O043 / #45 Topic: AS05 - CNS Lupus ABSTRACT CONCURRENT SESSION 07: COGNITION IMPAIRMENT IN SLE – RECENT ADVANCEMENT AND EMERGING RESEARCH 23-05-2025 1:40 PM - 2:40 PM Cognitive impairment (CI) is frequently observed in systemic lupus erythematosus (SLE) and negatively affects health-related quality of life. Despite increased research in this field, there remains a lack of multicentered studies and external validation of findings between centers. This abstract summarizes the first international, multicenter meeting to discuss the harmonization of research into CI in SLE. The aims of the meeting were to identify the current challenges in this field, knowledge gaps and opportunities to harmonize research across centers. Thirty-seven interdisciplinary researchers (pediatric and adult rheumatologists, psychiatrists, psychologists, physicists, engineers) from 12 centers across 6 countries were invited. Researchers were selected based on having an established publication record in the field of CI in SLE. During the meeting 2 breakout groups were created, one focused on clinical/psychological aspects and the other on neuroimaging. Key topics to discuss were prepared in advance, based on gaps in the current literature and areas that needed further understanding and consistency in research design. These included: core datasets needed for CI in SLE research, current cognitive measures used, weaknesses of these measures, differences between pediatric and adult CI, subjective vs objective CI, current neuroimaging in CI and gaps in the field. In terms of a core dataset there was a ‘long-list’ of factors discussed (Table 1). This was not a definitive list but a starting point for additional work required to determine priorities and core factors to consider in CI research. Instead of the American College of Rheumatology neuropsychological battery, identifying specific cognitive domains pertinent to patients with SLE was proposed. This proposed change would help overcome previous test limitations such as validation of tests in alternative languages and in a pediatric population. When considering the new domains, we also need to establish the purpose of the tool, for clinical or research. This setting would then also affect whether we need screening or in-depth measures. Measurements of both objective and subjective CI were considered important, as well as ecologically valid measures to capture cognitive performance in everyday life and measures of resilience. It was agreed that current CI measures account for some potential confounders (eg, age and sex), but other important factors are overlooked, such as social determinants of health. The use of normative data can help with some confounders but regression-based norms maybe more useful. The neuroimaging breakout group identified 10 acquisition methods in current use, with the majority collecting T1 structural, diffusion weighted imaging and resting state functional MRI. The group also identified 15 different types of software that are in use in the analysis stage (Table 2). Discussions included use of the “traveling head” methodology for multicentered studies, and the use of software algorithms in artificial intelligence to computationally harmonize some scans. Overall, in terms of harmonizing imaging research across institutes 4 areas were targeted: scanner features and location, and participant, acquisition protocol, and analytic pipeline harmonization. Table 1: A list of some factors assessed when conducting CI in SLE research Table 2: Imaging data acquisition methods and software currently used by symposium attendees Studying CI in SLE is complex and is complicated further by its multifactorial nature and confounders. Minimizing variation by harmonizing research methods, especially clinical and imaging data acquisition and analysis across centers, is an important step to advancing knowledge of CI in the diverse population that is SLE patients. A wider international group will move forward with harmonization efforts and development of a finalized core dataset. Acknowledgment: FAPESP grant 22/00597-6.

OBJECTIVE:SLE is a complex, heterogenous autoimmune disease. SLE researchers do not always collect the same data, making comparative studies difficult. We aimed to ascertain what variables SLE clinical researchers commonly collect for SLE research. Our ultimate goal is to generate a minimal core dataset for future SLE studies. METHODS:In 2020, we designed and distributed a questionnaire to members of the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) as well as additional active research centres in China. Our survey included 26 questions about the types of data that are routinely collected for research. Variables collected by ≥75% of participating respondents were used as a threshold for inclusion. RESULTS:18 of 36 invited respondents replied (8 from USA/Canada, 5 from China and 5 from Europe). Many key variables in the domains of sociodemographics, SLE specific, comorbidities, baseline haematology/biochemistry/immunology and treatment data were collected by ≥75% respondents including the 1997 American College of Rheumatology (ACR) Classification Criteria (83%), SLE Disease Activity Index-2000 (82%), current treatment (100%), drug name, dose, frequency and start date (75-100%) and complement C3/4 (94%). A range of other items was collected by 50-<75% of respondents including SLICC 2012 Criteria (67%), SLICC/ACR Damage Index (68%) and Short Form Health Survey-36 (53%). Less than 50% of respondents collect certain items including European Alliance of Associations for Rheumatology/ACR 2019 criteria (33%), British Isles Lupus Assessment Group scores (12%) and pneumococcal vaccine status (39%). CONCLUSIONS:The frequency with which an initial set of variables is collected in SLE cohorts globally was identified and can form the basis from which to develop a core minimum dataset for SLE. Further refinement and common definitions will be needed to finalise a minimal core dataset suitable for widespread use.

