing prevalence of NCDs coupled with the increasing age in most developing countries, has seen a marked increase of CKD in these settings. CKD has been described as "the most neglected NCD" and greatly affects the quality of life of patients. It also places a huge economic burden on societies. However, few epidemiological data exist, particularly in sub-Saharan Africa. Assessment of the prevalence of albuminuria as a marker of kidney damage and CKD progression and its main risk factors was thus needed in Rwanda. METHODS: This study analyzed data collected during the first STEPwise approach to NCD risk factor Surveillance (STEPS) survey in Rwanda, conducted from 2012 to 2013, to assess the prevalence of albuminuria. A multistage cluster sampling allowed to select a representative sample of the general population. Furthermore, descriptive, as well as univariable analyses and multiple logistic regression were performed to respond to the research question. RESULTS: This survey brought a representative sample of 6,998 participants, among which 4,384 (62.65%) were female. Median age was 33 years (interquartile range, IQR 26-44), and over three quarters (78.45%) lived in rural areas. The albuminuria prevalence was 105.9 per 1,000 population. Overall, semi-urban and urban residency were associated with lower odds of CKD (odds ratio, OR 0.36, CI 0.23-0.56, p<0.001 and OR 0.34, CI 0.23-0.50, p<0.001, respectively) than rural status. Being married or living with a partner had higher odds (OR 1.44 (CI 1.03-2.02, p=0.031) and OR 1.62 (CI 1.06-2.48, p=0.026), respectively) of CKD than being single. Odds of positive albuminuria were also greater among participants living with human immunodeficiency virus (HIV) (OR 1.64, CI 1.09- 2.47, p=0.018). Gender, age group, smoking status and vegetable consumption, body mass index (BMI) and hypertension were not associated with albuminuria. CONCLUSION: The albuminuria prevalence was estimated at 105.9 per 1,000 in Rwanda. Rural residence, partnered status and HIV positivity were identified as main risk factors for albuminuria. Increased early screening of albuminuria to prevent CKD among high-risk groups, especially HIV patients, is therefore recommended.

CAPTURE-JIA: a consensus-derived core dataset to improve clinical care for children and young people with juvenile idiopathic arthritis.

OBJECTIVES: Data collected during routine clinic visits are key to driving successful quality improvement in clinical services and enabling integration of research into routine care. The purpose of this study was to develop a standardized core dataset for juvenile idiopathic arthritis (JIA) (termed CAPTURE-JIA), enabling routine clinical collection of research-quality patient data useful to all relevant stakeholder groups (clinicians, service-providers, researchers, health service planners and patients/families) and including outcomes of relevance to patients/families. METHODS: Collaborative consensus-based approaches (including Delphi and World Café methodologies) were employed. The study was divided into discrete phases, including collaborative working with other groups developing relevant core datasets and a two-stage Delphi process, with the aim of rationalizing the initially long data item list to a clinically feasible size. RESULTS: The initial stage of the process identified collection of 297 discrete data items by one or more of fifteen NHS paediatric rheumatology centres. Following the two-stage Delphi process, culminating in a consensus workshop (May 2015), the final approved CAPTURE-JIA dataset consists of 62 discrete and defined clinical data items including novel JIA-specific patient-reported outcome and experience measures. CONCLUSIONS: CAPTURE-JIA is the first 'JIA core dataset' to include data items considered essential by key stakeholder groups engaged with leading and improving the clinical care of children and young people with JIA. Collecting essential patient information in a standard way is a major step towards improving the quality and consistency of clinical services, facilitating collaborative and effective working, benchmarking clinical services against quality indicators and aligning treatment strategies and clinical research opportunities.

"Asking Too Much?": Randomized N-of-1 Trial Exploring Patient Preferences and Measurement Reactivity to Frequent Use of Remote Multidimensional Pain Assessments in Children and Young People With Juvenile Idiopathic Arthritis.

