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Objectives: Medication access and adherence play key roles in determining patient outcomes. We investigated whether cost-related non-adherence (CRNA) to prescription medications was associated with worse patient-reported outcomes in a population-based systemic lupus erythematosus (SLE) cohort. Methods: Sociodemographic and prescription data were collected by structured interviews in 2014–2015 from patients meeting SLE criteria in the established Michigan Lupus Epidemiology & Surveillance (MILES) Cohort. We examined the associations between CRNA and potential confounders such as sociodemographics and health insurance coverage, and outcome measures of SLE activity and damage using multivariable linear regression. Results: 462 SLE participants completed the study visit: 430 (93.1%) female, 208 (45%) Black, and mean age 53.3 years. 100 (21.6%) participants with SLE reported CRNA in the preceding 12 months. After adjusting for covariates, CRNA was associated with both higher levels of current SLE disease activity [SLAQ: β coeff 2.7 (95% CI 1.3, 4.1), p < 0.001] and damage [LDIQ β coeff 1.4 (95% CI 0.5, 2.4), p = 0.003]. Race, health insurance status, and fulfilling Fibromyalgia (FM) Survey Criteria were independently associated with both higher (worse) SLAQ and LDIQ scores; female sex was further associated with higher SLAQ scores. Conclusion: Patients with SLE who reported CRNA in the previous 12 months had significantly worse self-reported current disease activity and damage scores compared to those not reporting CRNA. Raising awareness and addressing barriers or concerns related to financial implications and accessibility issues in care plans may help to improve these outcomes. [ABSTRACT FROM AUTHOR]

Objective: Medication access and adherence are important determinants of health outcomes. We investigated factors associated with access and cost‐related nonadherence to prescriptions in a population‐based cohort of systemic lupus erythematosus (SLE) patients and controls. Methods: Detailed sociodemographic and prescription data were collected by structured interview in 2014–2015 from participants in the Michigan Lupus Epidemiology and Surveillance (MILES) cohort. We compared access between cases and frequency‐matched controls and examined associated factors in separate multivariable logistic regression models. Results: A total of 654 participants (462 SLE patients, 192 controls) completed the baseline visit; 584 (89%) were female, 285 (44%) were Black, and the mean age was 53 years. SLE patients and controls reported similar frequencies of being unable to access prescribed medications (12.1% versus 9.4%, respectively; P was not significant). SLE patients were twice as likely as controls to report cost‐related prescription nonadherence in the preceding 12 months to save money (21.7% versus 10.4%; P = 0.001) but were also more likely to ask their doctor for lower cost alternatives (23.8% versus 15.6%; P = 0.02). Disparities were found in association with income, race, and health insurance status, but the main findings persisted after adjusting for these and other variables in multivariable models. Conclusion: SLE patients were more likely than controls from the general population to report cost‐related prescription nonadherence, including skipping doses, taking less medicine, and delaying filling prescriptions; yet, <1 in 4 patients asked providers for lower cost medications. Consideration of medication costs in patient decision‐making could provide a meaningful avenue for improving access and adherence to medications. [ABSTRACT FROM AUTHOR]

Objective: Epidemiologic data on systemic lupus erythematosus (SLE) are limited, particularly for racial/ethnic subpopulations in the US. This meta‐analysis leveraged data from the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population‐based SLE registries to estimate the overall prevalence of SLE in the US. Methods: The CDC National Lupus Registry network includes 4 registries from unique states and a fifth registry from the Indian Health Service. All registries defined cases of SLE according to the American College of Rheumatology (ACR) 1997 revised classification criteria for SLE. Case findings spanned either 2002–2004 or 2007–2009. Given the heterogeneity across sites, a random‐effects model was used to calculate the pooled prevalence of SLE. An estimate of the number of SLE cases in the US was generated by applying sex/race‐stratified estimates to the 2018 US Census population. Results: In total, 5,417 cases were identified as fulfilling the ACR SLE classification criteria. The pooled prevalence of SLE from the 4 state‐specific registries was 72.8 per 100,000 person‐years (95% confidence interval [95% CI] 65.3–81.0). The prevalence estimate was 9 times higher among females than among males (128.7 versus 14.6 per 100,000), and highest among Black females (230.9 per 100,000), followed by Hispanic females (120.7 per 100,000), White females (84.7 per 100,000), and Asian/Pacific Islander females (84.4 per 100,000). Among males, the prevalence of SLE was highest in Black males (26.7 per 100,000), followed by Hispanic males (18.0 per 100,000), Asian/Pacific Islander males (11.2 per 100,000), and White males (8.9 per 100,000). The American Indian/Alaska Native population had the highest race‐specific SLE estimates, both among females (270.6 per 100,000) and among males (53.8 per 100,000). In 2018, an estimated 204,295 individuals (95% CI 160,902–261,725) in the US fulfilled the ACR classification criteria for SLE. Conclusion: A coordinated network of population‐based SLE registries provides more accurate estimates of the prevalence of SLE and the numbers of individuals affected with SLE in the US in 2018. [ABSTRACT FROM AUTHOR]

