Juvenile Idiopathic Arthritis Cohort Research Articles

Screening for comorbid autoimmune disease should be considered in children with ANA positive juvenile idiopathic arthritis – results from the south-Swedish juvenile idiopathic arthritis cohort

BackgroundThere is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis in a validated population-based JIA cohort in southern Sweden.MethodsAutoimmune comorbidities were evaluated in a pre-existing population-based JIA cohort of 302 participants, constituting of individuals diagnosed with a validated JIA diagnosis 2000–2010 in southern Sweden. The comorbidities were determined through analysis of diagnosis codes registered after the JIA diagnosis and until 2019. With the use of a reference population of 1510 age- and sex matched individuals, hazard ratios (HR) were calculated with Cox proportional models.ResultsDuring the study period, 7.7% of the JIA cohort received an autoimmune diagnosis after their JIA diagnosis. Individuals with JIA had an increased risk of autoimmune diseases in general (HR 4.11, 95% CI 2.13–7.91) within the first 7 years of disease, as well as separately for coeliac disease (HR 5.24, 95% CI 1.76–15.65) and hypothyroidism (HR 3.74, 95% CI 1.14–12.30) compared to the reference population. Antinuclear antibody (ANA) positivity was associated with a significantly increased risk of comorbid autoimmune disease in the JIA cohort, with HR 6.21 (95% CI 1.64–23.55) for ANA positive individuals.ConclusionsIndividuals with JIA have a significantly increased risk of being diagnosed with an autoimmune condition after receiving their JIA diagnosis compared to matched references. ANA positivity is associated with a further increased risk. Our results emphasize awareness in physicians of additional autoimmune disorders in individuals with JIA and advocate serological screening of autoimmune conditions during follow-up.

Uveitis as predictor of disease flare after the first anti-TNF withdrawal in oligoarticular and polyarticular juvenile idiopathic arthritis: a multicentric Italian experience.

TNF inhibitors (TNFi) have dramatically changed the prognosis of juvenile idiopathic arthritis (JIA), but it is not clear how and when to stop therapy. We aim to describe a multicentric cohort of JIA treated with adalimumab or etanercept who discontinued the treatment for persistent inactivity and to identify factors associated with relapse. In a multicentric Italian retrospective cohort study, medical records of patients with oligoarticular and polyarticular JIA were evaluated if they stopped therapy for persistent inactivity after the first TNFi. 136 patients were enrolled (102 female, median age at onset 3 years (range 1-15), of whom 55.9% had oligoarticular JIA, 40.4% uveitis and 72.8% ANA positivity. Adalimumab (59.3%) and etanercept (40.7%) were started at a median age of 6 years (range 1-16), TNFi were discontinued after a median time of 30 months (range 6-90), increasing the interval (76.5%), reducing the dose (18.4%) and abrupt discontinuation (16.9%). 79.4% of patients relapsed after a median time of 5 months (range 0.5-66). Patients with uveitis relapsed earlier (log rank χ² 16.4 p<0.0001), while patients who lengthened the interval of administration showed a later relapse (log rank χ² 6.95 p=0.008). Uveitis (HR 2.11 CI 1.34-3.31), age at onset (HR 0.909 CI 0.836-0.987), duration of tapering (HR 0.938 CI 0.893-0.985) and to have a persistent oligoarticular JIA (HR 0.597 CI 0.368-0.968) are significant predictors of disease relapse (Mantel-Cox χ² 34.23 p<0.001). Younger age at onset, uveitis, duration of tapering, and non-persistent oligoarticular JIA seem to be independent risk factors for earlier relapse after the first TNFi withdrawal.

Functional status of Indian children with juvenile idiopathic arthritis.

The functional disability status of Indian children with juvenile idiopathic arthritis is unidentified. In this cross-sectional study functional capacity of 60 juvenile idiopathic arthritis patients was assessed by the Childhood Health Assessment Questionnaire. A total of 60 juvenile idiopathic arthritis patients aged ranges from 1 to 12 years were recruited from a teaching hospital in eastern India. A childhood health assessment questionnaire was used to assess the functional health of children. Pain, patient's/parent's global assessment of general well-being, and physician's global assessment were assessed. Childhood health assessment questionnaire disability index for oligoarticular juvenile idiopathic arthritis differed significantly from polyarticular juvenile idiopathic arthritis (P < 0.001), systemic-onset juvenile idiopathic arthritis (P = 0.018) and undifferentiated juvenile idiopathic arthritis (P < 0.001). There was a good to a strong positive correlation between the childhood health assessment questionnaire disability index with pain score, patient's/parent's global assessment score, and physician global assessment score for the total juvenile idiopathic arthritis cohort. regarding juvenile idiopathic arthritis subtypes, significant correlations were noted between the childhood health assessment questionnaire disability index with the patient's/parent's global assessment and physician's global assessment (except for enthesitis-related arthritis). Assessment and documentation of the functional health status of juvenile idiopathic arthritis patients will improve the management of the disease.