BACKGROUND: Remote monitoring of pain using multidimensional mobile health (mHealth) assessment tools is increasingly being adopted in research and care. This assessment method is valuable because it is challenging to capture pain histories, particularly in children and young people in diseases where pain patterns can be complex, such as juvenile idiopathic arthritis (JIA). With the growth of mHealth measures and more frequent assessment, it is important to explore patient preferences for the timing and frequency of administration of such tools and consider whether certain administrative patterns can directly impact on children's pain experiences. OBJECTIVE: This study aimed to explore the feasibility and influence (in terms of objective and subjective measurement reactivity) of several time sampling strategies in remote multidimensional pain reporting. METHODS: An N-of-1 trial was conducted in a subset of children and young people with JIA and their parents recruited to a UK cohort study. Children were allocated to 1 of 4 groups. Each group followed a different schedule of completion of MPT for 8 consecutive weeks. Each schedule included 2 blocks, each comprising 4 different randomized time sampling strategies, with each strategy occurring once within each 4-week block. Children completed MPT according to time sampling strategies: once-a-day, twice-a-day, once-a-week, and as-and-when pain was experienced. Adherence to each strategy was calculated. Participants completed the Patient-Reported Outcomes Measurement Information System Pain Interference Scale at the end of each week to explore objective reactivity. Differences in pain interference scores between time sampling strategies were assessed graphically and using Friedman tests. Children and young people and their parents took part in a semistructured interview about their preferences for different time sampling strategies and to explore subjective reactivity. RESULTS: A total of 14 children and young people (aged 7-16 years) and their parents participated. Adherence to pain reporting was higher in less intense time sampling strategies (once-a-week=63% [15/24]) compared with more intense time sampling strategies (twice-a-day=37.8% [127/336]). There were no statistically significant differences in pain interference scores between sampling strategies. Qualitative findings from interviews suggested that children preferred once-a-day (6/14, 43%) and as-and-when pain reporting (6/14, 43%). Creating routine was one of the most important factors for successful reporting, while still ensuring that comprehensive information about recent pain was captured. CONCLUSIONS: Once-a-day pain reporting provides rich contextual information. Although patients were less adherent to this preferred sampling strategy, once-a-day reporting still provides more frequent assessment opportunities compared with other less intense or overburdensome schedules. Important issues for the design of studies and care incorporating momentary assessment techniques were identified. We demonstrate that patient reporting preferences are key to accommodate and are important where data capture quality is key. Our findings support frequent administration of such tools, using daily reporting methods where possible.

How common is clinically inactive disease in a prospective cohort of patients with juvenile idiopathic arthritis? The importance of definition.

OBJECTIVES: Many criteria for clinically inactive disease (CID) and minimal disease activity (MDA) have been proposed for juvenile idiopathic arthritis (JIA). It is not known to what degree each of these criteria overlap within a single patient cohort. This study aimed to compare the frequency of MDA and CID across different criteria in a cohort of children with JIA at 1 year following presentation. METHODS: The Childhood Arthritis Prospective Study recruits children at initial presentation to paediatric or adolescent rheumatology in seven UK centres. Children recruited between October 2001 and December 2013 were included. The proportions of children with CID and MDA at 1 year were calculated using four investigator-defined and eight published composite criteria. Missing data were accounted for using multiple imputation under different assumptions. RESULTS: In a cohort of 1415 children and adolescents, 67% patients had no active joints at 1 year. Between 48% and 61% achieved MDA and between 25% and 38% achieved CID using published criteria. Overlap between criteria varied. Of 922 patients in MDA by either the original composite criteria, Juvenile Arthritis Disease Activity Score (JADAS) or clinical JADAS cut-offs, 68% were classified as in MDA by all 3 criteria. Similarly, 44% of 633 children with CID defined by either Wallace's preliminary criteria or the JADAS cut-off were in CID according to both criteria. CONCLUSIONS: In a large JIA prospective inception cohort, a majority of patients have evidence of persistent disease activity after 1 year. Published criteria to capture MDA and CID do not always identify the same groups of patients. This has significant implications when defining and applying treat-to-target strategies.

Towards stratified treatment of JIA: machine learning identifies subtypes in response to methotrexate from four UK cohorts.

BACKGROUND: Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures. METHODS: Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year. Clusters of MTX 'response' were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment. FINDINGS: The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65-0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns. INTERPRETATION: Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis of a stratified medicine programme in early JIA. FUNDING: Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and the National Institute for Health Research.

Overlap of International League of Associations for Rheumatology and Preliminary Pediatric Rheumatology International Trials Organization Classification Criteria for Nonsystemic Juvenile Idiopathic Arthritis in an Established UK Multicentre Inception Cohort.

