Findings from cross-sectional studies have revealed associations between DNA methylation and systemic lupus erythematosus (SLE) outcomes. This study was undertaken to investigate the dynamics of DNA methylation by examining participants from an SLE longitudinal cohort using samples collected at 2 time points.
Earlier age of SLE onset is associated with greater disease damage, even after taking into account the effects of current age and disease duration. We sought to determine if this association was consistent across racial and ethnic groups, given the differences in disease severity among these groups.
Methods
Data derive from the baseline visit of the California Lupus Epidemiology Study (CLUES), an ongoing cohort of patients in the San Francisco Bay Area with confirmed SLE diagnoses, drawn from a variety of clinical sources and prior SLE studies. Participants provided access to medical records and had a visit with a study physician in which clinical labs were drawn. Disease damage was measured using the SLICC/ACR Damage Index (SDI), calculated at the study visit. Age of diagnosis was ascertained by the study physician or from the medical records. Race/ethnicity (White, African American, Hispanic of any race, and Asian) and educational attainment (high school or less, some college, college graduate) were determined by patient report. Due to the small sample size, patients from other racial groups were excluded from this analysis (n=5). Using multiple linear regression, we estimated a model of SDI as a function of race/ethnicity and age of diagnosis, plus terms for interaction between the variables. The model controlled for sex, current age, and education.
Results
Among 323 participants, 89% were female, 39% Asian, 11% African American, 22% Hispanic of any race, and 29% White. Mean age was 45±14; mean age at diagnosis 29±12. Nearly half of respondents had a college degree. SDI at the baseline study visit ranged from 0 to 10 points, mean 1.8±2.0; 70% of the cohort had SDI>0. The regression model showed strong evidence (p=0.01) for interaction of age of diagnosis with race/ethnicity. As seen in the figure 1, SDI scores in racial/ethnic minorities were much higher among those diagnosed at younger ages; this relationship was not seen among whites.
Conclusions
In this multi-ethnic cohort of SLE patients, the association of diagnosis age and disease damage varied according to race/ethnicity, with whites diagnosed at younger ages accumulating less damage than those in other racial/ethnic groups diagnosed at comparable ages. Future research should examine if these differences are due to phenotypic differences among the groups, diagnostic delays, or other access to care issues.
Funding Source(s):
Centers for Disease Control and Prevention (U01 DP005120)
Frailty, a clinical syndrome of weight loss, weakness, slowness, exhaustion, and inactivity, has been examined primarily in geriatric populations, and is associated with poor health outcomes, including mortality. Components of the frailty syndrome are relevant to lupus, but frailty has not been examined in lupus.
Materials and methods
Subjects participated in a research visit in 2008–2009. Frailty was measured according to five components defined by Fried (2001): unintentional weight loss, slow gait (based on 4-metre walk using sex and height criteria), weakness (based on grip strength using gender and BMI criteria), exhaustion (2 specific questions), and inactivity (based on physical activity questionnaire). Accumulation of 3+ components classifies an individual as "frail," one or two components as "at risk," and none as "robust." Outcomes examined were physical function, cognitive function, and mortality. Physical function was measured with the SF-36 Physical Functioning subscale (scored 0–100) and the Valued Life Activities (VLA) disability scale (scored 0–3). Cognitive functioning was measured with a 12-test battery. Each test was classified as "impaired" if the score was below −1.0 SD of age-adjusted population norms. Subjects were classified as cognitively impaired if they were impaired on ≥one third of indices completed. Mortality was determined as of December 2015. Differences in function and two-year changes in function were examined using multiple regression analyses controlling for age, lupus duration, race/ethnicity, glucocorticoid use, obesity, self-reported disease activity and damage, and, for longitudinal analyses, baseline function. Mortality analyses controlled for age, lupus duration, and baseline disease damage scores. Analyses include women (n = 138).
