Arthritis Research Research Articles

The evaluation of bone marrow edema in sacroiliac joint in patients with ankylosing spondylitis using magnetic resonance imaging Dixon sequence

BackgroundBone marrow edema of the sacroiliac joint is the early imaging manifestation, an indicator of inflammatory activity of ankylosing spondylitis (AS) (Yang R, et. al. Medicine (Baltimore) 98:e14620, 2019).ObjectiveThe aim of the study was to investigate the value of magnetic resonance imaging (MRI) Dixon sequence in the diagnosis of marrow edema of the sacroiliac joint in patients with AS.MethodsForty-five patients with AS admitted in our hospital between November 2016 and February 2019 were selected retrospectively as the case group. Forty-five healthy subjects recruited between November 2016 and February 2019 served as the control group. Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were recorded after admission to the hospital. The Dixon sequence water-fat ratio of the iliac and sacral surfaces of the bilateral sacroiliac joints in the study group were compared with indicators above in order to find the correlation.ResultsThe water-fat ratio under the bilateral sacroiliac joints on Dixon sequence images in the case group was significantly higher than that in the healthy control group (P<0.05). The Dixon sequence water-fat ratio of the iliac and sacral surfaces of the bilateral sacroiliac joints in the study group were positively correlated with spinal arthritis research (SPARCC), BASFI and BASDAI score (all P < 0.05), but did not correlate with ESR and CRP.ConclusionThe water-fat ratio of magnetic resonance Dixon sequence can be used as a reference index to evaluate the degree of bone marrow edema in active stage of sacroiliac arthritis.

Impact of the COVID-19 pandemic on juvenile idiopathic arthritis presentation and research recruitment: results from the CAPRI registry.

ObjectiveThe COVID-19 pandemic has disrupted healthcare delivery and clinical research worldwide, with data from areas most affected demonstrating an impact on rheumatology care. This study aimed to characterize the impact of the pandemic on the initial presentation of JIA and JIA-related research in Canada.MethodsData collected from the Canadian Alliance of Pediatric Rheumatology Investigators JIA Registry from the year pre-pandemic (11 March 2019 to 10 March 2020) was compared with data collected during the first year of the pandemic (11 March 2020 to 10 March 2021). Outcomes included time from symptom onset to first assessment, disease severity at presentation and registry recruitment. Proportions and medians were used to describe categorical and continuous variables, respectively.ResultsThe median time from symptom onset to first assessment was 138 (IQR 64–365) days pre-pandemic vs 146 (IQR 83–359) days during the pandemic. The JIA category frequencies remained overall stable (44% oligoarticular JIA pre-pandemic, 46.8% pandemic), except for systemic JIA (12 cases pre-pandemic, 1 pandemic). Clinical features, disease activity (cJADAS10), disability (CHAQ) and quality of life (JAQQ) scores were similar between the two cohorts. Pre-pandemic, 225 patients were enrolled, compared with 111 in the pandemic year, with the greatest decrease from March to June 2020.ConclusionsWe did not observe the anticipated delay in time to presentation or increased severity at presentation, suggesting that, within Canada, care adapted well to provide support to new patient consults without negative impacts. The COVID-19 pandemic was associated with an initial 50% decrease in registry enrolment but has since improved.

A Girl with Limp and Rash on the Palms and Soles.

A Girl with Limp and Rash on the Palms and Soles.

Differences in rituximab use between pediatric rheumatologists and nephrologists for the treatment of refractory lupus nephritis and renal flare in childhood-onset SLE

BackgroundConsensus treatment plans have been developed for induction therapy of newly diagnosed proliferative lupus nephritis (LN) in childhood-onset systemic lupus erythematosus. However, patients who do not respond to initial therapy, or who develop renal flare after remission, warrant escalation of treatment. Our objective was to assess current practices of pediatric nephrologists and rheumatologists in North America in treatment of refractory proliferative LN and flare.MethodsMembers of Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the American Society for Pediatric Nephrology (ASPN) were surveyed in November 2015 to assess therapy choices (other than modifying steroid dosing) and level of agreement between rheumatologists and nephrologists for proliferative LN patients. Two cases were presented: (1) refractory disease after induction treatment with corticosteroid and cyclophosphamide (CYC) and (2) nephritis flare after initial response to treatment. Survey respondents chose treatments for three follow up scenarios for each case that varied by severity of presentation. Treatment options included CYC, mycophenolate mofetil (MMF), rituximab (RTX), and others, alone or in combination.ResultsSeventy-six respondents from ASPN and foty-one respondents from CARRA represented approximately 15 % of the eligible members from each organization. Treatment choices between nephrologists and rheumatologists were highly variable and received greater than 50 % agreement for an individual treatment choice in only the following 2 of 6 follow up scenarios: 59 % of nephrologists, but only 38 % of rheumatologists, chose increasing dose of MMF in the case of LN refractory to induction therapy with proteinuria, hematuria, and improved serum creatinine. In a follow up scenario showing severe renal flare after achieving remission with induction therapy, 58 % of rheumatologists chose CYC and RTX combination therapy, whereas the top choice for nephrologists (43 %) was CYC alone. Rheumatologists in comparison to nephrologists chose more therapy options that contained RTX in all follow up scenarios except one (p < 0.05).ConclusionsTherapy choices for pediatric rheumatologists and nephrologists in the treatment of refractory LN or LN flare were highly variable with rheumatologists more often choosing rituximab. Further investigation is necessary to delineate the reasons behind this finding. This study highlights the importance of collaborative efforts in developing consensus treatment plans for pediatric LN.