Population Pharmacokinetics of Adalimumab in Juvenile Idiopathic Arthritis Patients: A Retrospective Cohort Study Using Clinical Care Data.

Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disorder that primarily affects the joints in children. Notably, it is known to co-occur with uveitis. Adalimumab, a monoclonal anti-TNF antibody, is effective in treating both conditions. A deeper understanding of the pharmacokinetics (PK) of adalimumab in JIA is crucial to advance in more personalized treatment approaches. The objective of this study is to evaluate the population PK profile of adalimumab in JIA and to explain causes for its variability. Adalimumab and antidrug antibody concentrations were retrospectively retrieved from the charts of patients with JIA. Initially, five literature-based population PK models of adalimumab were evaluated to assess their ability to describe the observed concentration-time profiles in the JIA cohort. These models included one specifically for the pediatric Crohn's disease population and four derived from studies in adult populations in healthy subjects and rheumatoid arthritis patients. Subsequently, a novel population PK model tailored to the JIA population was developed using NONMEM software. Monte Carlo simulations were then conducted utilizing the final PK model to visualize the concentration-time profile of adalimumab in patients with JIA and the impact of covariates. A cohort of 50 patients with JIA with 78 available adalimumab samples was assessed. The mean age was 11.8±3.9years, with a median body weight of 49kg (interquartile range 29.4-59.8kg). All literature models adequately described the concentration-time profiles in JIA. The best model, which was developed in patients with rheumatoid arthritis during the maintenance phase of treatment, served as a basis for estimating clearance in JIA, resulting in a value of 0.37L per day per 70kg. Patient body weight, antidrug antibodies, methotrexate use, CRP level, and comorbidity of uveitis were found to have a significant impact on adalimumab clearance, and these reduced the inter-patient variability from 58.6 to 28.0%. On steady state in the simulated patient population, the mean trough level was 7.4±5.5mg/L. The two dosing regimens of 20 and 40mg every other week, based on patients' body weight, resulted in comparable simulated overall drug exposure. Five literature models effectively described adalimumab PK in this pediatric cohort, highlighting the potential for extrapolating existing models to the pediatric population. The new JIA model confirmed the effect of several known covariates and found a novel association for drug clearance with methotrexate use (lower) and uveitis (higher), which might have clinical relevance for personalized dosing in JIA.

Comparative analysis of pediatric rheumatic patient growth patterns against norms: A cross-sectional study conducted in an Eastern Indian hospital

Background. Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease. Rheumatic diseases are a major cause of chronic illness in children around the world. SLE is a further prevalent inflammatory illness. Aims and objectives. To study different growth parameters of pediatric patients attending pediatric rheumatology clinic, to compare the growth parameters with age and sex matched controls and to compare growth among different types of pediatric rheumatic patients. Method. Different growth parameters and SMI (for children above 9 years) were recorded for patients attending pediatric rheumatology OPD having disease duration more than one year. Results. Among 121 patients, JIA was most common followed by SLE. Among JIA subtypes, SOJIA is most common. Mean age of presentation was earlier in SOJIA, late in JoAS. SLE patients had larger duration of illness prior to diagnosis than JIA patients. In JIA patients, mean height was significantly less than controls. SOJIA and polyarticular variety had significantly less weight and height compared to controls. SLE patients had significantly less weight and height compared to control. Anthropometric parameters were significantly more in SLE patients compared to JIA cohort. There was significantly more delayed puberty both in JIA and SLE patients compared to controls. Conclusion. JIA was most common, followed by SLE. Among JIA patients SOJIA variety was most common, JIA patients had significantly lower height than controls. SLE patients had significantly lower weight and height than controls. Delayed puberty was significantly more in both JIA and SLE patients compared to controls.