Results
Mean age was 48 (± 12) years, mean lupus duration was 16 (± 9) years. 65% were white, non-Hispanic. 24% of the sample was classified as frail, and 48% as pre-frail. Frail women had significantly worse physical functioning than both robust and pre-frail women and were more likely to have cognitive impairment (Table 1). Frail women were also more likely to experience declines in functioning and onset of cognitive impairment. Ten women died during the follow-up period. Mortality rates were significantly higher in the frail group (frail 16.7%; pre-frail 4.1%; robust 2.3%). Odds (95% CI) of death for frail women were elevated, even after adjusting for age, lupus duration, and baseline disease damage (5.1 [0.5, 51.3]).
Conclusions
Prevalence of frailty in this sample of women with lupus was more than double that reported in older adults. Frailty was associated with poor physical and cognitive function, functional declines, and mortality.
Adults with ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis, are at a significantly increased risk of fracture relative to the general population. While some studies have evaluated the risk of fracture in AS, we do not have European or U.S. population-level studies assessing different fracture types performed within the last three decades.
Objectives
We evaluated the incidence rate and factors associated with fractures among those with AS using linked data from the national U.S. Rheumatology Informatics System for Effectiveness (RISE) registry and Medicare claims.
Methods
Data were derived from RISE, a large, national electronic health record-based registry, which was linked to Medicare claims from 2016-2018. Patients were required to have at least two visits for AS with a rheumatology provider, ≥ 30 days apart, prior to the baseline period of the study and at least one Medicare claim. One year of baseline characteristics was collected from both RISE and Medicare claims. Subjects were considered to have a historical fracture (vs. an incident fracture) if a fracture occurred prior to the index date. Patients were followed over time for incident fractures after the index date. Fractures were defined by ICD codes. We examined all fractures, including those of the vertebrae, sternum/ribs, shoulder/clavicle/upper arm/elbow, distal forearm/wrist/hand, pelvis/hip/femur, knee/lower leg, and ankle/foot. First, we calculated the combined incidence of fracture and incidence by fracture type. Second, logistic regression models were constructed to identify factors associated with fracture, including age, sex, race or ethnic group, national area deprivation index, dual-eligibility for Medicare (healthcare for adults aged 65+ and some people with certain conditions/disabilities) and Medicaid (healthcare for those with limited income and resources), Charlson comorbidity index, body mass index, smoking status, osteoporosis diagnosis, historical fracture (fracture prior to index date), and use of glucocorticoids and opioids.
Results
We identified 1,426 adults with AS in RISE who were also observable in Medicare. The mean (SD) age was 69.4 years (9.8), 44.3% were female, and 77.3% were non-Hispanic White. Fractures occurred in 197 AS adults (Table 1). The overall incidence rate of fractures among adults with AS was 76.7 (95% CI 66.4-88.6) per 1,000 person-years. The most common fracture was vertebral with an incidence rate of 23.9 per 1,000 person-years (95% CI 18.6-30.7), followed by distal forearm/wrist/hand with an incidence rate of 17.4 per 1,000 person-years (95% CI 13.0-23.4). Age 85+ (OR 3.64, 95% CI 1.79-7.40), historical fracture (OR 5.18, 95% CI 3.40-7.89), and use of opioid drugs (OR 2.20, 95% CI 1.52-3.19) conferred increased odds of fracture; sex did not (Figure 1).
Conclusion
In this large U.S. sample of older adults with AS, vertebral fractures were the most common followed by distal forearm/wrist/hand fractures. Those who were older, had a historical fracture and used opioids had higher odds of fracture. Men and women were equally likely to have a fracture. Since chronic opioid use was associated with fracture in AS, this high-risk population should be considered for interventions to mitigate risk. Model adjusted for all variables shown in the Figure 1.
REFERENCES:
NIL.
Acknowledgements:
NIL.
Disclosure of Interests
Rachael Stovall: None declared, Emma Kersey: None declared, Jing Li: None declared, Rahaf Baker: None declared, Christine Anastasiou: None declared, Andriko Palmowski: None declared, Gabriela Schmajuk: None declared, Lianne S. Gensler Consultant of: AbbVie, Acelyrin, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Novartis and UCB Pharma, Jinoos Yazdany Consultant of: Astra Zeneca, Pfizer, Aurinia, Grant/research support from: Astra Zeneca, BMS Foundation, Gilead and Aurinia.