Environmental factors can influence epigenetic regulation, including DNA methylation, potentially contributing to systemic lupus erythematosus (SLE) development and progression. We compared methylation of the B cell costimulatory CD70 gene, in persons with lupus and controls, and characterized associations with age. In 297 adults with SLE and 92 controls from the Michigan Lupus Epidemiology and Surveillance (MILES) Cohort, average CD70 methylation of CD4+ T cell DNA across 10 CpG sites based on pyrosequencing of the promoter region was higher for persons with SLE compared to controls, accounting for covariates [β = 2.3, p = 0.011]. Using Infinium MethylationEPIC array data at 18 CD70- annoted loci (CD4+ and CD8+ T cell DNA), sites within the promoter region tended to be hypo methylated in SLE, while those within the gene region were hyper methylated. In SLE but not controls, age was significantly associated with pyrosequencing-based CD70 methylation: for every year increase in age, methylation increased by 0.14 percentage points in SLE, accounting for covariates. Also within SLE, CD70 methylation approached a significantly higher level in Black persons compared to White persons (β = 1.8, p = 0.051). We describe altered CD70 methylation patterns in T lymphocyte subsets in adults with SLE relative to controls, and report associations particular to SLE between methylation of this immune-relevant gene and both age and race, possibly a consequence of "weathering" or accelerated aging which may have implications for SLE pathogenesis and potential intervention strategies. • Epidemiologic studies can provide novel insights about autoimmune conditions. • Locus-specific methylation of T cell DNA differed in SLE cases compared to controls. • Methylation of the immune-relevant CD70 gene increased with age in SLE only. • Adjusted for age, methylation of this gene also differed by race in SLE. [ABSTRACT FROM AUTHOR]

Rheumatic diseases are a leading cause of chronic, noncancer pain. Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease characterized by periodic flares that can result in irreversible target organ damage, including end-stage renal disease. Both intermittent and chronic musculoskeletal pain, as well as fibromyalgia (considered a centralized pain disorder due to dysregulation of pain processing in the central nervous system), are common in SLE. Opioids are generally not indicated for long-term management of musculoskeletal pain or centralized pain (fibromyalgia) because of lack of efficacy, safety issues ranging from adverse medical effects to overdose, and risk for addiction (1,2). In this study of 462 patients with SLE from the population-based Michigan Lupus Epidemiology and Surveillance (MILES) Cohort and 192 frequency-matched persons without SLE, nearly one third (31%) of SLE patients were using prescription opioids during the study period (2014-2015), compared with 8% of persons without SLE (p<0.001). Among the SLE patients using opioids, 97 (68%) were using them for >1 year, and 31 (22%) were concomitantly on two or more opioid medications. Among SLE patients, those using the emergency department (ED) were approximately twice as likely to use prescription opioids (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3-3.6; p = 0.004). In SLE, the combined contributions of underlying disease and adverse effects of immunosuppressive and glucocorticoid therapies already put patients at higher risk for some known adverse effects attributed to long-term opioid use. Addressing the widespread and long-term use of opioid therapy in SLE will require strategies aimed at preventing opioid initiation, tapering and discontinuation of opioids among patients who are not achieving treatment goals of reduced pain and increased function, and consideration of nonopioid pain management strategies. [ABSTRACT FROM AUTHOR]

Objectives. We assessed the burden of systemic lupus erythematosus (SLE) among Arab and Chaldean Americans residing in southeast Michigan. Methods. For those meeting SLE criteria from the Michigan Lupus Epidemiology and Surveillance Registry, we determined Arab or Chaldean ethnicity by links with demographic data from birth certificates and with a database of Arab and Chaldean names. We compared prevalence and incidence of SLE for Arab and Chaldean Americans with estimates for non-Arab and non-Chaldean American Whites and Blacks. Results. We classified 54 individuals with SLE as Arab and Chaldean Americans. The age-adjusted incidence and prevalence estimates for Arab and Chaldean Americans were 7.6 and 62.6 per 100 000, respectively. Arab and Chaldean Americans had a 2.1-fold excess SLE incidence compared with non-Arab and non-Chaldean American Whites. Arab and Chaldean American women had both significantly higher incidence rates (5.0-fold increase) and prevalence estimates (7.4-fold increase) than did Arab and Chaldean American men. Conclusions. Recognizing that Arab and Chaldean Americans experience different disease burdens from Whites is a first step toward earlier diagnosis and designing targeted interventions. Better methods of assigning ethnicity would improve research in this population. (Am J Public Health. 2015;105:e74–e79. doi:10.2105/AJPH. 2014.302423) [ABSTRACT FROM AUTHOR]