O066 / #230 Topic: AS21 - Pregnancy and Reproductive Health ABSTRACT CONCURRENT SESSION 11: PREGNANCY IN SLE 24-05-2025 10:40 AM - 11:40 AM High maternal body mass index (BMI) is a well-established modifiable risk factor for adverse pregnancy outcomes (APO) in the general obstetric population. Best practices recommend appropriate prepregnancy weight management to optimize outcomes. However, the prevalence of obesity and its impact in systemic lupus erythematosus (SLE) pregnancies are poorly understood, despite the higher APO risk in SLE. We evaluated baseline BMI in a prospective SLE pregnancy cohort to determine if overweight (25-29.9 kg/m²) or obese (≥30 kg/m²) BMI conferred higher APO risk compared to BMI < 25 kg/m2. We enrolled pregnant SLE women at <17 weeks gestation at Systemic Lupus International Collaborating Clinics (SLICC) centers in Canada (Montreal, Quebec City, Calgary, Halifax) and South Korea (Seoul). We collected data on demographics, obstetrical history, SLE characteristics, baseline comorbidities, and APO at each of the 2nd trimester, 3rd trimester, and end-of-pregnancy visits (8-12 weeks after end of pregnancy). APO included 1) fetal death >20 weeks gestation, 2) neonatal death due to preterm birth and/or placental insufficiency, 3) preterm delivery or termination < 36 weeks due to placental insufficiency, gestational hypertension, preeclampsia, and/or eclampsia, and 4) small for gestational age (SGA; < 5th percentile). We assessed the proportion of APO across the different BMI groups. We conducted a multivariate analysis using the Korean BMI classification for pregnancies from Asian mothers, categorizing BMI as follows: obese (BMI ≥25), overweight (BMI 23-24.9), and normal weight (BMI < 23). We analyzed 80 completed pregnancies, with a mean maternal age of 33.9 years (standard deviation, SD 4.1) and a mean maternal BMI of 26.0 kg/m2 (SD 6.7). Almost half (40%) of pregnancies had a maternal BMI ≥25 kg/m2. Non-Hispanic Whites made up 40% of the pregnancies and more than half (56%) of pregnancies with a maternal BMI ≥30 kg/m2 (Table 1). Aspirin use was more common in the BMI ≥30 kg/m2 group, while steroids were more frequently used in pregnancies with BMI < 25 kg/m2. Overall, APO occurred in 8 (10%) pregnancies (Table 2). The proportion of APO was 19% [95% confidence interval (CI) 0, 38%] in both the BMI 25-29.9 kg/m2 and BMI ≥30 kg/m2 groups and 4% (95% CI 1, 12%) in the BMI < 25 kg/m2 group. In univariate analysis, there was more than a 5-fold increased risk of APO in pregnancies with maternal BMI ≥25 kg/m2 vs those with BMI < 25 kg/m2 [odds ratio (OR) 5.31; 95% CI 1.00, 28.24]. In multivariate analysis, using the Korean BMI classification for all Asian mothers, as well as adjusting for race and antiphospholipid antibody status, overweight and obese pregnancies had a substantially increased risk of APO compared to those with normal weight (OR 6.32; 95% CI 1.25, 32.0). Table 1. SLE Pregnancy Characteristics by Body Mass Index (BMI, kg/m2) Table 2. Pregnancies with Adverse Outcomes by Body Mass Index (BMI, kg/m^2) Overweight and obese SLE women had a higher risk of APO compared to the normal weight group. High BMI may be a modifiable risk factor for APO in women with SLE. Preconception weight interventions may improve outcomes in SLE pregnancies.