Disease activity trajectories from childhood to adulthood in the population-based Nordic juvenile idiopathic arthritis cohort

ObjectivesTo identify long-term disease activity trajectories from childhood to adulthood by using the clinical Juvenile Arthritis Disease Activity Score (cJADAS10) in juvenile idiopathic arthritis (JIA). Second, to evaluate the contribution...

Body mass index is associated with health-related quality of life and disease characteristics in young adults with juvenile idiopathic arthritis

BackgroundThere is a growing interest concerning the relationship between obesity and several medical conditions and inflammation. Nevertheless, there is a lack of studies regarding body mass index (BMI) among patients with juvenile idiopathic arthritis (JIA). Our aim was to investigate the impact of BMI on health-related quality of life (HRQoL) measured with a 36-Item Short Form Survey (SF-36), disease activity, and disability in young adults with JIA.MethodsThis study is a part of the population-based Nordic JIA cohort study. All newly diagnosed patients with JIA were recruited consecutively between 1997–2000 in specific regions in the Nordic countries. Patients in this sub-study were enrolled from 434 patients who attended their 18-year follow-up visit. Patients were classified according to the World Health Organization (WHO) into four groups based on their BMI. HRQoL, disease characteristics, disability, fatigue, sleep quality, physical activity, pain, comorbidities, and social status were assessed.ResultsThree hundred fifty-five patients from the original study cohort were enrolled in this study and 72% of them were female. Mean age was 23.9 (± SD 4.4) years. A significant relationship was found between the JIA categories and BMI groups (p = 0.014). A significant relationship was also found between BMI and disease activity scores (DAS28) (p = 0.028), disability (p < 0.001), pain (p = 0.013), fatigue (p = 0.035), and sleep quality (p = 0.044). Moreover, a significant relationship between BMI and HRQoL regarding bodily pain (p = 0.010) and general health (p = 0.048) was revealed when adjusted for sex, age, and JIA subtype.ConclusionWe discovered that BMI was significantly related to HRQoL, disease activity, and disability. BMI deserves more attention considering the treatment options and outcome of JIA in young adults.

Prevalence of tissue transglutaminase antibodies and IgA deficiency are not increased in juvenile idiopathic arthritis: a case-control study

BackgroundThe prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1–7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA. Our aim is to estimate the prevalence of IgA deficiency and tissue transglutaminase (tTG) IgA in a cohort of JIA followed in two large academic medical centers.MethodsSerum was collected and stored from all subjects and analyzed in a reference laboratory for total IgA (Quantitative Nephelometry) and tTG IgA antibody levels (Semi-Quantitative Enzyme-Linked Immunosorbent Assay). Fisher’s exact tests were performed for statistical significance. Risk estimates (odds ratios) with 95% confidence intervals were calculated.Results808 JIA cases and 140 controls were analyzed. Majority were non-Hispanic whites (72% vs. 68% p = 0.309). A total of 1.2% of cases were IgA deficient compared to none of the controls (p = 0.373). After excluding IgA deficient subjects, 2% of cases had tTG IgA ≥ 4u/mL compared to 3.6% of controls (p = 0.216) (OR = 0.5; 95% C.I = 0.1–1.4); and 0.8% of cases had tTG IgA > 10u/mL compared to 1.4% of controls (p = 0.627) (OR = 0.5; 95%C.I = 0.1–2.9).ConclusionsUsing the largest JIA cohort to date to investigate prevalence of celiac antibodies, the prevalence of positive tTG IgA was 0.8% and of IgA deficiency was 1.2%. The results did not demonstrate a higher prevalence of abnormal tTG IgA in JIA. The study did not support the routine screening of asymptomatic JIA patients for CD.

Coexistence of Autoimmune Thyroiditis and Juvenile Idiopathic Arthritis.