Improved Disease Course Associated With Early Initiation of Biologics in Polyarticular Juvenile Idiopathic Arthritis: Trajectory Analysis of a Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment Plans Study.

To investigate the effects of early introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) on the disease course in untreated polyarticular juvenile idiopathic arthritis (JIA). We analyzed data on patients with polyarticular JIA participating in the Start Time Optimization of Biologics in Polyarticular JIA (STOP-JIA) study (n = 400) and a comparator cohort (n = 248) from the Childhood Arthritis and Rheumatology Research Alliance Registry. Latent class trajectory modeling (LCTM) was applied to identify subgroups of patients with distinct disease courses based on disease activity (clinical Juvenile Arthritis Disease Activity Score in 10 joints) over 12 months from baseline. In the STOP-JIA study, 198 subjects (49.5%) received bDMARDs within 3 months of baseline assessment. LCTM analyses generated 3 latent classes representing 3 distinct disease trajectories, characterized by slow, moderate, or rapid disease activity improvement over time. Subjects in the rapid improvement trajectory attained inactive disease within 6 months from baseline. Odds of being in the rapid improvement trajectory versus the slow improvement trajectory were 3.6 times as high (95% confidence interval 1.32-10.0; P = 0.013) for those treated with bDMARDs ≤3 months from baseline compared with subjects who started bDMARDs >3 months after baseline, after adjusting for demographic characteristics, clinical attributes, and baseline disease activity. Shorter disease duration at first rheumatology visit approached statistical significance as a predictor of favorable trajectory without bDMARD treatment. Starting bDMARDs within 3 months of baseline assessment is associated with more rapid achievement of inactive disease in subjects with untreated polyarticular JIA. These results demonstrate the utility of trajectory analysis of disease course as a method for determining treatment efficacy.

Patterns of etanercept use in juvenile idiopathic arthritis in the Childhood Arthritis and Rheumatology Research Alliance Registry

BackgroundWe aimed to characterize etanercept (ETN) use in juvenile idiopathic arthritis (JIA) patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.MethodsThe CARRA Registry is a convenience cohort of patients with paediatric onset rheumatic diseases, including JIA. JIA patients treated with ETN for whom the month and year of ETN initiation were available were included. Patterns of ETN and methotrexate (MTX) use were categorized as follows: combination therapy (ETN and MTX started concurrently), step-up therapy (MTX started first and ETN added later), switchers (MTX started and then stopped when or before ETN started), MTX add-on (ETN started first and MTX added later), and ETN only (no MTX use). Data were described using parametric and non-parametric statistics as appropriate.ResultsTwo thousand thirty-two of the five thousand six hundred forty-one patients with JIA met inclusion criteria (74% female, median age at diagnosis 6.0 years [interquartile range 2.0, 11.0]. Most patients (66.9%) were treated with a non-biologic disease modifying anti-rheumatic drug (DMARD), primarily MTX, prior to ETN. There was significant variability in patterns of MTX use prior to starting ETN. Step-up therapy was the most common approach. Only 34.0% of persistent oligoarticular JIA patients continued treatment with a non-biologic DMARD 3 months or more after ETN initiation. ETN persistence overall was 66.3, 49.4, and 37.3% at 24, 36 and 48 months respectively. ETN persistence among spondyloarthritis patients (enthesitis related arthritis and psoriatic JIA) varied by MTX initiation pattern, with higher ETN persistence rates in those who initiated combination therapy (68.9%) and switchers/ETN only (73.3%) patients compared to step-up (65.4%) and MTX add-on (51.1%) therapy.ConclusionThis study characterizes contemporary patterns of ETN use in the CARRA Registry. Treatment was largely in keeping with American College of Rheumatology guidelines.

Community poverty level influences time to first pediatric rheumatology appointment in Polyarticular Juvenile Idiopathic Arthritis

