OBJECTIVE:Using a hydroxychloroquine (HCQ) dose of 5 mg/kg/day in systemic lupus erythematosus (SLE) is associated with a higher risk of flares; HCQ blood level monitoring could be a better way to adjust the HCQ dose. We studied the upper threshold for a reference range of HCQ levels to inform routine monitoring. METHODS:This observational study included patients (N = 2,010) across the Systemic Lupus International Collaborating Clinics, Wisconsin, international, and French studies who underwent HCQ blood level measurements. Using adjusted spline and logistic regression analyses on the cross-sectional data, we first identified an HCQ blood level associated with higher HCQ toxicity. Next, we tested if this upper threshold level was supratherapeutic (no further risk reduction for the Systemic Lupus Erythematosus Disease Activity Index 2000 [score ≥6]). Finally, we examined associations between chronic kidney disease (CKD) stage and supratherapeutic (toxic) HCQ blood levels. RESULTS:Among 1,842 patients (excluding 168 patients with very low HCQ blood levels), 4.9% had HCQ-related toxicity. Odds of toxicity were 2.1-fold higher with blood levels ≥1,150 ng/mL and 1.7-fold higher with the cumulative HCQ dose per 1,000-g increase. Blood levels ≥1,150 ng/mL were associated with a saturation in therapeutic effect, indicating supratherapeutic levels. Patients with CKD stage ≥3 had 2.3-fold higher odds of having supratherapeutic levels (≥1,150 ng/mL). CONCLUSION:The therapeutic reference range for HCQ blood level monitoring is 750 to <1,150 ng/mL. HCQ level monitoring could optimize HCQ use, particularly in patients with CKD stage ≥3. Future longitudinal studies are needed to validate the use of HCQ blood level monitoring in optimizing dosing.

Objective Epidemiologic data on falls in the population with systemic lupus erythematosus (SLE) remain sparse. We estimated the prevalence and correlates of falls among adults with SLE and compared SLE prevalence estimates with those in the general US population. Methods We assessed falls in a nested cross-sectional study within two pooled population-based SLE cohorts in California (3/2025–2/2026) and Georgia (10/2019–5/2022). Stratified prevalence was assessed with marginal estimates from logistic regression models with falls as the outcome. Age-standardised and sex-standardised estimates in SLE were compared with 2023 US population estimates (ages ≥45 only). Results In this pooled SLE cohort (N=780; mean age, 47.9; 91.9% women; 14.5% Asian, 51.7% black, 13.2% Hispanic), 26.0% reported any fall in the prior year; among these, 59.1% reported falling two times or more and 31.0% reported associated injuries. General factors (oldest vs youngest age (37.4% vs 20.7% for ≥65 vs 20–44)) and SLE-related factors (higher SLE activity (38.5% vs 13.5%), moderate-to-severe depressive symptoms (40.0% vs 23.7%), greater pain interference (43.8% vs 16.5%), greater fatigue (39.2% vs 18.8%) and lower cognitive function (39.7% vs 18.9%)) were statistically significantly associated with higher fall prevalence in the SLE cohort. Among those aged ≥45, the age-standardised and sex-standardised prevalence estimate in the SLE population (22.9%) was similar to the US population estimate (19.5%). Conclusion The prevalence of falls in SLE is high and recurrence is common, suggesting clinical assessment of falls—especially in those with high disease activity and symptoms—is important in SLE.