Autoimmune thyroid disease seems to occur more often in children with juvenile idiopathic arthritis (JIA) than in the general pediatric population. We investigated the prevalence of autoimmune thyroiditis (Hashimoto's thyroiditis) in young patients with JIA in Greece, which has not been evaluated previously. This descriptive study included patients with JIA followed up at the Pediatric Rheumatology Unit of the Second Department of Pediatrics of a tertiary general hospital in Thessaloniki, Greece. All patients were diagnosed and sorted according to the classification criteria of the International League of Associations for Rheumatology. The presence of thyroid autoantibodies was considered for determining autoimmune thyroiditis. Basic demographic, clinical, and laboratory data were collected from patients' records. Results: The analyzed sample comprised 130 patients with JIA (mean age 12.22years; 69.2% female). Most patients (70%) had a family history of at least one autoimmune disease and 30.8% of Hashimoto's thyroiditis. More than half (53.8%) had enthesitis-related arthritis (ERA), 22.3% had oligoarthritis, and 15.4% had psoriatic arthritis. Thyroid autoantibodies were detected in 22/130 patients (16.9%) suggesting autoimmune thyroiditis; most of these patients were euthyroid, whereas 3/22 (13.6%) had overt hypothyroidism determined by elevated levels of thyroid-stimulating hormone, decreased levels of free thyroxine, and typical ultrasound findings for Hashimoto's thyroiditis. The prevalence of clinical cases of Hashimoto's disease was 2.3%. The prevalence of autoimmune thyroiditis in our JIA cohort is higher compared to the general population and consistent with the previously reported range. Hence, investigation for thyroid autoimmunity should be included in the workup of patients with JIA.

Developing electronic health record algorithms that accurately identify patients with juvenile idiopathic arthritis

BackgroundThe objective of this study was to develop an algorithm that accurately identifies juvenile idiopathic arthritis (JIA) patients in the electronic health record (EHR). MethodsAlgorithms were developed in a de-identified EHR by searching for a priori JIA ICD-9 (International Classification of Diseases, Ninth Revision) and ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) codes and JIA-related keywords. Exclusion criteria were selected to remove other autoimmune diseases. A training set of 200 patients was randomly selected from patients containing ≥1 occurrence of a JIA ICD-9 or ICD-10-CM code. Case status was determined by a rheumatology clinic note documenting a JIA diagnosis before age 20. For each algorithm, positive predictive value (PPV), sensitivity, and F-measure were determined using the training set. ResultsWe developed 103 algorithms using combinations of ICD codes, keywords, and exclusion criteria. The algorithm requiring 4 or more counts of JIA ICD-9 or ICD-10-CM codes, keywords “enthesitis” and “uveitis”, and exclusion of ICD-9 or ICD-10-CM codes for systemic lupus erythematosus, dermatomyositis, polymyositis, and dermatopolymyositis had the highest PPV of 97% in the training set with an F-measure of 87%. There were 1,131 JIA cases returned by this algorithm. We validated the highest performing algorithm in a separate cohort from the training set with a PPV of 92% and an F-measure of 75%. ConclusionWe developed and validated JIA EHR algorithms with ICD-9 and ICD-10-CM codes to accurately identify a JIA cohort. Three algorithms achieved PPVs of 97%, each with different algorithm criteria, allowing for users to select an algorithm to best fit their research needs.

Subcutaneous Tocilizumab in Juvenile Idiopathic Arthritis Associated Uveitis

ABSTRACT Aim To describe the efficacy and safety of subcutaneous tocilizumab (SC-TCZ) in a cohort of juvenile idiopathic arthritis (JIA) patients with refractory uveitis. Methods Retrospective observational monocentric study including patients with JIA-associated uveitis treated with SC-TCZ. Results Thirteen patients were enrolled. The rate of uveitis flare/year per each patient was 1.6 ± 2.0 on the last bDMARDs before SC-TCZ, while it decreased to 0.4 ± 0.7 on SC-TCZ. Nine out of thirteen patients (69%) required the introduction of SC-TCZ only for active uveitis at baseline. Among these patients, five (56%) achieved complete treatment response. No uveitis relapses were observed in patients (4/13, 31%) requiring the introduction of SC-TCZ for active arthritis during follow-up (30.48 ± 21.6 months). Overall, SC-TCZ was safe, and no side effects were observed during the treatment. Conclusion SC-TCZ can be effective and safe in patients with JIA and uveitis recalcitrant to several bDMARDs.