BackgroundThe impact of social determinants of health on children with polyarticular juvenile idiopathic arthritis (pJIA) is poorly understood. Prompt initiation of treatment for pJIA is important to prevent disease morbidity; however, a potential barrier to early treatment of pJIAs is delayed presentation to a pediatric rheumatologist. We examined the impact of community poverty level, a key social determinant of health, on time from patient reported symptom onset to first pediatric rheumatology visit among pJIA patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry.MethodsThis is a cohort study of pJIA patients in the CARRA registry who lived in the United States from July 2015–February 2020. The primary exposure was community poverty level derived by geocoding patient addresses. The primary outcome was time to first rheumatology appointment. Kaplan-Meier analysis was performed to analyze time to first rheumatologist visit, stratified by community poverty and family income. Log-rank tests were used to identify differences between groups. Adjusted cox proportional-hazards models were used to determine the relationship between community poverty level and time from onset of disease symptoms to date first seen by rheumatologist.ResultsA total of 1684 patients with pJIA meeting study inclusion and exclusion criteria were identified. Median age of onset of pJIA was 7 years (IQR 3, 11), 79% were female, 17.6% identified as minority race and/or ethnicity, and 19% were from communities with ≥20% community poverty level. Kaplan-Meier analysis by community poverty level (< 20% vs ≥20%) yielded no significant differences with time to initial presentation to a pediatric rheumatologist (p = 0.6). The Cox proportional hazards model showed that patients with ≥20% community poverty level were 19% less likely (adjusted HR 0.81, 95% CI 0.67–0.99, p = 0.038) to be seen by a rheumatologist compared to patients with < 20% community poverty level, at the same time point, after adjusting for sex, race/ethnicity, insurance, education level, morning stiffness, RF status, and baseline CHAQ.ConclusionIn this study of pJIA patients in the CARRA registry, increased community poverty level is associated with longer time to presentation to a pediatric rheumatologist after symptom onset.

Causal Relationship Between Parathyroid Hormone and the Risk of Osteoarthritis: A Mendelian Randomization Study

BackgroundPrevious studies have demonstrated an inverse association between parathyroid hormone (PTH) and the risk of osteoarthritis (OA). However, it remains unknown whether such association reflects causality. We aimed to apply a Mendelian randomization (MR) approach to investigate the causal association between PTH and OA.Materials and MethodsWe performed a two-sample MR analysis using summary statistics from 13 cohorts (PTH, N = 29,155) and a recent genome-wide association study meta-analysis (OA, N = 455,221) by the UK Biobank and Arthritis Research UK OA Genetics (arcOGEN). MR analyses were carried out mainly using the inverse-variance-weighted method. Sensitivity analyses were performed to test the robustness of the associations using the weighted median method, the MR–Egger method, and “leave-one-out” analysis. Analyses were performed again to test whether the associations remained statistically significant after excluding any outlier variants that were detected using the MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) test.ResultsFive single-nucleotide polymorphisms (SNPs) were selected as instrumental variables at the genome-wide significance threshold (p < 5 × 10–8). The causal effect between PTH and OA was genetically predicted using the inverse-variance-weighted method (odds ratio = 0.67, 95% confidence interval: 0.50–0.90; p = 0.008). This result was borne out using the weighted median method (odds ratio = 0.73, 95% confidence interval: 0.60–0.90; p = 0.004). The causality remained robust after discarding the outlier variants as well as SNPs associated with confounding factors.ConclusionMR analysis supported a potential causative relationship between decreased serum circulating PTH and a higher risk of hip and knee OA.

Principles of pediatric lupus nephritis in a prospective contemporary multi-center cohort.

Lupus nephritis (LN) is a life-threatening manifestation of systemic lupus erythematosus (SLE) and is more common in children than adults. The epidemiology and management of childhood-onset SLE (cSLE) have changed over time, prompting the need to reassess expected outcomes. The purpose of this study is to use the Childhood Arthritis and Rheumatology Research Alliance (CARRA) prospective registry to validate historical principles of LN in a contemporary, real-world cohort. After an extensive literature review, six principles of LN in cSLE were identified. The CARRA registry was queried to evaluate these principles in determining the rate of LN in cSLE, median time from cSLE diagnosis to LN, short-term renal outcomes, and frequency of rituximab as an induction therapy. Of the 677 cSLE patients in the CARRA registry, 32% had documented LN. Decline in kidney function was more common in Black cSLE patients than non-Black patients (p = 0.04). Black race was associated with worse short-term renal outcomes. In short-term follow up, most children with LN had unchanged or improved kidney function, and end stage kidney disease (ESKD) was rare. Ongoing follow-up of cSLE patients in the CARRA registry will be necessary to evaluate long-term outcomes to inform risk, management, and prognosis of LN in cSLE.

Telemedicine use by pediatric rheumatologists during the COVID-19 pandemic

BackgroundTo characterize various aspects of telemedicine use by pediatric rheumatology providers during the recent pandemic including provider acceptability of telehealth practices, clinical reliability, and clinical appropriateness.MethodsAn electronic survey was generated and disseminated amongst the Childhood Arthritis and Rheumatology Research Alliance (CARRA) listserv (n = 547). Survey items were analyzed via descriptive statistics by question.ResultsThe survey response rate was 40.8% (n = 223) with the majority of respondents in an attending-level role. We observed that musculoskeletal components of the exam were rated as the most reliable components of a telemedicine exam and 86.5% of survey respondents reported engaging the patient or patient caregiver to help conduct the virtual exam. However, 65.7% of providers reported not being able to elicit the information needed from a telemedicine visit to make a complete clinical assessment. We also noted areas of disagreement regarding areas of patient engagement and confidentiality. We found that approximately one-third (35.8%) of those surveyed felt that their level of burnout was increased due to telemedicine.ConclusionIn general, providers found exam reliability (specifically around focused musculoskeletal elements) in telemedicine visits but overall felt that they were unable to generate the information needed to generate a complete clinical assessment. Additionally, there were suggestions that patient engagement and confidentiality varied during telemedicine visits when compared to in-person clinical visits. Further qualitative work is needed to fully explore telemedicine use in pediatric rheumatology.