Objective To evaluate the effect of an educational tool on preeclampsia knowledge, as well as aspirin (ASA) use and adherence in pregnant SLE women.Methods A two-arm parallel randomized controlled trial was conducted recruiting pregnant SLE women up to 17 weeks' gestation. Participants were randomly assigned to receive either usual-care alone or usual-care plus the tool (laminated card incorporating infographics on preeclampsia in SLE and ASA for prevention). The primary outcome was difference in preeclampsia knowledge scores at the second-trimester visit.Results Of 73 women included, 38 were randomized to the intervention. In the primary analysis of ongoing pregnancies, increase in the mean preeclampsia knowledge scores was 4.0 points (95% CI: 2.4, 5.6) in the intervention group and 2.0 points (95% CI: 0.3, 3.9) in controls, with a mean difference of 1.8 points higher (95% CI: -0.5, 4.2) favouring the intervention. Including end-of-pregnancy scores of women with fetal loss (six in each group), the difference was 4.8 points (95% CI: 3.3, 6.9) in the intervention group and 1.9 points (95% CI: 0.3, 3.6) in controls, with a mean increase of 2.5 points (95% CI: 0.3, 4.8) more for the intervention. Using electronic pharmacy data, there was a trend for higher ASA adherence in the intervention group (81%) vs controls (65%; difference 15%, 95% CI: -9, 37%).Conclusion Women with SLE who received an educational tool had greater improvement in preeclampsia knowledge vs controls. This tool may improve ASA use in SLE pregnancies and help optimize outcomes.Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT03749044.

Economic analyses of SLE often include only direct healthcare costs. Indirect costs, particularly from lost productivity in unpaid labor, are often overlooked, especially relevant for a disease disproportionately affecting women. We assessed indirect costs due to lost productivity in both paid and unpaid labor, stratified by gender, in a national multicenter SLE cohort. Patients fulfilling ACR or SLICC SLE Classification Criteria completed a validated questionnaire on lost productivity. Total indirect costs included: 1) absenteeism (time lost from paid labor because of illness), 2) presenteeism (degree of productivity impairment in paid/unpaid labor), 3) opportunity costs (additional time patients would be working in paid/unpaid labor if not ill). Opportunity costs were calculated as the difference between the time patients worked versus an age, sex, and geographic-matched general population in paid and unpaid labor. Indirect costs from paid and unpaid labor were valued using age-and-sex-specific wages from Statistics Canada. The association of gender with annual indirect costs was assessed (adjusted for race/ethnicity, age, disease duration, and the SLICC/ACR Damage Index [SDI]) using random effects linear regression modeling. 1804 patients participated, 90.8% female, 66.9% white, mean age at diagnosis 33.7 (SD 13.9) years, mean SLE duration 14.7 (11.7) years, and mean SDI 1.3 (range 0-12.0). Patients were followed a mean of 4.9 (range 1.0-9.6) years with 48.9% employed (49.5% among females, 44.0% among males) at the initial and 37.0% (37.1% among females, 36.7% among males) at the final observation. Overall, total annual indirect costs were $36 405 (absenteeism: $829; presenteeism in paid labor: $4624; presenteeism in unpaid labor: $8922; opportunity costs in paid labor: $8512; opportunity costs in unpaid labor: $13 519). Among women, opportunity costs from unpaid labor were 38.8% ($14 175/$36 538) and from paid labor 21.3% ($7802/$36 538) of total indirect costs; among men, opportunity costs from unpaid labor were 19.3% ($6765/$35 064) and from paid labor 44.7% ($15 685/$35 064) of total indirect costs (Figure 1). Regression modeling showed that women incurred higher opportunity costs from unpaid labor (coefficient $7309, 95% CI $3514, $11 105), and lower opportunity costs from paid labor (coefficient −$8336, 95% CI −$12 524, −$4147). Figure 1a: Components of Annual Indirect Costs: Female Total: $36 538 (2023 Canadian Dollars) Figure 1b: Components of Annual Indirect Costs: Male Total: $35 064 (2023 Canadian Dollars) Indirect costs, particularly from unpaid labor, are substantial, especially in women, where they represent 38.8% of total indirect costs versus 19.3% in men. Hence, economic analyses weighing costs and benefits of novel/emerging therapies should incorporate costs resulting from lost productivity, particularly important for a disease that disproportionately affects women.