Objective The value of comprehensive geriatric assessment (CGA) in the setting of chronic disease, regardless of age, has been increasingly recognised. We examined whether geriatric conditions identified by measures commonly used in CGA were associated with subsequent acute care utilisation among individuals with SLE.Methods In this longitudinal cohort study, data from participants from a population-based cohort of adults (≥18 years) with validated SLE were included if they completed a study visit during which data on CGA measures were collected and a subsequent (12–24 months later) questionnaire that included items on emergency department (ED) visit and hospital admissions. Associations (incidence rate ratios (IRRs)) of CGA-identified conditions (impairments in physical or cognitive performance; limitations in self-reported physical function or instrumental or basic activities of daily living (ADLs); restrictions in community mobility; polypharmacy; urinary incontinence) with ED visits and hospital admissions were assessed with multivariable negative binomial models, adjusting for demographic and clinical characteristics.Results Nearly all (97.1%) participants (n=241; mean age, 45.9; 93.0% female; 83.8% black) had at least one CGA-identified condition. Those with CGA-identified conditions with physical performance (IRR=1.69, 95% CI 1.17 to 2.43), cognitive performance (IRR=2.24; 95% CI 1.32 to 3.79), self-reported physical function (IRR=1.77; 95% CI 1.10 to 2.85), basic ADLs (IRR=1.55, 95% CI 1.09 to 2.20) and falls (IRR=1.57; 95% CI 1.08 to 2.27) had higher rates of ED visits. However, after full adjustment, only cognitive impairment was statistically significantly associated with ED visits (IRR=1.79; 95% CI 1.05 to 3.03) and hospital admissions (IRR=2.44; 95% CI 1.20 to 4.96).Conclusions Identification of CGA-identified conditions, particularly cognitive impairment, may be useful for mitigating the risk of subsequent acute care utilisation among patients with SLE. Future studies should examine the effectiveness of CGA measures in improving other important outcomes, such as patient quality of life and satisfaction.

OBJECTIVE:This study attempted to quantify the bias expected due to partly interval-censored (IC) outcomes in the estimated association between hydroxychloroquine (HCQ) taper/cessation and time to disease flare among individuals with systemic lupus erythematosus (SLE). METHODS:Using data-driven simulations, we estimated bias expected due to IC using real-world data from the Systemic Lupus International Collaborating Clinics inception cohort. The time-varying exposure of interest was a binary indicator of HCQ tapering/cessation. The composite outcome was lupus flare, defined as lupus hospitalizations or increases in disease activity or medication dose. The two latter components were IC, as they were recorded only at annual assessment, without a precise date. For the unknown IC event times, a "true" event time was randomly generated from a uniform distribution of the time between two assessments. Each simulated sample was analyzed separately imputing unknown event times (for IC outcomes) either at the midpoint or endpoint of the interval between the two adjacent yearly assessments. Results of multivariable Cox proportional hazards models, adjusted for demographics, drugs, and clinical variables, using either "true" or imputed IC event times were compared. RESULTS:The 1543 SLE patients were followed for a median of 42.2 months. During follow-up, 396 participants tapered/stopped HCQ and 1187 experienced a flare. The adjusted uncorrected hazard ratio was 1.51 (95% confidence interval: 1.30, 1.75) and 1.40 (95% confidence interval: 1.21, 1.62) for midpoint and endpoint imputations, respectively. Data-driven simulations showed that imputation of IC event times resulted in a small but systematic bias toward the null that was consistently larger for endpoint than for midpoint imputation. CONCLUSIONS:IC events induced bias toward the null in the estimated association between HCQ taper/cessation and lupus flares. Data-driven simulations are useful for quantitative bias analyses in complex situations, as they allow accounting for relevant characteristics of a particular real-world dataset.

Introduction SLE remains a disease of high unmet medical need. Protean manifestations and the lack of clear understanding of aetiology, pathogenesis and disease subgroups make it difficult to develop and employ targeted therapeutic approaches. Community-wide access to a longitudinal, highly curated patient dataset with linked biospecimens and cellular/molecular data is critical to enable advances and is now provided by Lupus Nexus (LNx). In this study, we describe the development of this unique resource with exemplary patient engagement. Methods and analysis LNx, developed with guidance from over 100 partners, includes a prospective, longitudinal observational study, the Lupus Landmark Study (LLS), that will enrol up to 3500 adults living with lupus into four cohorts and will follow them over 5 years. The registry data comprises medical information, clinician-reported and patient-reported outcomes while the biorepository includes whole blood, urine, saliva, stool and tissue which are available to the research community for a broad range of analyses. Importantly, since all raw data from the biospecimen analyses will be deposited in LNx, it will amass a deep and comprehensive dataset over time. As of 25 March 2026, there are 705 enrolled participants (13.3% new onset, 27.4% extrarenal flare, 23.3% active lupus nephritis and 35% prevalent cases, with 37.6% black, 38% white and 12.6% Asian/Pacific Islander patients). Over 15 400 unique samples have been collected and specific analyses are underway. All data and samples from LNx are available via its Data Repository Exchange and Analytics platforM ( DREAM ). Importantly, a dedicated patient portal within DREAM enables participants to view their study data, connect with others and learn about the research emerging from projects using LNx. Trial registration number NCT05934149 .