Impact of the Season of Birth on the Development of Juvenile Idiopathic Arthritis in the United States: A Nationwide Registry-based Study.

Autoimmune disorders result from the interplay of genetic and environmental factors. Many autoimmune disorders are associated with specific seasons of birth, implicating a role for environmental determinants in their etiopathology. We investigated if there is an association between the season of birth and the development of juvenile idiopathic arthritis (JIA). Birth data from 10,913 children with JIA enrolled at 62 Childhood Arthritis and Rheumatology Research Alliance Registry sites was compared with 109,066,226 US births from the same period using a chi-square goodness-of-fit test. Season of birth of the JIA cohort was compared to the US population estimate using a 2-sided 1-sample test for a binomial proportion and corrected for multiple comparisons. Secondary analysis was performed for JIA categories, age of onset, and month of birth. A greater proportion of children with JIA were born in winter (January-March) compared to the US general population (25.72% vs 24.08%; corrected P < 0.0001). This observation was also true after stratifying for age of onset (≤ or > 6 yrs). When analyzed by the month of birth, a greater proportion of children with JIA were born in January compared to the US population (9.44% vs 8.13%; corrected P < 0.0001). Relative to the general population, children with JIA are more often born in the winter, and specifically in the month of January. These observations support the hypothesis that seasonal variations in exposures during the gestational and/or early postnatal periods may contribute to development of JIA.

Arthritis Research UK Musculoskeletal Health Questionnaire (MSK-HQ) as an indicator of health status and health literacy in an urban setting

Objective: The Musculoskeletal Health Questionnaire (MSK-HQ) is a standardized musculoskeletal outcomes measure for the health status of patients with various musculoskeletal conditions. The objective of this study was to investigate the patient reported outcomes using the MSK-HQ in an urban patient population that has a unique set of needs. Specifically, the patient population in the South Bronx, New York has defining demographic and clinical characteristics of low-income, English as a second language, and high rates of obesity. Moreover, patients in this community are at high risk for low rates of health literacy. This study aims to use the MSK-HQ to identify how living in an urban setting impacts patients’ access to affordable and quality care. Methods: Patients (n=83) at the BronxCare Health System Department of Orthopaedics outpatient clinics were surveyed using the Arthritis Research UK Musculoskeletal Health Questionnaire (MSK-HQ). The total number of patients were divided into 4 cohorts based on their musculoskeletal condition; spine (n=21), hand and upper extremity (n=29), sports medicine (n=17), and arthroplasty candidates (n=16). The MSK-HQ is a 15-item survey that assesses musculoskeletal disability and levels of physical activity. The minimum score of the questionnaire is 0 and maximum score is 56. A decrease in the total score indicates an decrease in Patient Reported Outcome Measures (PROMs). The patients were individually screened with the questionnaire. Those that declared English as a second language were screened with the aid of a telephone translator. Results: The mean age was 51.6 years old ± 14.1 years. There were 57 (70.37%) females and 24 (29.63%). The mean BMI was 31.0 ± 7.9. There were 12 (14.81%) patients that classified under normal weight conditions, 32 (39.51%) overweight, and 37 (45.68%) obese. The mean Patient Reported Outcome Measures (PROMs) for spine was 22.14, 31.46 for hand, 24.56 for sports, and 26.81 for arthroplasty candidates. The mean score for the patient’s understanding of condition and treatment for spine was 1.9 for spine, 2.36 for hand, 2.38 for sports, and 2.38 for arthroplasty candidates. Sex and the PROMs did not show correlation. There was a correlation between increasing BMI and decreasing PROMs for spine patients. However, there was no significant correlation between BMI and the PROMs of the other musculoskeletal conditions. The spine cohort exhibited the least understanding of their condition and treatment, suggesting a correlation between a patient’s health literacy and his or her overall PROMs. Health literacy did not correlate with English as a second language (ESL). The spine cohort demonstrated the lowest PROMs while the hand cohort had the highest PROMs. Conclusion: This is the first study to make use of the MSK-HQ in an urban setting within the United States. The unique clinical characteristics within this urban population include a mean BMI of obesity, as well as a large percentage of patients with English as a second language and low health literacy. The cohort of individuals that had the worst PROM were those treated for spine conditions, while patients treated for hand and upper extremity conditions had the best PROMs. A possible explanation for this finding is increased BMI within the spine cohort, as well as decrease in patient reported understanding of condition and current treatment. Additionally, as a translator was used for each patient who indicated ESL, there was no correlation found between health literacy, total score and ESL.