O052 / #245 Topic:AS24 - SLE-Treatment ABSTRACT CONCURRENT SESSION 09: SLE THERAPY – REVISITING OLD DRUGS AND UNLOCKING HIDDEN POTENTIAL OF NEW MEDICATIONS 24-05-2025 10:40 AM - 11:40 AM We previously evaluated hydroxychloroquine (HCQ) tapering/cessation and risk of systemic lupus erythematosus (SLE) flare in the SLICC Inception cohort. However, in our approach we did not account for potential bias due to interval-censored (IC) outcomes, where exact timing of events are unknown. Our objective was to address this, with alternative approaches to defining timing of IC events, including the Simulation Extrapolation (SIMEX) approach. We evaluated 1,543 members of the SLICC Inception cohort (January 1999 to January 2019). Adults (18+) with SLE were enrolled in this cohort within 15 months of diagnosis and followed annually with questionnaires and physician assessment. In our time-to-event analyses, time-zero was defined as cohort entry if a subject was taking HCQ at the time, or the first prescription of HCQ otherwise. HCQ tapering/cessation was defined as the first cessation or decreased dose of HCQ and modeled as a binary time-varying exposure. Multivariable proportional hazard regression assessed associations between HCQ tapering/cessation and time to SLE flare, controlling for demographics (age, sex, race/ethnicity, region, education), baseline medication (steroids, immunosuppressives, biologics), enrollment year, time between diagnosis and cohort entry, smoking status, end-stage renal disease, and body mass index. Lupus flare was defined as the earliest of: A. Increase (from prior score) of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), B. Increase/initiation of SLE therapy (prednisone, immunosuppressive, or biologic), or C. SLE-related hospitalization. Since exact date of increased SLEDAI-2K was unknown, these represented IC events. We compared alternative analyses, imputing the IC event time at either the end- or the mid-point of the interval between the previous clinic visit and the visit when the outcome was reported. In sensitivity analyses we used SIMEX, a more sophisticated method based on simulations that allowed us to assess how the HR of interest changes with increasing time interval between adjacent visits. By extrapolating observed trends between the original and simulated data, we could correct the bias estimated to be within the original data, due to IC events.[1] Out of the total 1,543 subjects, 398 (25.8%) decreased or stopped their HCQ at some point during their follow-up and 1,187 experienced a disease flare (76.9%). When IC event times were imputed at the end of the relevant time interval, the adjusted HR for flare related to HCQ decrease/cessation was 1.43 (95% confidence interval, CI 1.24-1.66). When IC event times were imputed at the mid-point, the point estimate for the adjusted HR was slightly higher (1.53, 95% CI1.32-1.78). SIMEX correction yielded an even higher point estimate for the adjusted HR (1.68, bootstrapped 95% CI 1.44-2.02). HCQ tapering/cessation was associated with greater flare risk regardless of how IC events were handled. Correcting imprecise timing of IC events tended to increase the strength of estimated associations, although confidence intervals overlapped. Limitations of these analyses include failure to account for disease status and/or other concomitant drug changes at tapering/cessation. Future analyses will address these issues (and stratify outcomes according to whether HCQ was tapered vs stopped).References:[1.] Abrahamowicz M. Biom J 2022;64(8):1467-85.