Osteoporosis and fragility fractures are associated with significant morbidity for patients with systemic lupus erythematosus (SLE). New quality indicators (QIs) for SLE advise bone mineral density testing, calcium and vitamin D use, and antiresorptive or anabolic treatment for specific subgroups of patients receiving high-dose steroids.Subjects were participants in the University of California, San Francisco Lupus Outcomes Study, an ongoing longitudinal study of patients with physician-confirmed SLE, in 2007-2008. Patients responded to an annual telephone survey and were queried regarding demographic, clinical, and other health care-related variables. Multiple logistic regression was used to predict receipt of care per the QIs described above.One hundred twenty-seven patients met the criteria for the formal definitions of the denominators for QI I (screening) and QI II (calcium and vitamin D); 91 met the formal criteria for QI III (treatment). The proportions of patients receiving care consistent with the QIs were 74%, 58%, and 56% for QIs I, II, and III, respectively. In a sensitivity analysis of all steroid users (n = 427 for QI I and II and n = 224 for QI III), rates were slightly lower. Predictors of receiving care varied by QI and by denominator; however, female sex, older age, white race, and longer disease duration were associated with higher-quality care.Bone health-related care in this community-based cohort of SLE patients is suboptimal. Quality improvement efforts should address osteoporosis prevention and care among all SLE patients, especially those receiving high-dose, prolonged steroids.
Depression and cardiovascular disease are common and debilitating comorbidities associated with systemic lupus erythematosus (SLE). In this study, history of cardiovascular events, cardiovascular risk factors, and SLE disease-related factors were evaluated as longitudinal predictors of depression in a large cohort of patients with SLE.Data were derived from 663 adult participants in the 2004-2008 Lupus Outcomes Study, who were followed for up to 5 annual interviews. Multivariate logistic regression analyses using generalized estimating equations were used to determine predictors of the development of increased depressive symptom severity over a 12-month period (Center for Epidemiologic Studies Depression Scale [CES-D] score of 23 or greater), yielding 2,224 paired observations. Predictors included sociodemographics, traditional cardiovascular risk factors (reported presence of heart disease, history of stroke or myocardial infarction, hypertension, hypercholesterolemia, diabetes mellitus, obesity, smoking status, and family history), and SLE-specific risk factors (glucocorticoid use, renal involvement, disease duration, and disease activity).The annual incidence of depression was 12% in this cohort. Multivariate predictors of new-onset depression included younger age (ages 20-39 years: odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.3-3.9; ages 40-59 years: OR 1.8, 95% CI 1.1-2.7), Hispanic/Latino ethnicity (OR 1.8, 95% CI 1.2-2.8), having some college education (OR 1.8, 95% CI 1.1-3.0), baseline CES-D score (OR per point 1.1, 95% CI 1.1-1.2), presence of diabetes mellitus (OR 1.8, 95% CI 1.1-2.8), and baseline SLE disease activity (OR 1.2, 95% CI 1.1-1.4).These results suggest that, in addition to known sociodemographic factors, the presence of diabetes mellitus and SLE disease activity may play a role in the development of depression in SLE.
Introduction In recent years, the American College of Rheumatology (ACR) has focused increasingly on the development, review, dissemination, and implementation of quality measures. To help position rheumatology providers as the leading force in defining the quality of rheumatology care, the ACR convened a Quality Measures White Paper Development Workgroup. This diverse workgroup’s charge included synthesizing the information most relevant to the ACR membership regarding quality measurement. As described in this manuscript, the workgroup ultimately participated in a consensus development initiative to craft a set of criteria for quality measures submitted to the ACR for approval. The criteria are intended to guide measure developers and discourage adoption of subpar measures. This White Paper is written for rheumatologists interested in quality measurement, groups undertaking quality measure development, and policy makers. It is organized into the following main sections: a brief introduction provides context and describes the ACR’s national role and positions; section 1 outlines quality measure domains and reviews measure attributes; and section 2 describes and reports results of an ACR workgroup–led process to develop specific criteria for ACR approval of quality measures.