POS1269 THE UTILITY OF ULTRASOUND TO PREDICT PATIENT OUTCOMES IN SHOULDER PAIN: A PROSPECTIVE OBSERVATIONAL STUDY OF 500 PATIENTS

Background:Shoulder pain is common and persistent, with a large socioeconomic burden. Ultrasound (US) scans are used for diagnosing and managing shoulder pain, but the extent to which it informs management and improves outcomes is unknown. A recent retrospective study identified groups with different patterns of US pathologies.Objectives:To confirm the existence of US-based groups of shoulder pain and determine if US-detected pathology (grouped or individual) predicts outcomes in the context of usual care. Response to local steroid injection was also evaluated.Methods:This was a 6 month, prospective, single centred, community based, observational cohort study. Inclusion: shoulder pain, ≥18 years, first shoulder US. Exclusion: shoulder surgery, inflammatory arthritis, steroid/physiotherapy in prior 6 weeks. Standardised reporting for 10 US pathologies was employed. Latent class analysis (LCA) identified pathology-based groups. Multiple linear regression analysis explored associations between baseline pathologies, subsequent treatment and 6-month Shoulder Pain and Disability Index (SPADI). Growth mixture modelling (GMM) identified groups with common trajectories of change.Results:Of 500 patients (mean age 53.6; 52% female), 330 completed follow-up. LCA identified 4 groups: bursitis without acromioclavicular joint degeneration (ACJD) (group 1), bursitis with ACJD (group 2), rotator cuff tear (group 3), no bursitis/tear (group 4). SPADI was higher at baseline for tears (55.1 vs. 49.7-51.3) (overall p=0.005), but groups did not differ at 6 months (p=0.379) (Table 1). No individual pathologies predicted 6-month outcomes. Response to baseline injection at week 2 did not differ between groups (p=0.423). GMM found 4 trajectories; the majority of patients followed trajectory 1 (little change), irrespective of US pathology group (79%, 77%, 87%, 70% of US groups 1-4 respectively) (Figure 1).Conclusion:This is the largest prospective study involving US of symptomatic shoulders, and the first to investigate groups with distinct patterns of US pathologies in predicting outcome. US-based classification of pathology (as groups or individually) did not predict 6-month outcomes with current treatments and there were no differences in short-term response to steroids between groups. The role of routine diagnostic US for shoulder pain needs consideration; it may be useful if evidence-based therapies for specific pathologies are established.Table 1.Predictors of SPADI score at 6 monthsBaseline characteristicCoefficient* (95% CI), p-valuePathology group:Bursitis w/o ACJ degeneration (group 1)ReferenceBursitis with ACJ degeneration (group 2)0.08 (-5.15, 5.32), p=0.975RC tear (group 3)5.01 (-1.48, 11.50), p=0.130No bursitis, no RC tear (group 4)1.98 (-4.00, 7.96), p=0.516Injection at scan4.87 (0.40, 9.34), p=0.033Age, years-0.01 (-0.17, 0.15), p=0.898Female-1.51 (-5.42, 2.40), p=0.448Symptom duration, months0.00 (-0.04, 0.05), p=0.879Uses arms to rise from chair2.65 (-1.50, 6.81), p=0.210Physiotherapy before baseline-0.23 (-4.78, 4.31), p=0.9201 injection before baseline2.35 (-2.87, 7.56), p=0.377≥2 injections before baseline6.53 (-2.50, 15.57), p=0.156Total SPADI0.62 (0.35, 0.89), p&lt;0.001Shoulder activity score-0.59 (-1.15, -0.04), p=0.037P-SEQ score-0.20 (-0.46, 0.07), p=0.141Brief IPQ score0.19 (-0.16, 0.54), p=0.298HADS score0.01 (-0.38, 0.41), p=0.947Constant**35.44 (29.50, 41.38), p&lt;0.001*Interpreted as unit difference in Rasch-transformed SPADI score per 1 additional unit of the independent variable **Estimated SPADI at 26 weeks in patients in the reference category for all categorical variables and with mean values for continuous covariates. ACJ=acromioclavicular joint; HADS=hospital anxiety and depression scale; IPQ=illness perception questionnaire; P-SEQ=pain self-efficacy questionnaire; RC=rotator cuff; SPADI=shoulder pain and disability indexFigure 1.Trajectories of total SPADI over time by the pathology groups found and response to injectionsAcknowledgements:This research was funded by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC) and by a NIHR Doctoral Research Fellowship (GT; DRF-2016-09-159). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. This study was also part-funded through the Arthritis Research UK Leeds Experimental Osteoarthritis Treatment Centre (20083).Disclosure of Interests:None declared

OP0278-PARE PROVIDING SUPPORT TO FAMILIES OF CHILDREN NEWLY-DIAGNOSED WITH CHILDHOOD ARTHRITIS: A PATIENT AND PARENT-LED PILOT STUDY TO DEVELOP AND ASSESS ‘A LITTLE BOX OF HOPE’ SUPPORT PACKS