Gendered racism, rooted in the interlocking injustices of racism and sexism, is a contributor to poor mental health; its association with physical health outcomes, however, is not well understood. This study investigates whether gendered racism is associated with disease activity among Black women living with systemic lupus erythematosus (SLE). Data are from the Vascular Aging, Inflammation, and Stress in African American Women's Health Research Study (VISTA; 2017-2023). Analyses were restricted to Black women with SLE (N = 201). Results revealed more frequent gendered racism experiences were associated with greater disease activity; this association was attenuated yet remained significant after adjustment for depressive symptoms. Gendered racism experiences linked to Assumptions of Beauty and Sexual Objectification were most consistently associated with disease activity. Study results underscore the importance of examining intersectional injustice (e.g., gendered racism) as a social determinant of health.

OBJECTIVE:Estimates of polypharmacy among US adults with systemic lupus erythematosus (SLE)-a relatively young and disproportionately minoritized population-remain sparse. We sought to estimate the prevalence of polypharmacy in SLE and identify the most common medications used. METHODS:For this cross-sectional study, participants were recruited from a population-based cohort of adults with validated SLE in Atlanta, Georgia. Prescription and over-the-counter (OTC) medications were self-reported at the study visit. Polypharmacy was defined as five or more prescription or OTC medications. Estimates of polypharmacy prevalence by key sociodemographic and SLE-related participant characteristics were obtained using crude logistic regression and postestimation marginals. RESULTS:More than half (56.3%) of participants (n = 451; 15.3% ≥60 years old, 91.8% women, and 81.8% Black) reported polypharmacy. Older age (68.1%, 59.8%, and 43.0% for ages ≥60 years, 40-59 years, and 18-39 years), higher vs lower disease activity (65.8% vs 46.2%) and cumulative SLE-related damage (68.5% vs 42.4%), longer disease duration (62.4% vs 50.0%), and taking three to five vs zero to one immunomodulating medications (79.6% vs 38.0%) were associated with higher age-adjusted prevalence of polypharmacy; prevalence was not statistically significantly different by sex, race, or education. Although hydroxychloroquine (71.4%), glucocorticoids (44.3%), and other immunomodulating drugs (50.3%) were common, polypharmacy was most often driven by other medications, such as antihypertensives (61.9%), nonopioid pain relievers (51.7%), allergy treatments (22.4%), antidepressants (22.2%), and gastric reflux medications (21.7%). CONCLUSION:Our results underscore the need to address the burden of medication regimens in this population through individualized medication optimization strategies that account for prescription and OTC medications used by those with SLE.

OBJECTIVE:We leveraged data from 2 population-based systemic lupus erythematosus (SLE) cohorts (Approaches to Positive, Patient-Centered Experiences of Aging With Lupus [APPEAL] and the California Lupus Epidemiology Study [CLUES]) to provide estimates of, and identify factors associated with, perceived and objective physical function (PF) and their discordance. METHODS:Perceived PF (Patient-Reported Outcomes Measurement Information System [PROMIS] 12a/10a [APPEAL/CLUES]; t-scores [mean 50, SD 10]) and objective PF (Short Physical Performance Battery [SPPB]; score range 0-12) were examined by cohort and participant characteristics (higher scores indicated better function). We assessed factors associated with discordance between scores (≥ 2 quartile difference) using multinomial logistic regression. RESULTS:APPEAL (N = 446; 81.4% Black) vs CLUES (N = 173; 41% Asian, 27.7% White, 23.1% Hispanic) participants had lower perceived PF (PROMIS t-scores, 41.5 vs 47.9) and objective PF (SPPB scores, 9.0 vs 9.4). There was no difference after adjustment for disease activity and cumulative disease damage. Factors associated with lower perceived PF and objective PF across cohorts included oldest vs youngest age (t-scores, 40.8 vs 47.4; SPPB scores, 8.9 vs 9.6), Black vs White race (t-scores, 40.8 vs 45.6; SPPB scores, 8.9 vs 9.7), and higher vs lower disease activity (t-scores, 38.1 vs 48.4; SPPB scores, 8.7 vs 9.6). Overall, 22.4% of participants had discordant scores; older age and higher disease activity were independently associated with lower risk of overestimating PF (objective score < perceived score). CONCLUSION:Our findings show that perceived and objective PF can vary considerably across SLE populations and patient characteristics. Perceived PF may not always reflect objective PF in SLE populations.