The risk of depression and anxiety is not increased in individuals with juvenile idiopathic arthritis – results from the south-Swedish juvenile idiopathic arthritis cohort

BackgroundChildren with chronic diseases are reported to have increased risk of psychiatric comorbidity. Few studies have investigated this risk in juvenile idiopathic arthritis (JIA), with conflicting results. We performed a population-based, longitudinal cohort study of the risk of depression and anxiety in south-Swedish patients with juvenile arthritis.MethodsThe south-Swedish JIA cohort (n = 640), a population-based cohort with validated JIA diagnosis 1980 – 2010 and comparators, a reference group of 3200 individuals free from JIA, matched for sex, year of birth and residential region, was used. Data on comorbid diagnosis with depression or anxiety were obtained from the Skåne Healthcare Register, containing all healthcare contacts in the region, from 1998 to 2019. We used Cox proportional models for the calculation of hazard ratios.ResultsDuring the study period, 1998 to 2019, 93 (14.5%) of the individuals in the JIA group were diagnosed with depression, and 111 (17.3%) with anxiety. Corresponding numbers among the references was 474 (14.8%) with depression and 557 (17.4%) with anxiety. Hazard ratio for depression was 1.1 (95% CI 0.9 – 1.5) in females and 0.8 (95% CI 0.5 – 1.4) in males, and for anxiety 1.2 (95% CI 0.9 – 1.5) in females and 0.6 (95% CI 0.4 – 1.1) in males. There were no statistically significant hazard ratios when analyzing subgroups of JIA patients with long disease duration or treatment with disease-modifying antirheumatic drugs.ConclusionsIndividuals with JIA do not have any statistically increased risk of being diagnosed with depression or anxiety compared to matched references.

Development of Inflammatory Bowel Disease in Children With Juvenile Idiopathic Arthritis Treated With Biologics.

The aim of our study was to describe the distinct features of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) patients and to identify risk factors for its development. Data from the German biologics in pediatric rheumatology registry (Biologika in der Kinderrheumatologie) collected between 2001 and 2021 were analyzed retrospectively. In 5009 JIA patients, 28 developed confirmed IBD before the age of 18 years: 23 (82.1%) with Crohn disease (CD), 4 (14.3%) with ulcerative colitis (UC), and 1 (3.6%) with IBD-unclassified (IBD-U). The incident rate of IBD during 20 years of observation was 0.56% (0.46% for CD, 0.08% for UC, and 0.02% for IBD-U), of whom 20.3% were HLA-B27 positive, 25% had enthesitis-related arthritis, and 14.3% psoriatic arthritis. Within 90 days before IBD diagnosis, 82.1% (n = 23) received treatment with etanercept (ETA), 39.3% (n = 11) non-steroidal anti-inflammatory drugs, 17.9% (n = 5) systemic corticosteroids, 8 (28.6%) methotrexate (MTX), 14.3% (n = 4) sulfasalazine, 10.7% (n = 3) leflunomide, and 3.6% (n = 1) adalimumab and infliximab, respectively. The incidence of IBD was lower in patients treated with MTX, but higher in patients treated with ETA except if ETA was combined with MTX. Also in patients on leflunomide or sulfasalazine, the IBD incidence was higher. In our JIA cohort, an increased IBD incidence is observed compared to the general population, and the ratio of CD to UC is markedly higher hinting at a distinct phenotype of IBD. Pretreatment with MTX seems to be protective. Treatment with ETA does not prevent IBD development and JIA patients treated with leflunomide and sulfasalazine may be at an increased risk for IBD development.

Transitioning patients with juvenile idiopathic arthritis to adult care: the Nordic experience

BackgroundWith juvenile idiopathic arthritis (JIA), there are several protocols and practices used worldwide for the transition from paediatric to adult care. In this study, we examined the transferral rates and disease activity after transition, as well as the disease- and health-related outcomes. We also introduce the transition practices employed in the Nordic countries.MethodsThe study population comprised 408 participants with a disease onset from 1997 to 2000 who attended an 18-year follow-up visit in this population-based Nordic JIA cohort study. The patients were retrospectively divided into three subgroups: Patients transferred directly from paediatric care to adult rheumatology care, patients referred there later, and patients never transferred during the 18-year follow-up period.ResultsOne hundred and sixty-three (40%) JIA patients had been directly transferred to an adult clinic. The cumulative transition rate was 52%, but there were significant differences between the participating centres. Fifty patients had later been referred to an adult clinic. Among the 195 patients who had never been transferred, 39% were found to have disease activity at the study visit.ConclusionThis study highlights the need to reconsider transition practices to avoid our undesirable finding of patients with disease activity in JIA, but no appropriate health care follow-up.