Background:Juvenile Idiopathic Arthritis (JIA) is a heterogenous group of autoimmune disorders characterised by chronic joint inflammation, diagnosed in around 1 in 1,000 children and young people (CYP) under the age of 16. Delays in diagnosis are common [1], awareness is low, and paediatric rheumatological conditions have a considerable impact on young people and their families [2]. A lack of understanding amongst families of newly-diagnosed children leads to uncertainty and anxiety.Objectives:This patient and parent-led project developed a resource pack for parents of CYP newly-diagnosed with JIA, to provide information and support. Following a pilot, feedback from recipients was collated and analysed to help improve future provision.Methods:A young person with JIA identified the need for direct family support. Juvenile Arthritis Research (a UK charity) developed a unique pack of support information, containing resources for both children and their families - called A Little Box Of Hope. This included information about JIA and support services available for families, as well as Kipo (a children’s book about JIA) and accompanying finger puppet. Clinicians at one paediatric rheumatology centre provided information about the packs to newly diagnosed families, who then requested a free box to be posted to them.Following an initial pilot study, recipients were invited to complete a short online questionnaire and provide feedback to allow refinement of the provision.Results:Respondents were asked a series of questions, each on a scale of 1-5. Every respondent gave a score of 5 in response to “What do you think of the idea of A Little Box Of Hope?”Every parent of children under ten years old gave a score of 5 for every item when asked “How useful is each item in your Little Box Of Hope?”Respondents also gave free-text comments:* “It was very well thought out and I felt supported”* “I know so much more about JIA now than I did before. I cannot thank you enough.”* “It was extremely useful and made me feel supported during a very stressful time and this enabled me to support my son more effectively.”* “It made my daughter feel less alone.”Some parents of older children felt that some information specifically for teens would be useful, and a Teen pack is being developed.Conclusion:Recipients of A Little Box Of Hope have found the information useful and feel supported. Following the pilot study, we have developed My JIA, a booklet reviewed by a multi-disciplinary clinical team, with comprehensive information for families affected by JIA. A Teen pack, for children aged around 10 years or older, is being developed to provide targeted support to this group.The COVID-19 pandemic has adversely affected access to healthcare services, increasing the need for remote parent- and charity-provided support through A Little Box Of Hope.As such, we intend to expedite the roll-out of the project across the country building on the success of the pilot project.

POS0267-HPR IDENTIFYING MEANINGFUL AND DETECTABLE CHANGE FROM THE PATIENT PERSPECTIVE ACROSS COMMON FATIGUE MEASURES IN RHEUMATOID ARTHRITIS

Background:Different tools are commonly used to assess fatigue in RA including single items (visual analogue (VAS), numeric rating (NRS), and Likert scales), SF-36 Vitality, and PROMIS. Evidence is needed to identify scores that reflect meaningful change to patients to interpret fatigue results in trials and for clinical care.Objectives:To use symptom-specific and RA change anchors to estimate meaningful and detectable change scores from the patient perspective across several fatigue measures.Methods:Stable RA patients (ACR/EULAR 2010 criteria) were recruited from 3 academic clinical practices across the Southern, Mid-Atlantic, and Northeastern United States. Scales were administered at 2 consecutive visits to capture PROs including fatigue. We also asked a fatigue-specific change question (How would you rate your fatigue since the last visit?). Response options were a lot better, a little better, the same, a little worse, and a lot worse. An RA disease activity change question followed a similar format. We compared mean change between visits across fatigue and RA change categories for the Fatigue NRS, Fatigue 5-point Likert (none to very severe), SF36 Vitality, and PROMIS Fatigue 4a, 7a, and 8a.Results:The sample included 282 patients with stable RA who completed questionnaires 4.6 (SD 2.4) months apart. Patients were mostly white (78%) women (82%) with RA duration of 13 (11) years. At V1, most were in CDAI LDA (57%) or MDA (30%) with 5% in REM and 8% in HDA states. Using the Fatigue change anchor, 6% were a lot better, with mean change ranging from |1-11|points across scales (Table 1); among 13% a little better, smaller changes |0.4 to 5|were reported. Across all measures score changes for meaningful and minimal improvement were numerically larger for improvement than worsening.Fatigue Change CategoriesLot Better 6%Little Better 13%Same 49%Little Worse 22%Lot Worse 10%NMeanSDNMeanSDNMeanSDNMeanSDNMeanSDFatigue 11 point NRS19-2.22.437-0.72.3137-0.51.9610.41.9261.32.1Fatigue 5-point Likert19-0.81.236-0.41.21370.00.9600.20.9270.61.2SF36 Vitality (0-100)1911.216.1364.913.71370.310.659-3.215.326-11.416.6PROMIS Fatigue 7a19-5.98.537-2.67.51380.06.462-0.36.5274.38.3PROMIS Fatigue 8a19-6.110.237-2.77.1138-0.37.1621.36.9275.611.0PROMIS Fatigue 4a19-6.89.937-3.38.2138-0.47.4601.27.2275.211.5Using the RA change categories, more people rated their RA as at least a little better compared with fatigue (28% vs. 19%, respectively) at the second visit (Table 2). Similar patterns were evident across RA change categories, though score changes associated with improvement and worsening were about half those observed using fatigue change anchors.RA Disease Activity Change CategoriesLot Better13%Little Better15%Same42%Little Worse21%Lot Worse9%NMeanSDNMeanSDNMeanSDNMeanSDNMeanSDFatigue 11 point NRS36-0.82.343-0.62.7117-0.21.958-0.21.9260.72.2Fatigue 5-point Likert35-0.31.242-0.31.11180.11.0580.10.8260.31.3SF36 Vitality (0-100)356.417.4433.813.0117-0.612.957-3.711.325-6.017.0PROMIS Fatigue 7a37-1.69.543-1.57.4118-0.37.0590.55.6261.37.5PROMIS Fatigue 8a37-2.19.543-1.79.01180.17.6590.74.8263.011.4PROMIS Fatigue 4a36-2.79.643-2.39.01180.18.1590.45.6252.612.0Conclusion:The score change associated with meaningful improvement and worsening between visits on commonly used fatigue scales was much larger with fatigue vs. RA change categories. More people rated their RA improved as compared with fatigue at the 2nd visit. Symptom-specific anchors are likely to offer more relevant change scores associated with meaningful improvement and worsening than RA change anchors. These estimates offer new information about meaningful and detectable improvement and worsening on common measures for trialists, researchers, and clinicians monitoring fatigue in people with RA.Acknowledgements:The primary research data included within this report were acquired through funding in part from a PCORI Methods Award (SC14-1402-10818). This work was also supported by the NIH through the Rheumatic Diseases Resource-based Core Center (P30-AR053503 Core D, and P30-AR070254, Core B), the Camille Julia Morgan Arthritis Research and Education Fund, and the Rheumatoid Arthritis Discovery Fund.Disclosure of Interests:None declared