Abstract Objective In recent years hydroxychloroquine (HCQ) has emerged as a key therapy in systemic lupus erythematosus (SLE). We determined the rates of HCQ use in a diverse, community‐based cohort of patients with SLE and identified predictors of current HCQ use. Methods Patients were participants in the University of California San Francisco Lupus Outcomes Study, an ongoing longitudinal study of patients with confirmed SLE. We examined the prevalence of HCQ use per person‐year and compared baseline characteristics of users and nonusers, including demographic, socioeconomic, clinical, and health system use variables. Multiple logistic regression with generalized estimating equations was used to evaluate predictors of HCQ use. Results A total of 881 patients contributed 3,095 person‐years of data over 4 interview cycles. The prevalence of HCQ use was 55 per 100 person‐years and was constant throughout the observation period. In multivariate models, the odds of HCQ use were nearly doubled among patients receiving their SLE care from a rheumatologist compared with those identifying generalists or nephrologists as their primary sources of SLE care. In addition, patients with shorter disease duration were more likely to use HCQ, even after adjusting for age and other covariates. Conclusion In this community‐based cohort of patients, HCQ use was suboptimal. Physician specialty and disease duration were the strongest predictors of HCQ use. Patients who are not using HCQ, those with longer disease duration, and those who see nonrheumatologists for their SLE care should be targeted for quality improvement.
Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease in which outcomes vary among different racial groups. We leverage cell-sorted RNA-seq data (CD14+ monocytes, B cells, CD4+ T cells, and NK cells) from 120 SLE patients (63 Asian and 57 White individuals) and apply a four-tier approach including unsupervised clustering, differential expression analyses, gene co-expression analyses, and machine learning to identify SLE subgroups within this multiethnic cohort. K-means clustering on each cell-type resulted in three clusters for CD4 and CD14, and two for B and NK cells. To understand the identified clusters, correlation analysis revealed significant positive associations between the clusters and clinical parameters including disease activity as well as ethnicity. We then explored differentially expressed genes between Asian and White groups for each cell-type. The shared differentially expressed genes across cells were involved in SLE or other autoimmune-related pathways. Co-expression analysis identified similarly regulated genes across samples and grouped these genes into modules. Finally, random forest classification of disease activity in the White and Asian cohorts showed the best classification in CD4+ T cells in White individuals. The results from these analyses will help stratify patients based on their gene expression signatures to enable SLE precision medicine.
Abstract Objective To determine the validity of standardized screening assessments of cognitive functioning to detect neuropsychological impairment evaluated using a comprehensive battery in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods This is a cross‐sectional study using a combined cohort of 139 persons with SLE and 82 persons with RA. Screening cut points were empirically derived using receiver operating characteristic curves and threshold selection methods. Screening measures included the Hopkins Verbal Learning Test‐Revised (HVLT‐R) learning and delayed recall indices and phonemic fluency, a composite measure of the 3 cognitive screening tests, and the Perceived Deficits Questionnaire‐Short Form (PDQ‐SF), a self‐report measure of cognitive symptoms. A comprehensive neuropsychological battery was administered as the “gold standard” index of neuropsychological impairment. Results Rates of neuropsychological impairment were 27% and 15% for the SLE and RA cohorts, respectively. Optimal threshold estimations were derived for 5 screening techniques. The HVLT‐R learning and phonemic fluency indices yielded the greatest sensitivity at 81%. The PDQ‐SF yielded the lowest sensitivity at 52%. All measures were significantly associated with neuropsychological impairment after controlling for relevant sociodemographic covariates and depression. Conclusion These results suggest that telephone‐administered screening techniques may be useful measures to identify persons with neuropsychological impairment. Specifically, measures of phonemic fluency and verbal learning appeared to be most sensitive and least likely to misclassify impaired individuals as cognitively intact. Self‐reported questionnaires may have relatively decreased sensitivity compared to standardized interviewer‐administered cognitive measures.
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