Objective To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in a sociodemographically diverse southeastern Michigan source population of 2.4 million people. Methods SLE cases fulfilling the American College of Rheumatology classification criteria (primary case definition) or meeting rheumatologist-judged SLE criteria (secondary definition) and residing in Wayne or Washtenaw Counties during 2002-2004 were included. Case finding was performed from 6 source types, including hospitals and private specialists. Age-standardized rates were computed, and capture-recapture was performed to estimate underascertainment of cases. Results The overall age-adjusted incidence and prevalence (ACR definition) per 100,000 persons were 5.5 (95% confidence interval [95% CI] 5.0-6.1) and 72.8 (95% CI 70.8-74.8). Among females, the incidence was 9.3 per 100,000 persons and the prevalence was 128.7 per 100,000 persons. Only 7 cases were estimated to have been missed by capture-recapture, adjustment for which did not materially affect the rates. SLE prevalence was 2.3-fold higher in black persons than in white persons, and 10-fold higher in females than in males. Among incident cases, the mean ± SD age at diagnosis was 39.3 ± 16.6 years. Black SLE patients had a higher proportion of renal disease and end-stage renal disease (ESRD) (40.5% and 15.3%, respectively) as compared to white SLE patients (18.8% and 4.5%, respectively). Black patients with renal disease were diagnosed as having SLE at younger age than white patients with renal disease (mean ± SD 34.4 ± 14.9 years versus 41.9 ± 21.3 years; P = 0.05). Conclusion SLE prevalence was higher than has been described in most other population-based studies and reached 1 in 537 among black female persons. There were substantial racial disparities in the burden of SLE, with black patients experiencing earlier age at diagnosis, >2-fold increases in SLE incidence and prevalence, and increased proportions of renal disease and progression to ESRD as compared to white patients. [ABSTRACT FROM AUTHOR]

Objective To determine the value of cell-bound complement activation products in combination with antinuclear antibody (ANA), anti-double-stranded DNA antibody (anti-dsDNA), and anti-mutated citrullinated vimentin antibody (anti-MCV) for the diagnosis of systemic lupus erythematosus (SLE). Methods This was a multicenter cross-sectional study in which 593 subjects were enrolled (210 SLE patients, 178 patients with other rheumatic diseases, and 205 healthy subjects). Complement receptor 1 levels on erythrocytes (ECR1) together with complement C4d levels on erythrocytes (EC4d), platelets (PC4d), and B cells (BC4d) were determined using fluorescence-activated cell sorting. Serologic markers were measured by enzyme-linked immunosorbent assay. Statistical analyses were performed using area under the curve (AUC), logistic regression, and calculations of diagnostic sensitivity and specificity. Results Anti-dsDNA was an insensitive (30%) but specific (>95%) marker for SLE. Levels of EC4d, BC4d, and PC4d were several times higher, and levels of ECR1 lower, in SLE patients compared to patients with other rheumatic diseases and healthy subjects. Among 523 anti-dsDNA-negative subjects, multivariate logistic regression analysis revealed that SLE was associated with ANA positivity (≥20 units), anti-MCV negativity (≤70 units), and elevated levels of both EC4d and BC4d (AUC 0.918, P < 0.001). A positive index score corresponding to the weighted sum of these 4 markers correctly categorized 72% of SLE patients. Specificity in relation to patients with other rheumatic diseases and healthy controls was >90%. The combination of anti-dsDNA and index score positivity yielded 80% sensitivity for SLE and 87% specificity against other rheumatic diseases. Conclusion An assay panel combining anti-dsDNA, ANA, anti-MCV, EC4d, and BC4d is sensitive and specific for the diagnosis of SLE. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) patients have a striking increase in cardiovascular (CV) comorbidity not fully explained by the Framingham risk score. Recent evidence from in vitro studies suggests that type I interferons (IFN) could promote premature CV disease (CVD) in SLE. We assessed the association of type I IFN signatures with functional and anatomical evidence of vascular damage, and with biomarkers of CV risk in a cohort of lupus patients without overt CVD. Methodology/Principal Findings: Serum type I IFN activity (induction of five IFN-inducible genes; IFIGs) from 95 SLE patient and 38 controls was quantified by real-time PCR. Flow mediated dilatation (FMD) of the brachial artery and carotid intima media thickness (CIMT) were quantified by ultrasound, and coronary calcification by computed tomography. Serum vascular biomarkers were measured by ELISA. We evaluated the effect of type I IFNs on FMD, CIMT and coronary calcification by first applying principal components analysis to combine data from five IFIGs into summary components that could be simultaneously modeled. Three components were derived explaining 97.1% of the total IFIG variation. Multivariable linear regression was utilized to investigate the association between the three components and other covariates, with the outcomes of FMD and CIMT; zero-inflated Poisson regression was used for modeling of coronary calcification. After controlling for traditional CV risk factors, enhanced serum IFN activity was significantly associated with decreased endothelial function in SLE patients and controls (p,0.05 for component 3), increased CIMT among SLE patients (p<0.01 for components 1 and 2), and severity of coronary calcification among SLE patients (p<0.001 for component 3). Conclusions: Type I IFNs are independently associated with atherosclerosis development in lupus patients without history of overt CVD and after controlling for Framingham risk factors. This study further supports the hypothesis that type I IFNs promote premature vascular damage in SLE. [ABSTRACT FROM AUTHOR]