OBJECTIVE: The goal was to assess the degree of overlap between existing International League of Associations for Rheumatology (ILAR) and preliminary Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria for juvenile idiopathic arthritis (JIA). METHODS: Participants from the Childhood Arthritis Prospective Study, a multicenter UK JIA inception cohort, were classified using the PRINTO and ILAR classification criteria into distinct categories. Systemic JIA was excluded because several classification items were not collected in this cohort. Adaptations to PRINTO criteria were required to apply to a UK health care setting, including limiting the number of blood biomarker tests required. The overlap between categories under the two systems was determined, and any differences in characteristics between groups were described. RESULTS: A total of 1,223 children and young people with a physician's diagnosis of JIA were included. Using PRINTO criteria, the majority of the patients had "other JIA" (69.5%). There was a high degree of overlap (91%) between the PRINTO enthesitis/spondylitis- and ILAR enthesitis-related JIA categories. The PRINTO rheumatoid factor (RF)-positive category was composed of 48% ILAR RF-positive polyarthritis and 52% undifferentiated JIA. The early-onset antinuclear antibodies-positive PRINTO category was largely composed of ILAR oligoarthritis (50%), RF-negative polyarthritis (24%), and undifferentiated JIA (23%). A few patients were unclassified under PRINTO (n = 3) and would previously have been classified as enthesitis-related JIA (n = 1) and undifferentiated JIA (n = 2) under ILAR. CONCLUSION: Under the preliminary PRINTO classification criteria for childhood arthritis, most children are not yet classified into a named category. These data can help support further delineation of the PRINTO criteria to ensure homogenous groups of children can be identified.

COVID-19-related anxiety trajectories in children, young people and adults with rheumatic diseases.

Objectives: Uncertainty regarding the risk of coronavirus disease 2019 (COVID-19), its complications and the safety of immunosuppressive therapies may drive anxiety among adults and parents of children and young people (CYP) with rheumatic diseases. This study explored trajectories of COVID-related anxiety in adults and parents of CYP with rheumatic diseases. Methods: Adults and parents of CYP participating in the international COVID-19 European Patient Registry were included in the current study if they had enrolled in the 4 weeks following 24 March 2020. COVID-related anxiety scores (0-10) were collected weekly for up to 28 weeks.Group-based trajectory models explored COVID-related anxiety clusters in adult and parent populations, with optimal models chosen based on model fit, parsimony and clinical plausibility. Demographic, clinical and COVID-19 mitigation behaviours were compared between identified clusters using univariable statistics. Results: In 498 parents of CYP and 2640 adults, four common trajectory groups of COVID-related anxiety were identified in each cohort: persistent extreme anxiety (32% and 17%), persistent high anxiety (43% and 41%), improving high anxiety (25% and 32%) and improving moderate anxiety (11% and 10%), respectively. Few characteristics distinguished the clusters in the parent cohort. Higher and more persistent anxiety clusters in the adult cohort were associated with higher levels of respiratory comorbidities, use of immunosuppressive therapies, older age and greater self-isolation. Conclusions: COVID-19-related anxiety in the rheumatic disease community was high and persistent during the COVID-19 pandemic, with four common patterns identified. In the adult cohort, higher COVID-related anxiety was related to perceived risk factors for COVID-19 morbidity and mortality.

The successes and challenges of harmonising juvenile idiopathic arthritis (JIA) datasets to create a large-scale JIA data resource.

BACKGROUND: CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges and progress towards creation of this unique large JIA dataset. METHODS: Four real-world studies contributed data; two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi) were created. Variables were selected based on a previously developed core dataset, and encrypted NHS numbers were used to identify children contributing similar data across multiple studies. RESULTS: Of 7013 records (from 5435 individuals), 2882 (1304 individuals) represented the same child across studies. The final datasets contain 2899 (MTX) and 2401 (TNFi) unique patients; 1018 are in both datasets. Missingness ranged from 10 to 60% and was not improved through harmonisation. CONCLUSIONS: Combining data across studies has achieved dataset sizes rarely seen in JIA, invaluable to progressing research. Losing variable specificity and missingness, and their impact on future analyses requires further consideration.