OBJECTIVE:Epidemiologic estimates for age of systemic lupus erythematosus (SLE) diagnosis are limited, particularly for men and racial and ethnic subpopulations in the United States. Leveraging the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population-based SLE registries, meta-analyses were performed estimating age-specific incidence of SLE by sex, race, and ethnicity. METHODS:The CDC network of SLE registries includes five state-based registries, plus a sixth Indian Health Service registry. Incidence periods spanned calendar years 2002-2018. Registries provided age-specific incidence of SLE, fulfilling the American College of Rheumatology (ACR) SLE classification criteria, per 100,000 person-years, stratified by sex, race, and ethnicity for the meta-analyses. RESULTS:Incidence rates among women were highest for those aged 30-39 (12.7, 95%CI: 9.5-16.8), while rates among men were highest for those aged 60-69 (2.1, 95%CI: 1.3-3.4). Black women aged 20-39 had the highest SLE incidence rates (23.6, 95%CI: 20.7-26.8). Among women diagnosed with SLE before age 20, incidence was highest among Asian (6.5, 95%CI: 2.8-15.2) individuals. Among women diagnosed with SLE after age 60, incidence was highest among American Indian/Alaska Native (9.4, 95%CI: 3.4-15.4) individuals. Weighted percentages show 10.0% of those with SLE were diagnosed before age 20, while 15.1% were diagnosed after age 60. The largest proportion of individuals with SLE, 22.1%, were diagnosed between 30-39 years. CONCLUSIONS:This study provides comprehensive sex- and race-specific estimates of age at SLE diagnosis. The substantial later in life SLE incidence among men and disease burden in pediatric and older populations should raise awareness in considering SLE in the differential diagnosis in previously underrecognized groups.

OBJECTIVE:Strategies to Embrace Living with Lupus Fearlessly (SELF) is an online self-management education programme for people with SLE. This mixed-methods study examines SELF's impact on patient-reported outcomes while assessing implementation outcomes informing feasibility and dissemination. METHODS:A convergent mixed-methods design was used, merging qualitative and quantitative data to enhance interpretation. The Reach, Effectiveness, Adoption, Implementation and Maintenance evaluation framework was used to evaluate programme feasibility and sustainment potential. Participants were recruited from the Georgians Organized Against Lupus (GOAL) cohort (Georgia). RESULTS:221 adults with SLE from the GOAL cohort enrolled in SELF, completing patient-reported assessments at baseline and 90-day follow-up. 12 participants also completed in-depth interviews exploring the impact of the programme. Certain subgroups including black participants (n=193; 95% CI=-1.59 to -0.04), those with high fatigue levels (n=164; 95% CI=-1.85 to -0.11) and participants living below 100% of the federal poverty level (n=74; 95% CI=-3.44 to -0.18) reported significantly lower disease activity at 90-day follow-up after engaging with SELF. High-fatigue participants improved on multiple measures while the low-fatigue group showed unexpected declines that may reflect baseline confounding. Qualitative findings generally supported quantitative results. One exception was self-efficacy in managing medications, which showed a small but significant decrease (mean reduction=-1.38, 95% CI=-2.50 to -0.26, Cohen's d=-0.14). However, qualitative data suggested participants became more aware of skill gaps rather than less capable. CONCLUSIONS:SELF showed promising results for reducing disease activity, pain and fatigue among specific subgroups of participants with SLE. Further research should broaden the evaluation of SELF to new geographical settings, broader populations (such as people living with lupus in rural healthcare settings) and further testing for cultural relevance across diverse racial and ethnic groups.