Access to Care and Diagnostic Delays in Juvenile Dermatomyositis: Results From the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry.

ObjectiveTo determine factors associated with diagnostic delays and outcomes in juvenile dermatomyositis (JDM) in the Childhood Arthritis and Rheumatology Research Alliance Legacy Registry (CLR).MethodsThis was a cross‐sectional study of subjects aged 0 to 17 years with JDM enrolled to the CLR from 2010 to 2015. Access to care was measured by calculating the distance from the subject zip code of residence to the treating pediatric rheumatology center and determining the state density of pediatric rheumatologists based on the 2015 American College of Rheumatology Workforce Study. Delay was categorized as early (<30 days), typical (1‐3 months), moderate (3‐12 months), and severe (>12 months). Ordered generalized additive models were used to determine the association between these measures and diagnostic delays.ResultsThe median time to diagnosis was 3.1 months; 37.2% of patients experienced moderate delays, and 14.6% experienced severe delays. In a univariate analysis, younger age of disease onset and male sex were associated with delays. Using a generalized additive model accounting for age, sex, race, and ethnicity, increasing distance from treating pediatric rheumatologist and younger age at disease onset were associated with diagnostic delay. There was no association between the state density of rheumatologists and diagnostic delays in this model.ConclusionIn the CLR, we found moderate to severe diagnostic delays in the majority of subjects with JDM. Our data suggest that access to care, measured as the distance traveled to treating rheumatologist, is an important factor associated with delays in care but also highlight age as a contributing factor, suggesting that JDM may be less recognizable in young children.

Identifying and Validating Plasma Circulating Renin‐Angiotensin System Components as Reliable Biomarkers of Rheumatoid Arthritis

Objective The renin-angiotensin system (RAS) is an enzymatic cascade that controls the cardiovascular, renal, and adrenal functions responsible for maintaining arterial blood pressure and balancing body fluids and electrolytes. The RAS comprised of two opposing arms: i) classical arm, consists of Angiotensin (Ang) Converting Enzyme (ACE) /Ang II/ Ang II type 1 receptor (AT1R), which modulates a diverse range of biological effects, including vasoconstriction, vascular smooth muscle cell proliferation, and hypertrophy of heart vessel wall, ii) protective arm, consists of ACE2/Ang-(1-7)/Mas receptor (MasR), that acts as the counter regulatory within the RAS. Chronic imbalances of these two arms of the RAS leads to different pathophysiological conditions in renal, cardiovascular (CV), and central nervous systems. The urinary or plasma circulating level of ACE2 has been associated with different disease conditions such as renal, CV, and metabolic disorders. The plasma circulating level of ACE2 has been associated with different diseases. As a body's defense mechanism, the increased level of circulating ACE2 degrades Ang II and keeps its level within the normal range. Several studies links plasma or urinary ACE2 levels in patients with various disease. These patients exhibited reduced ACE2 activity and considerable high levels of circulating anti-ACE2 autoantibody, suggesting that an assessment of circulating ACE2, anti-ACE2, Ang II and Ang1-7 could provide a useful diagnostic biomarkers panel for patients with different inflammatory diseases. Methods This study was conducted based on an approved IRB and using twelve unidentifiable rheumatoid arthritis (RA) patients (five active and seven remission patients) samples, which were provided by the Institute of Arthritis Research. Diagnosis of RA was made using a RAPID3 questionnaire in tandem with comparing the measured amount of C-reactive protein and Vectra DA score. Levels of Ang-(1-7) and Ang II peptides were measured using liquid chromatography in tandem with mass spectrometry. Anti-ACE2 autoantibodies were measured using a previously-established ELISA method. Results The Mean ± SD results of the levels of Ang-(1-7) and Ang II peptides show that Ang-(1-7) level in the active RA group (1.29 ± 1.79) was significantly lower than in the remission RA group (7.62 ± 7.035). In contrast to Ang-(1-7), Ang II levels were significantly higher in the active RA patients (5.43 ± 4.05) when compared with the remission group (0.86 ± 0.43) (Fig.1). The mean ELISA score was significantly higher in the active RA patients (Fig.1) and was also correlated with Ang II levels in the active but not in the remission group (Fig. 2). These results suggest that anti-ACE2 antibody is associated with RA activity and intensity. Conclusion Our study suggests that estimation of the level of Ang-(1-7) and Ang II peptides in addition to assessing anti-ACE2 antibodies in patient's plasma can be considered as effective means of RA stage diagnosis. This approach also could be applied to other inflammatory conditions such as cardiovascular, renal and pulmonary diseases, diabetes and cancer.