P48 Service evaluation of disease burden of, and damage caused by, wrist arthritis in a single centre paediatric cohort of JIA

Introduction/BackgroundWrist synovitis is associated with more severe disease and less drug-free remission periods, therefore, the objective of this study was to investigate the demographic, disease course, and complexity of wrist disease in children being treated for Juvenile Idiopathic Arthritis (JIA).Description/MethodA single-centre, retrospective case note review of all children and adolescents diagnosed with JIA, who received steroid joint injections of their wrists from 2014 to 2019. All patients received standard therapy and underwent regular follow-up at Birmingham Children’s Hospital. Inclusion criteria were those with an established diagnosis of any JIA-subtype according to the International League of Associations for Rheumatology (ILAR) classification. Patients were excluded if (i) the data were incomplete, (ii) they were over the age of 16y at diagnosis, or (iii) the eventual diagnosis was not JIA. Clinical information was gathered from case notes, departmental databases and hospital clinical systems on to a standardised proforma. Information collected were demographics, JIA subtype, immunology, age at diagnosis, disease duration, number of wrist injections and outcome of every wrist MRI performed. All treatments including intraarticular injections were administered by a paediatric Rheumatologist while MRIs were reviewed by an experienced senior Radiologist.Discussion/ResultsOf all 94 eligible patients, 88 (94%) were included in this study; 71 girls, with a mean age at diagnosis of 6 years (0-15 years). Wrist arthritis was more common in seronegative polyarthritis (40%) and extended oligoarthritis (23%) but least pronounced in Enthesitis-related arthritis (2%). 85 (95.6%) received Methotrexate therapy with a mean of 10 months from time of diagnosis. 77 patients (88%) required a step-up from MTX, with Etanercept (88%) being the most popular option as a first-line biologics, followed by Adalimumab (11%). All patients who had Adalimumab as a first biologics had evidence of uveitis.Wrist disease was present at diagnosis in 60/88 (68%) of our cohort. 66 patients (75%) had bilateral wrist disease. Over one-quarter of patients who developed wrist arthritis within the first year of diagnosis were young children (0-2 years). A second predominate group was adolescent (10-15 years) accounting for 33% of our cohort. The mean (IQR) duration between diagnosis and first clinical evidence of wrist synovitis was 15 months (1–17). Patients had a median of 3 years from diagnosis until development of first radiological evidence of erosive changes.12 children (14%) from this cohort underwent a laparoscopic synovectomy for their wrist damage between 2017 and 2021, out of which 9 had polyarticular involvement while two had extended and one had persistent oligoarticular arthritis. Half of the patients reported improvement in pain and Health Assessment Questionnaire (HAQ) scores after synovectomy, while three remained stable at 0 score, and 3 had insufficient data.Key learning points/ConclusionTreatment of wrist arthritis can be challenging to both professionals and health care systems, emphasizing the need for clear steps to improve early recognition and treatment. Wrist disease at presentation was relatively common in our cohort and damage once occurred was irreversible with patients continuing to have ongoing disease activity despite optimization of their treatment. Furthermore, MRI as shown in our analysis, can accurately detect early erosive changes and inform management decision.

OA31 Successes and challenges in harmonising 4 national Juvenile Idiopathic Arthritis cohorts: an example from CLUSTER consortium

Introduction/BackgroundThe CLUSTER consortium aims to identify biomarkers and strata that improve personalised treatments for JIA/JIA-uveitis. By bringing together knowledge and data, CLUSTER can conduct novel analyses in this rare, heterogeneous disease. Data harmonisation across existing JIA cohorts facilitates new, larger datasets that would otherwise take years to collect; however, challenges exist as datasets are often collected autonomously. Here we present progress towards a large-scale, unique JIA data resource, bringing together treatment data from 4 real-world JIA treatment studies.Description/MethodFour studies (CAPS, CHARMS, BCRD and BSPAR-ETN; the latter two being part of the UK JIA Biologics register) contributed data into CLUSTER.We created two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi). Variables were selected based on a previously developed core dataset, accounting for different levels of granularity across studies. The same inclusion and exclusion criteria were agreed for both datasets, designed to allow for combined analysis of these.OpenPseudonymiser software encrypted NHS numbers - these were matched cross-study to identify duplicates and checked against known duplicate lists. Errors in NHS numbers and existing duplicate matches were identified and corrected. Each NHS number was assigned a CLUSTER ID, meaning 1 child has the same ID across all relevant studies such that children contributing similar data across multiple studies could be identified.Discussion/ResultsA total of 7013 records (from 5435 individuals) were identified; of which 2882 (41%, corresponding to 1304 individuals) represented the same child across >1 study. 197 individuals had duplicate records within 1 study, 961 in 2 studies, 142 in 3, and 4 children had duplicate records in all 4 studies.After removing 350 MTX and 605 TNFi duplicate entries, the final datasets contain 2899 and 2401 unique MTX and TNFi patients respectively; 1018 are in both datasets having received both treatments. Missingness across core outcome variables ranged from 10% (active joint count MTX timepoint 2) to 60% (physician VAS TNFi timepoint 2) and was not improved through combining datasets with duplicate entries. Specificity in some variables was lost to allow integration by combining data using least common denominators (e.g. ethnicity captured as Caucasian/Non-Caucasian, despite more specific categories available in some studies). Key learning points/ConclusionCombining data across studies has achieved dataset sizes rarely seen in JIA, which is invaluable to progressing research into personalised treatments and disease outcomes. However, losing specificity in some variables and missingness (a known challenge in observational data) and their impact on future analyses requires further consideration. Ongoing work includes identifying patients with both clinical and biological data that can be combined for more in-depth analyses. Both datasets are available for researchers to use via the CLUSTER Consortium Data Management Committee.