O030 / #400 Topic: AS23 - SLE-Diagnosis, Manifestations, & Outcomes ABSTRACT CONCURRENT SESSION 05: EMERGING INSIGHTS ON THE MANAGEMENT OF LUPUS MANIFESTATIONS AND COMORBIDITIES 23-05-2025 1:40 PM - 2:40 PM We described the direct healthcare costs associated with damage accrual in patients in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort.[1] However, our estimates only included partial direct costs and indirect costs from lost productivity were not included. We supplemented our primary data by querying a cohort subset on all healthcare use and lost time in paid/unpaid labor and provide estimates of complete direct and indirect costs for the full cohort, stratified by damage. Between 1999 and 2011, SLE patients from 31 centers in 10 countries were enrolled into the SLICC Inception Cohort within 15 months of diagnosis and data on disease damage (SLICC/ACR Damage Index [SDI]) and limited healthcare use (ie, hospitalizations, medications, and dialysis) were collected annually through to July 2022. Starting in 2015, 18 sites collected supplemental economic data annually (ie, visits to physicians, nonphysician healthcare professionals, and the emergency room, laboratory tests, radiological/other diagnostic procedures, outpatient surgeries, help obtaining medical care, and lost time in paid/unpaid labor). Direct costs were calculated by multiplying each health resource by its corresponding 2023 Canadian unit cost. Total indirect costs included: 1) absenteeism (time lost from paid labor because of illness), 2) presenteeism (degree of patient self-reported productivity impairment in paid/unpaid labor, based on a visual analog scale), and 3) opportunity costs (additional time patients would be working in paid/unpaid labor if not ill). Opportunity costs were calculated as the difference between the time patients reported working vs that worked by an age, sex, and geographic-matched general population in paid/unpaid labor. Indirect costs from paid/unpaid labor were valued using age-and-sex-specific wages from Statistics Canada. Multiple imputation was used to predict missing cost values for the patients in the full cohort who provided only utilization data for hospitalizations, medications, and dialysis for all observations. At each assessment, patients were assigned to one of 6 damage states (ie, SDI = 0, 1, 2, 3, 4, ≥ 5) and annual costs, both unimputed and including imputations, were stratified by SDI score. Means and 95% confidence intervals were computed and compared. 1694 patients (88.8% female, 48.9% White, mean age at diagnosis 34.6 years, mean disease duration at cohort enrollment 0.5 years), were followed for a mean of 10.5 (SD 5.3) years. Of these 1694 patients, 766 (89.7% female, 41.4% White, mean age at diagnosis 33.0 years, mean disease duration at cohort enrollment 0.4 years) completed the supplemental economic questionnaire. Their mean disease duration at the time of introduction of the supplemental questionnaire was 10.9 (range 3.9-19.5) years and this cohort subset provided this additional economic data for a mean of 3.5 (SD 1.9) years. Among the cohort subset completing the supplemental economic questionnaire, on average, indirect costs, primarily from unpaid labor, accounted for 81.1% of total costs (Table 1). For the full cohort, annual direct and indirect costs increased with increasing SDI (SDI=0: total costs $33,812 [95% CI $31,088, $36,537]; SDI ≥ 5: total costs $90,839 [95% CI $82,275, $99,403]) (Table 2). Table 1. Annual complete direct, indirect, and total costs (in 2023 Canadian dollars) for the cohort subset providing complete cost data, stratified by SDI (n = 2414 observations). Values are means. Table 2. Annual imputed complete direct, indirect, and total costs (in 2023 Canadian dollars) for the full cohort, stratified by SDI (n = 15,106 observations). Patients with the highest vs the lowest SDIs incurred complete direct costs that were 5.9-fold higher and indirect costs 2.1-fold higher. However, patients with no or minimal damage still experienced considerably reduced productivity. Indirect costs exceeded direct, on average, by 4.5-fold, underscoring the importance of incorporating lost productivity in estimating the economic burden of SLE. References: [1.] Barber MRW. Arthritis Care Res 2020;72:1800-8.