The Role of Age in Delays to Rheumatological Care in Juvenile Idiopathic Arthritis.

OBJECTIVE: To investigate the relationship between age and symptom duration at initial presentation to pediatric rheumatology for juvenile idiopathic arthritis (JIA). METHODS: In children and young people (CYP) enrolled in the Childhood Arthritis Prospective Study prior to March 2018, an association between age at presentation (< 5, 5-11, and > 11 yrs) and symptom duration was tested by multivariable linear regression. RESULTS: In 1577 CYP, 5- to 11-year-olds took 3.2 months longer and > 11-year-olds 6.9 months longer to reach pediatric rheumatology than < 5-year-olds. CONCLUSION: Adolescents take longer to reach pediatric rheumatology, potentially affecting their longer-term outcomes given the window of opportunity for JIA treatment.

Patient-reported wellbeing and clinical disease measures over time captured by multivariate trajectories of disease activity in individuals with juvenile idiopathic arthritis in the UK: a multicentre prospective longitudinal study.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease, the signs and symptoms of which can be summarised with use of composite disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score (cJADAS). However, clusters of children and young people might experience different global patterns in their signs and symptoms of disease, which might run in parallel or diverge over time. We aimed to identify such clusters in the 3 years after a diagnosis of JIA. The identification of these clusters would allow for a greater understanding of disease progression in JIA, including how physician-reported and patient-reported outcomes relate to each other over the JIA disease course. METHODS: In this multicentre prospective longitudinal study, we included children and young people recruited before Jan 1, 2015, to the Childhood Arthritis Prospective Study (CAPS), a UK multicentre inception cohort. Participants without a cJADAS score were excluded. To assess groups of children and young people with similar disease patterns in active joint count, physician's global assessment, and patient or parental global evaluation, we used latent profile analysis at initial presentation to paediatric rheumatology and multivariate group-based trajectory models for the following 3 years. Optimal models were selected on the basis of a combination of model fit, clinical plausibility, and model parsimony. FINDING: Between Jan 1, 2001, and Dec 31, 2014, 1423 children and young people with JIA were recruited to CAPS, 239 of whom were excluded, resulting in a final study population of 1184 children and young people. We identified five clusters at baseline and six trajectory groups using longitudinal follow-up data. Disease course was not well predicted from clusters at baseline; however, in both cross-sectional and longitudinal analyses, substantial proportions of children and young people had high patient or parent global scores despite low or improving joint counts and physician global scores. Participants in these groups were older, and a higher proportion of them had enthesitis-related JIA and lower socioeconomic status, compared with those in other groups. INTERPRETATION: Almost one in four children and young people with JIA in our study reported persistent, high patient or parent global scores despite having low or improving active joint counts and physician's global scores. Distinct patient subgroups defined by disease manifestation or trajectories of progression could help to better personalise health-care services and treatment plans for individuals with JIA. FUNDING: Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children's Charity, Olivia's Vision, and National Institute for Health Research.

Common Functional Ability Score for Young People With Juvenile Idiopathic Arthritis.

OBJECTIVE: As young people enter adulthood, the interchangeable use of child and adult outcome measures may inaccurately capture changes over time. This study aimed to use item response theory (IRT) to model a continuous score for functional ability that can be used no matter which questionnaire is completed. METHODS: Adolescents (ages 11-17 years) in the UK Childhood Arthritis Prospective Study (CAPS) self-completed an adolescent Childhood Health Assessment Questionnaire (CHAQ) and a Health Assessment Questionnaire (HAQ). Their parents answered the proxy-completed CHAQ. Those children with at least 2 simultaneously completed questionnaires at initial presentation or 1 year were included. Psychometric properties of item responses within each questionnaire were tested using Mokken analyses to assess the applicability of IRT modeling. A previously developed IRT model from the Pharmachild-NL registry from The Netherlands was validated in CAPS participants. Agreement and correlations between IRT-scaled functional ability scores were tested using intraclass correlations and Wilcoxon's signed rank tests. RESULTS: In 303 adolescents, the median age at diagnosis was 13 years, and 61% were female. CHAQ scores consistently exceeded HAQ scores. Mokken analyses demonstrated high scalability, monotonicity, and the fact that each questionnaire yielded reliable scores. There was little difference in item response characteristics between adolescents enrolled in CAPS and Pharmachild-NL (maximum item residual 0.08). Significant differences were no longer evident between IRT-scaled HAQ and CHAQ scores. CONCLUSION: IRT modeling allows the direct comparison of function scores regardless of different questionnaires being completed by different people over time. IRT modeling facilitates the ongoing assessment of function as adolescents transfer from pediatric clinics to adult services.