An overview of the relationship between juvenile idiopathic arthritis and potential environmental risk factors: Do early childhood habits or habitat play a role in the affair?

The current study was undertaken to evaluate the influence of breastfeeding on the development and outcome measures of juvenile idiopathic arthritis (JIA). The second aim was to determine the consequences of particular sociodemographic and sociocultural characteristics and nutritional behavior of early childhood on JIA. The study includes the patients diagnosed with JIA and regularly followed up at the Department of Pediatric Rheumatology in Istanbul University-Cerrahpasa. The comparison group consisted of healthy subjects and patients with juvenile systemic lupus erythematosus (jSLE). A face-to-face survey method was conducted with the parents of the participants between February 1, 2021, and September 1, 2021. The mean age of the JIA cohort (n=324) was 12.2 ± 4.7 years, with a female ratio of 64.8%. The breastfeeding rate differed from the control groups (253 healthy subjects and 88 patients with jSLE) but was higher with a value of 94.8%. There was no difference between the groups (P=.097, P=.064) or within the subgroups of JIA (P=.12) regarding breastfeeding duration. Cow's milk introduction time (P=.02, P=.0001), household pet-keeping (P=.001), income level (P=.0001), maternal literacy (P=0.013) made a statistical difference vs the control groups. No relationship was established between the rate or duration of breastfeeding and the development or severity of JIA. The early introduction of cow's milk was found to be higher in the patient cohorts. The income level and maternal literacy appeared to be relevant with the high disability and damage scores, and frequent relapse rates. Secondhand smoking, higher in JIA, may prompt the basis of primary preventable strategies in JIA.

Abdominal pain in Finnish young adults with juvenile idiopathic arthritis

Objectives Abdominal pain (AP) is a common feature in the general population. However, in patients with juvenile idiopathic arthritis (JIA) AP has scantily been studied. Among other reasons, gastrointestinal symptoms may present as side effects due to the medical treatment of JIA. The aim of the study was to explore the frequency of AP and its relationship to disease components and health-related quality of life (HRQoL) among young adults with JIA. Methods This study included a cohort of 97 Finnish patients belonging to the population-based Nordic JIA cohort at their 17-year follow-up study visit. Mean age of the patients was 23 years. AP, functional status, fatigue, HRQoL, disease characteristics of JIA, and comorbidities were evaluated. AP was classified into three categories according to frequency: (1) never, (2) seldom (one to three times a month) and (3) frequent (at least once a week). Results About 48 (50%) young adults with JIA reported AP. Seldom AP was reported by 37 (38%), and frequent AP by 11 (11%) patients. AP was significantly associated with fatigue, female gender, functional status and arthritis-related pain. Patients having frequent AP reported lower HRQoL. AP was associated with the use of methotrexate and sulfasalazine, but not with nonsteroidal anti-inflammatory drugs (NSAIDs). Conclusion AP is an important complaint in young adults with JIA and is associated with fatigue, female gender, methotrexate and sulfasalazine use. Patients with JIA reporting frequent AP with lower functional status and higher arthritis-related pain values have lower HRQoL.