To determine if overweight (25-29.9 kg/m2) or obese (≥30 kg/m2) baseline body mass index (BMI) conferred higher adverse pregnancy outcomes (APO) risk compared to BMI <25 kg/m2 in a prospective systemic lupus erythematosus (SLE) pregnancy cohort. We enrolled pregnant SLE women at <17 weeks gestation at 5 Systemic Lupus International Collaborating Clinics centers in Canada and South Korea. We collected data on demographics, obstetrical history, SLE characteristics, baseline comorbidities, and APO at each of the 2nd trimester, 3rd trimester, and end-of-pregnancy (8-12 weeks) visits. APO included: (1) fetal death >20 weeks’ gestation, (2) neonatal death due to preterm birth and/or placental insufficiency, (3) preterm delivery or termination <36 weeks due to placental insufficiency, gestational hypertension, preeclampsia, and/or eclampsia, and (4) small for gestational age (<5th percentile). We assessed the proportion of APO across the different BMI groups. We conducted a multivariate analysis using the Korean BMI classification for pregnancies from Asian mothers [obese (BMI ≥25 kg/m2), overweight (BMI 23-24.9 kg/m2), and normal weight (BMI <23 kg/m2)]. We analyzed 80 completed pregnancies, with a mean maternal age of 33.9 years (standard deviation, SD 4.1) and BMI of 26.0 kg/m2 (SD 6.7). Almost half (40%) of pregnancies had a maternal BMI ≥25 kg/m2. Non-Hispanic Whites made up 40% of the pregnancies and more than half (56%) of pregnancies with a maternal BMI ≥30 kg/m2 (Table 1). Overall, APO occurred in 8 (10%) pregnancies. The proportion of APO was 19% [95% CI 0, 38%] in both the BMI 25-29.9 kg/m2 and BMI ≥30 kg/m2 groups and 4% (95% CI 1, 12%) in the BMI <25 kg/m2 group. In univariate analysis, there was more than a 5-fold increased risk of APO in pregnancies with maternal BMI ≥25 kg/m2 versus those with BMI <25 kg/m2 [odds ratio (OR) 5.31; 95% CI 1.00, 28.24]. In multivariate analysis, using the Korean BMI classification for all Asian mothers and adjusting for race and antiphospholipid antibody status, overweight and obese pregnancies had a substantially increased risk of APO compared to those with normal weight (OR 6.32; 95% CI 1.25, 32.0). Table 1. SLE Pregnancy Characteristics by Body Mass Index (BMI, kg/m 2 ) Overweight and obese SLE women had higher APO risk compared to those with normal weight. High BMI may be a modifiable risk factor for APO in women with SLE. Supported by a CIORA grant

ObjectivesThis study aims to determine the independent impact of definitions of remission/low disease activity (LDA) on direct/indirect costs (DCs, ICs) in a multicentre inception cohort.MethodsPatients from 31 centres in 10 countries were enrolled within 15 months of diagnosis and assessed annually. Five mutually exclusive disease activity states (DAS) were defined as (1) remission off-treatment: clinical (c) SLEDAI-2K=0, without prednisone/immunosuppressants; (2) remission on-treatment: cSLEDAI-2K=0, prednisone ≤5 mg/day and/or maintenance immunosuppressants; (3) LDA-Toronto Cohort (TC): cSLEDAI-2K≤2, without prednisone/immunosuppressants; (4) modified lupus LDA state (mLLDAS): SLEDAI-2K≤4, no activity in major organs/systems, no new activity, prednisone ≤7.5 mg/day and/or maintenance immunosuppressants and (5) active: all remaining assessments.At each assessment, patients were stratified into the most stringent DAS fulfilled and the proportion of time in a DAS since cohort entry was determined. Annual DCs/ICs (2021 Canadian dollars) were based on healthcare use and lost workforce/non-workforce productivity over the preceding year.The association between the proportion of time in a DAS and annual DC/IC was examined through multivariable random-effects linear regressions.Results1692 patients were followed a mean of 9.7 years; 49.0% of assessments were active. Remission/LDA (per 25% increase in time in a remission/LDA state vs active) were associated with lower annual DC/IC: remission off-treatment (DC −$C1372; IC −$C2507), remission on-treatment (DC −$C973; IC −$C2604,) LDA-TC (DC −$C1158) and mLLDAS (DC −$C1040). There were no cost differences between remission/LDA states.ConclusionsOur data suggest that systemic lupus erythematosus patients who achieve remission, both off and on-therapy, and reductions in disease activity incur lower costs than those experiencing persistent disease activity.

ObjectiveGiven global shortages in the rheumatology workforce, the demand for rheumatology assessment often exceeds the capacity to provide timely access to care. Accurate triage of patient referrals is important to ensure appropriate utilization of finite resources. We assessed the feasibility of physiotherapist (PT)-led triage using a standardized protocol in identifying cases of inflammatory arthritis (IA), as compared to usual rheumatologist triage of referrals for joint pain, in a tertiary care rheumatology clinic.MethodsWe performed a single-center, prospective, nonblinded, randomized, parallel-group feasibility study with referrals randomized in a 1:1 ratio to either PT-led vs usual rheumatologist triage. Standardized information was collected at referral receipt, triage, and clinic visit. Rheumatologist diagnosis was considered the gold standard for diagnosis of IA.ResultsOne hundred two referrals were randomized to the PT-led triage arm and 101 to the rheumatologist arm. In the PT-led arm, 65% of referrals triaged as urgent were confirmed to have IA vs 60% in the rheumatologist arm (P= 0.57), suggesting similar accuracy in identifying IA. More referrals were declined in the PT-led triage arm (24 vs 8,P= 0.002), resulting in fewer referrals triaged as semiurgent (6 vs 23,P= 0.003). One case of IA (rheumatologist arm) was incorrectly triaged, resulting in significant delay in time to first assessment.ConclusionPT-led triage was feasible, appeared as reliable as rheumatologist triage of referrals for joint pain, and led to significantly fewer patients requiring in-clinic visits. This has implications for waitlist management and optimal rheumatology resource utilization.