Validation of novel patient-centred juvenile idiopathic arthritis-specific patient-reported outcome and experience measures (PROMs/PREMs).

BACKGROUND: Measuring the outcomes that matter to children and young people (CYP) with juvenile idiopathic arthritis (JIA), is a necessary precursor to patient-centred improvements in quality of clinical care. We present a two-centre validation of novel JIA patient-reported outcome and experience measures (PROM and PREM) developed as part of the CAPTURE-JIA project. METHODS: CYP with JIA were recruited from paediatric rheumatology clinics, completing the CAPTURE-JIA PROM and PREM, CHAQ and CHU 9D. A subset participated in face-to-face interviews and completed the PROM/PREM 1 week later. The OMERACT filter was applied and the three domains of validation assessed. Truth assessments included cognitive interviewing, sensitivity analysis and Spearman's correlations. Discrimination assessments included specificity and reliability testing. Feasibility was assessed using time to form completion and proportion of missing data. RESULTS: Eighty-two CYP and their families were recruited; ten cognitive interviews and fifteen PROM/PREM test/retests were conducted. Truth: CYP and parents understood the PROM/PREM and felt important areas were covered. PROM criteria had high sensitivities (> 70%) against similar items on the CHU 9D, with the exception of fatigue (58%). Correlations between similar PROM and CHU 9D criteria were moderate to very strong (coefficients 0.40-0.82.) Discrimination: high specificities (> 70%) on corresponding PROM and CHU 9D domains. Feasibility: median completion times for PROM 60 s (IQR 38-75) and PREM 49 s (IQR 30-60) respectively. CONCLUSION: The CAPTURE-JIA PROM and PREM are valid and feasible in UK paediatric rheumatology clinics. Embedding routine collection into clinical care would be a major step towards improving quality of care.

Comparing Proxy, Adolescent, and Adult Assessments of Functional Ability in Adolescents With Juvenile Idiopathic Arthritis.

OBJECTIVE: In pediatric research, investigators rely on proxy reports of outcome, such as the proxy-completed Childhood Health Assessment Questionnaire (C-HAQ), to assess function in juvenile idiopathic arthritis (JIA). As children mature, they may self-complete the adult HAQ or the unvalidated adolescent-specific C-HAQ. It is unclear how these measures compare and whether they are directly interchangeable. The present study was undertaken to compare agreement between the proxy-completed C-HAQ, adolescent-specific C-HAQ, and the HAQ at initial presentation to pediatric rheumatologic care and 1 year following the first presentation in adolescents with JIA. METHODS: Adolescents ages 11-17 years participating in the Childhood Arthritis Prospective Study (CAPS), a UK multicenter inception cohort, were included. In a CAPS substudy, adolescents self-completed the adolescent-specific C-HAQ and the HAQ, and proxies simultaneously completed the proxy-completed C-HAQ at baseline and 1 year. Correlation and agreement between scores were assessed at baseline. Agreement and ability to similarly classify clinically important changes over time were assessed at 1 year following initial presentation to rheumatologic care. RESULTS: A total of 107 adolescents (adolescent-specific C-HAQ and HAQ) or their proxies (proxy-completed C-HAQ) had completed all 3 measures at baseline. Median age at diagnosis was 13 years, and 61% were female. Although the 3 scores demonstrated strong correlations (r > 0.8), they were not completely interchangeable, with agreement ranging between 70% and 80%. There was similar agreement between the changes in scores between baseline and 1 year. Using proxy-completed C-HAQ minimum clinically important cutoffs, the adolescent-specific C-HAQ and the HAQ similarly classified 80% to 90% of adolescents as having improved or worsened. CONCLUSION: While there is relatively high agreement and similar classification of change between HAQ and the 2 C-HAQ scores, these are not completely interchangeable. This impacts the comparison of function when measured in different ways over the lifespan.