Enhancing patient research partner engagement: Research in psoriatic arthritis.

The perspective from individuals with psoriatic arthritis (PsA) can be beneficial to PsA research, increasing the likelihood that the results are meaningful and relevant to PsA patients. While there has been an advancement of patient research partner (PRP) involvement in PsA research over time, the effort is still in its infancy. Measures to ensure PRP engagement (PRPE) occurs and its impact evaluated need to be implemented routinely to increase PRPE in PsA research.

O13 Which composite measure best reflects disease activity and predicts treatment change in psoriatic arthritis?

Abstract Background/Aims Multiple composite measures of disease activity are available and used in psoriatic arthritis (PsA) research; however, poor agreement remains amongst clinicians on the optimal measure of disease activity. Research to date has focused on polyarticular PsA, despite oligoarticular disease accounting for around half of cases in clinical practice. We aim to compare the ability of Composite Psoriatic Disease Activity Index (CPDAI), Psoriatic ArthritiS Disease Activity Score (PASDAS), Disease Activity score for PSoriatic Arthritis (DAPSA), GRAppa Composite scorE (GRACE) and Disease Activity Score 28 CRP (DAS28-CRP) to assess disease activity and predict treatment change, amongst usual care patients with oligoarticular and polyarticular psoriatic disease. Methods The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise (GRACE) dataset was utilised. Oligoarthritis was defined as &amp;lt; 5 active joints. Reference measures were clinician and patient opinions on disease control and whether treatment was escalated. Patients with baseline data for all composite measures were included. The ability of each composite measure to predict treatment change and capture disease activity was compared using the Mann-Whitney U test. Results Data were available for 271 patients (152 oligoarthritis, 119 polyarthritis). The mean age, duration of PsA and psoriasis were similar for both groups. A higher proportion of oligoarticular patients were male. Patients with polyarticular disease had higher disease activity in skin, enthesitis and dactylitis. Using both patient and physician definitions of disease control, all composite measures were able to differentiate between patients with active and quiescent disease, regardless of disease subtype (p &amp;lt; 0.05). PASDAS demonstrated the largest differentiation in score. Differences between active and inactive disease scores were more pronounced in oligoarticular disease. PASDAS demonstrated the greatest ability to predict treatment change in both oligoarticular and polyarticular disease. Interestingly, DAPSA could not predict treatment change in polyarticular patients, p = 0.074 (Table 1). Conclusion This is the first study to compare composite measures, in oligoarticular and polyarticular PsA in a multinational cohort. All composite measures of disease activity were able to differentiate between active and inactive disease in both subtypes. PASDAS demonstrated the largest discrimination in both polyarticular and oligoarticular disease, suggesting greatest clinical and research utility. Disclosure L. Tucker: None. P. Helliwell: None. L. Coates: None.

Survey of current practices in the management of anti-TNF failure in juvenile spondyloarthritis

To evaluate the current practices in management of patients with juvenile spondyloarthritis (JSpA) who failed anti-tumour necrosis factor agents (anti-TNF). An online survey was distributed to Childhood Arthritis and Rheumatology Research Alliance (CARRA) members of the JIA workgroup. Data collection included estimated number of JSpA patients who have failed anti-TNF therapy over two-year period, reasons for discontinuing anti-TNF therapy and other medications used afterward. The JSpA population was de ned as the following subtypes: enthesitis-related arthritis, psoriatic arthritis, undifferentiated spondyloarthritis, juvenile ankylosing spondylitis (AS) i.e. meeting modi ed NY criteria for AS before age 16, and reactive arthritis. Findings were summarised using descriptive statistics. The survey response rate was 36% (n= 60/169). The majority of participants were paediatric rheumatologists (93%). Many physicians have JSpA patients who failed anti-TNF therapy (63%). The most common reason for changing anti-TNF therapy was secondary non-response (72%). Sacroiliitis was the most important factor considered when assessing response to an anti-TNF agent and the most common reason for primary non-response (45%). When assessing anti-TNF failure for sacroiliitis, many (65%) felt imaging of the sacroiliac joints was the most important aspect in their decision making. The majority try a second anti-TNF agent after initial anti-TNF failure (87%) and switch to another medication class after 2 anti-TNF agents have failed (62%). More than half of paediatric rheumatologists surveyed have at least one JSpA patient who failed anti-TNF therapy. The majority failed because of secondary non-response. Sacroiliitis is an important but challenging aspect to manage for patients with JSpA.