ObjectiveAntigen-presenting dendritic cells (DCs) and monocytes play an essential role in rheumatoid arthritis (RA) pathogenesis, however, their tolerogenic potential remains unclear. Herein, the tolerogenic profiles of DCs are characterized in treatment-naïve RA patients to determine their role to inflammatory arthritis management.MethodsThirty-six treatment-naïve RA patients were enrolled, of which 62% were non-responders to methotrexate (MTX) monotherapy based on disease activity score (DAS) after 6-months of therapy. DC and monocyte subset frequencies, activation (CD40, CD86, CD209 expression), and tolerogenic profile (intracellular indoleamine-2,3-dioxygenase [IDO1] and cytotoxic T lymphocyte antigen 4 [CTLA-4] expression) were examined in the baseline peripheral blood by multicolor flow-cytometry. Soluble CTLA-4 (sCTLA-4) levels in plasma were measured.ResultsDC subsets were decreased in RA compared to healthy controls (HC), and the frequency of conventional DCs (cDC) inversely correlated with inflammatory markers and improvement in disease activity. CD141+ cDC1s were the major IDO1-expressing cells. IDO1+cDC1s were reduced in RA patients compared to HC. The baseline frequency of IDO1+cDC1s inversely correlated with improvement in disease activity. CTLA-4 expression in CD1c+ cDC2s and monocytes was lower in RA patients compared to HC. Moreover, MTX-responders had a significantly lower frequency of IDO1+cDC1 cells and higher level of sCTLA-4 in the plasma compared to MTX non-responders. There was a strong predictive association of low IDO1+cDC1 cells, low sCTLA-4 and non-response to MTX.ConclusionsOur findings reveal altered DC and monocytes immunophenotypes that are associated with RA pathology and treatment response. The frequencies of tolerogenic IDO1+cDC1s and the low level of sCTLA-4 are strongly associated with MTX non-responsiveness and therapeutic outcome. These results suggest that investigation of the association IDO1+cDC1 and sCTLA-4 with response to treatment may be more generalizable to other autoimmune diseases.

OBJECTIVES:The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptoms severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. METHODS:This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. RESULTS:The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, P = 0.04). Age at diagnosis and focal central events emerged as additional response predictors. CONCLUSION:NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Introduction Loneliness is prevalent among patients with inflammatory rheumatic diseases (IRDs), however the COVID-19 pandemic may intensify loneliness among patients with IRDs, as they are at higher risk of severe illness. Early evidence suggests that this was indeed the case during the early stages; however, it remains largely unknown whether loneliness remains present and what factors are associated. The objective of the present study was to identify risk and protective factors associated with loneliness in individuals living with IRDs in the later stage of the COVID-19 pandemic. Methods Data from an online cross-sectional survey study of individuals with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) between May 2022 and February 2023. Participants were recruited from a list of patients already enrolled in a multi-site longitudinal observation study. All participants provided informed consent. Loneliness was assessed with the University of California, Los Angeles Loneliness Scale (Version 3), Short Form 3-item (UCLA- LS3-SF3). The Impact of Event Scale-Revised (IES-R) assessed post-traumatic stress symptoms (PTSS) caused by the COVID-19 pandemic. The Patient Health Questionnaire-8 (PHQ-8) measured symptoms of depression. Resilience and concerns related to COVID-19 were also assessed. Descriptive statistics and linear regressions were conducted. Results The study population was n = 160 (SLE = 102, RA = 58), mean age 60.1 years (±13) and 21.9% (n=35) were men. Almost one third (28.1%) reported moderate to severe loneliness. (UCLA-LS3-SF3 score ≥6), with statistically significant difference between both disease groups (SLE = 36.3%; RA= 13.8%). Among participants with SLE, gender (men), psychological burden from the COVID-19 pandemic, and higher depressive symptoms were independently associated with greater loneliness, accounting for 38% of the variance (table 1). Among individuals living with RA, identifying as female and greater psychological burden from the COVID-19 pandemic were independently associated with greater loneliness, accounting for 55% of the variance. Discussion The results suggest that special attention to men with SLE and women with RA is needed when targeting loneliness in people with IRDs. More attention to strategies to decrease depressive symptoms and the psychological burden of the pandemic in patients living with IRDs are needed in future public health crises.