Superwoman Schema is a multidimensional framework that describes how Black women manage interpersonal and societal roles. This cross-sectional study examined how patterns of Superwoman Schema subscales (obligations to manifest strength, suppress emotions, resist vulnerability, and help others, and intense motivation to succeed) and socioeconomic status (SES; perceived financial strain, income-to-poverty ratio, and education) related to self-reported disease activity among 437 Black women in metropolitan Atlanta, Georgia with systemic lupus erythematosus (SLE). Latent profile analysis identified three typologies: Strained Superwomen (high on Superwoman dimensions with low SES), Low Superwomen (low on Superwoman dimensions with average SES), and Resourced, Striving Superwoman (above average obligation to manifest strength and intense motivation to succeed with high SES). After accounting for covariates, Strained Superwomen had the highest self-reported disease activity. These results suggest that endorsement of Superwoman Schema is common among Black women with SLE and is related to more disease activity in low-resourced contexts.

OBJECTIVE:To evaluate how modifiable psychosocial factors and fatigue relate to physical functioning in patients with systemic lupus erythematosus (SLE). METHODS:In this cross-sectional study of two demographically distinct cohorts (Approaches to Positive, Patient-Centered Experiences of Aging with Lupus [APPEAL] and California Lupus Epidemiology Study [CLUES]), perceived physical function was assessed using Patient-Reported Outcomes Measurement Information System Physical Function Short Forms 12a (APPEAL) and 10a (CLUES). Fatigue, depression, and stress; coping efficacy and learned helplessness (APPEAL); and resilience and self-efficacy (CLUES) were all assessed with validated questionnaires. We used multivariable linear regression analyses to assess associations between perceived physical function and outcomes, adjusting for age, sex, and race, then further for disease damage and activity. RESULTS:APPEAL participants (N = 451) were primarily Black (82.5%); CLUES participants (N = 580) were predominantly Asian (29.3%), Hispanic (22.9%), and White (27.4%). Mean physical function T scores were lower in APPEAL (43.6) versus CLUES (47.2; P < 0.05). In both cohorts, higher fatigue, depression, and perceived stress were strongly associated with poorer physical function. Greater resilience (per +1 SD: β = 2.04, 95% confidence interval [CI] 0.57-3.50) and self-efficacy (high vs low: β = 13.53, 95% CI 8.69-18.37) (both in CLUES) and better coping (per +1 SD: β = 3.15, 95% CI 2.39-3.91; in APPEAL) were associated with better physical function. In APPEAL, greater learned helplessness was associated with worse physical function (per +1SD: β = -3.88, 95% CI -4.62 to -3.14). Although adjusting further for disease damage and activity attenuated these associations, they remained statistically significant. CONCLUSION:Our results demonstrate associations of fatigue and psychosocial factors with physical functioning, reinforcing their relationship with overall health in SLE.

OBJECTIVES:There is increasing recognition of the need for patient-centred lupus self-management (SM) programmes to improve outcomes. The purpose of this manuscript is to describe the underlying methodology and initial pilot results of Strategies to Embrace Living with Lupus Fearlessly (SELF): an evidence-based digital SM intervention designed for individuals with lupus based on the Transtheoretical Model of Behaviour Change. METHODS:We describe pilot testing and initial feasibility and acceptability results of SELF among individuals with lupus. Participants for the 90-day pilot test were recruited through three Centers for Disease Control & Prevention-funded lupus registry sites across the USA and the Lupus Foundation of America's constituency, including a diverse sociodemographic lupus population, using varied sources. Feasibility, acceptability and preliminary impact were assessed using data on enrolment, retention, ease of utilisation and satisfaction with SELF's features, changes in readiness for SM behaviours, impact on patient-reported outcomes (eg, fatigue interference) and user feedback. RESULTS:Nearly 80% of participants had moderate or high skill gaps at programme intake (ie, were in an early stage of change for a key SM skill), underscoring the importance of digital SM programmes like SELF. Among those who completed the programme, almost 60% of participants closed a skill gap by mastering one or more SM skills. Significant effects on patient-provider interactions and fatigue interference were also noted, highlighting a need for future investigation. Qualitative data were mostly positive in terms of feasibility and acceptability, with specific recommendations for future improvement. CONCLUSIONS:SELF utilisation and pilot data indicate that SELF is generally feasible and acceptable, particularly among those needing to build lupus SM skills. Future work will explore ways to improve the digital SM intervention and reduce barriers to initial and ongoing engagement.