OA19 Successes and challenges in harmonising four national juvenile idiopathic arthritis cohorts: an example from CLUSTER consortium

Abstract Background/Aims The CLUSTER consortium aims to identify biomarkers and strata that improve personalised treatments for JIA/JIA-uveitis. By bringing together knowledge and data, CLUSTER can conduct novel analyses in this rare, heterogeneous disease. Data harmonisation across existing JIA cohorts facilitates new, larger datasets that would otherwise take years to collect; however, challenges exist as datasets are often collected autonomously. Here we present progress towards a large-scale, unique JIA data resource, bringing together treatment data from four real-world JIA treatment studies. Methods Four studies (CAPS, CHARMS, BCRD and BSPAR-ETN; the latter two being part of the UK JIA Biologics register) contributed data into CLUSTER. We created two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi). Variables were selected based on a previously developed core dataset, accounting for different levels of granularity across studies. The same inclusion and exclusion criteria were agreed for both datasets, designed to allow for combined analysis of these. OpenPseudonymiser software encrypted NHS numbers - these were matched cross-study to identify duplicates and checked against known duplicate lists. Errors in NHS numbers and existing duplicate matches were identified and corrected. Each NHS number was assigned a CLUSTER ID, meaning one child has the same ID across all relevant studies such that children contributing similar data across multiple studies could be identified. Results A total of 7013 records (from 5435 individuals) were identified, of which 2882 (41%, corresponding to 1304 individuals) represented the same child across &amp;gt;1 study. 197 individuals had duplicate records within one study, 961 in two studies, 142 in three, and four children had duplicate records in all four studies. After removing 350 MTX and 605 TNFi duplicate entries, the final datasets contain 2899 and 2401 unique MTX and TNFi patients respectively; 1018 are in both datasets having received both treatments. Missingness across core outcome variables ranged from 10% (active joint count MTX timepoint 2) to 60% (physician VAS TNFi timepoint 2) and was not improved through combining datasets with duplicate entries. Specificity in some variables was lost to allow integration by combining data using least common denominators (e.g. ethnicity captured as Caucasian/Non-Caucasian, despite more specific categories available in some studies). Conclusion Combining data across studies has achieved dataset sizes rarely seen in JIA, which is invaluable to progressing research into personalised treatments and disease outcomes. However, losing specificity in some variables and missingness (a known challenge in observational data) and their impact on future analyses requires further consideration. Ongoing work includes identifying patients with both clinical and biological data that can be combined for more in-depth analyses. Both datasets are available for researchers to use via the CLUSTER Consortium Data Management Committee. Disclosure S. Lawson-Tovey: None. L.R. Wedderburn: Consultancies; L.W. reports consulting fees from Pfizer unrelated to this work. Grants/research support; CLUSTER consortium receives support from AbbVie, UCB, Pfizer, Sobi and GSK. N. Geifman: None. M. Barnes: None. K.L. Hyrich: Grants/research support; KLH reports grant income from BMS, UCB, and Pfizer. Other; KLH reports non-personal speaker's fees from Abbvie.

Evaluation of flare rate and reduction strategies for bDMARDs in juvenile idiopathic arthritis: real world data from a single-centre cohort.

This study aimed to determine the flare rate (FR) in a cohort of Juvenile Idiopathic Arthritis (JIA) patients with tapered or abruptly discontinued biologic disease-modifying anti-rheumatic drugs (bDMARDs) and to identify predictors of flare. This retrospective observational study included 191 bDMARD dose-reduction events in patients with JIA followed-up at a referral hospital during the period 2000-2019. FR was analysed according to reduction strategies. To identify predictors of flare, Kaplan-Meier and Cox-regression models were plotted at 6months (6m), 12months (12m) and 24months (24m) following tapering (TP) or withdrawal (WD). 165 episodes of TP and 71 episodes of WD were included; 45 episodes where treatment was withdrawn after TP were included in both strategies. FR after TP was 13.4% at 6m and increased up to 26.6% at 12m and 51.4% at 24m. After WD, FR was higher, 52.1% of events had a flare at 6m and 67.6% at 12m. Previous TP did not increase time in remission after WD of bDMARDs in the Kaplan-Meier analysis. Factors associated with flares were identified after TP at 6m: female sex, higher number of previous bDMARDs and longer time on bDMARD treatment were positively associated with flares. Polyarticular subtype and younger age at diagnosis were associated with flares at 12 and 24m after TP. No factors were identified in multivariable analysis after WD. TP is a successful strategy to maintain remission with lower bDMARD doses. Previous TP of bDMARDs does not seem to increase time in remission after WD.