BackgroundThe role of type I and type III interferons (IFNs) in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) is still poorly understood. The objective of this study was to examine the hypothesis that IFN expression profiles in the peripheral blood differ between subsets of arthritic subjects. Multiple type I and type III IFNs were examined in patients with RA and JIA, as well as among subtypes of JIA.MethodsTreatment-naïve RA and JIA patients were enrolled. Droplet digital PCR was used to measure the expression of type I, II, and III interferons in blood and synovial fluid leukocytes. Dendritic cell subsets were isolated from synovial fluid to examine IFN expression in each subset. Additionally, synovial mononuclear cells and JIA-derived fibroblast-like synoviocytes were stimulated with TNF, IFNγ, and poly(I:C) to examine inducible IFN expression.ResultsThe predominant type I IFN gene expressed by blood leukocytes was IFNκ and was significantly lower in RA than JIA and controls. Oligoarticular and psoriatic JIA subgroups showed higher IFNκ expression compared to polyarticular JIA and RA. JIA synovial fluid leukocytes expressed abundant IFNγ and type III IFNs (IFNλ1, IFNλ3), with distinct dendritic cell subset contributions. JIA fibroblast-like synoviocytes produced IFNβ, IFNλ1, and IFNλ2 mRNA upon poly(I:C) stimulation.ConclusionThis study revealed differences in IFN expression patterns in RA and JIA, with notable differences between JIA subtypes. The expression levels of IFNκ, IFNγ, IFNλ1 and IFNλ3 in JIA suggest specific roles in disease pathology, influenced by disease subtype and joint microenvironment. This study contributes to understanding IFN-mediated mechanisms in arthritis, potentially guiding targeted therapeutic strategies.

Background Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort.Methods Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up.Results Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1).Conclusion Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis.

OBJECTIVE:To estimate direct and indirect costs associated with neuropsychiatric (NP) events in the Systemic Lupus International Collaborating Clinics inception cohort.METHODS:NP events were documented annually using American College of Rheumatology definitions for NP events and attributed to systemic lupus erythematosus (SLE) or non-SLE causes. Patients were stratified into 1 of 3 NP states (no, resolved, or new/ongoing NP event). Change in NP status was characterized by interstate transition rates using multistate modeling. Annual direct costs and indirect costs were based on health care use and impaired productivity over the preceding year. Annual costs associated with NP states and NP events were calculated by averaging all observations in each state and adjusted through random-effects regressions. Five- and 10-year costs for NP states were predicted by multiplying adjusted annual costs per state by expected state duration, forecasted using multistate modeling.RESULTS:A total of 1,697 patients (49% White race/ethnicity) were followed for a mean of 9.6 years. NP events (n = 1,971) occurred in 956 patients, 32% attributed to SLE. For SLE and non-SLE NP events, predicted annual, 5-, and 10-year direct costs and indirect costs were higher in new/ongoing versus no events. Direct costs were 1.5-fold higher and indirect costs 1.3-fold higher in new/ongoing versus no events. Indirect costs exceeded direct costs 3.0 to 5.2 fold. Among frequent SLE NP events, new/ongoing seizure disorder and cerebrovascular disease accounted for the largest increases in annual direct costs. For non-SLE NP events, new/ongoing polyneuropathy accounted for the largest increase in annual direct costs, and new/ongoing headache and mood disorder for the largest increases in indirect costs.CONCLUSION:Patients with new/ongoing SLE or non-SLE NP events incurred higher direct and indirect costs.

Objective The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow‐up. Methods The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models. Results Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244–566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80–6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05–3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43–20.39). Conclusion Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five‐year mortality. image