OBJECTIVE:The objective of this study was to examine the clinical outcomes during the implementation of a self-administered patient decision-aid (PtDA) for lupus. METHODS:We provided an effective computerized lupus PtDA in 15 rheumatology outpatient clinics 2019-2024 (including the COVID pandemic). We undertook Organizational Readiness to Implement Change Surveys (ORICs) and Team Learning and Psychological Safety Surveys (TLPSSs) at baseline. The primary study outcome objective measure, percent penetration/reach, was defined as the number of patients who viewed the lupus PtDA at the end of the study, divided by the total number of eligible patients (times 100). We used validated clinical personnel surveys to examine the perceived lupus PtDA appropriateness, acceptability, feasibility, success, and permanence, at 4 months, 12 months and 24 months post-PtDA implementation. RESULTS:Among the sites, the clinical personnels' (n = 184) baseline ORIC commitment and efficacy scores (a 0-5 scale, higher = better) ranged from 3.5 to 4.2, and 3.4 to 4.4, respectively; the TLPSS scores (a 0-7 scale, higher = better) were 3.9-5.5 for internal learning, 3.7-5.6 for external learning, and 4.3-5.5 for psychological safety. The penetration (primary outcome) among 15 geographically diverse US rheumatology clinics ranged from 3% to 44%. We found that the total number of providers in the clinic was positively associated with higher penetration. Clinical personnel-perceived lupus PtDA outcomes were optimal at 4 months (all scale scores ranged from 1 to 5, higher = better): (i) appropriateness, 3.43 (s.d. 0.86); (ii) acceptability, 3.53 (s.d. 0.83); (iii) feasibility, 3.44 (s.d. 0.71); (iv) success, 3.41 (s.d. 0.73); and (v) permanence, 3.22 (s.d. 0.74). CONCLUSION:We implemented a lupus PtDA with varied success rates during the COVID pandemic; more providers were associated with higher clinic penetration. Clinical personnel perceived high lupus PtDA appropriateness, acceptability, feasibility, success, and permanence that persisted up to 24 months. TRIAL REGISTRATION:ClinicalTrials.gov, http://clinicaltrials.gov, NCT03735238.

OBJECTIVE:Hydroxychloroquine (HCQ) protects kidney function in lupus nephritis (LN) by preventing flares, yet some cohort studies show no significant benefit in kidney function with HCQ. Clarifying these conflicting findings by showing early and long-term benefits of HCQ on kidney function preservation is critical. Therefore, we analyzed data from our retrospective longitudinal inception LN cohort to examine the time-varying effects of HCQ on kidney function decline in LN. METHODS:We analyzed retrospective data from an incident biopsy-proven LN cohort. Creatinine values at LN diagnosis through the last follow-up were abstracted to find the estimated glomerular filtration rate (eGFR). Using HCQ exposure as a time-dependent covariate, we examined associations between HCQ exposure and sustained eGFR decline ≥30% and ≥40%. We also calculated an annual eGFR slope decline by HCQ exposure using linear mixed-effects analysis. RESULTS:Among 209 patients, 33% and 23% experienced eGFR decline ≥30% and ≥40% over time. Time-varying HCQ exposure was associated with a 60% and 62% lower risk of eGFR decline of ≥30% or ≥40%, after adjusting for propensity scores. A 77% lower risk of eGFR decline was noted in patients with chronic kidney disease (CKD) stage ≥3 with HCQ. HCQ exposure reduced the annual eGFR slope decline by 5.12 and 3.17 mL/min/1.73 m2 within the first 5 and 10 years of diagnosis. CONCLUSION:HCQ use was associated with early and long-term benefits on kidney function in LN, including those with CKD stage ≥3. Universal HCQ use should be encouraged in LN patients.