The impact of alternative arrangements, contingent jobs, and work secured through an app on the well-being of working age adults: Results from the California Work and Health Survey.

BACKGROUND: There is recognition of the growing prevalence of alternative work arrangements, contingent jobs, and work secured through an app. However, there have been few systematic efforts to understand the impact of these forms of work on individuals and households. METHODS: The data derive from the California Work and Health Survey administered to a sample of the working age population of the state solicited through random-digit dialing of cell phone numbers. 4014 individuals completed the survey, 26% of those with an in-service cell phone number. We present odds ratios and 95% confidence intervals from logistic regression estimating the impact of being an independent contractor, in other forms of alternative work arrangements, in contingent jobs, and in work secured through an app, on economic and health status and working conditions in main jobs, with and without adjustment for covariates. RESULTS: Several of the forms of work analyzed are associated with lower earnings and higher rates of wage theft, household poverty, benefit recipiency, and expectation of hardships in food, housing, and medical care in the immediate future. Association between the forms of work and current health status is less consistent. However, several forms of work are associated with working conditions known to be risk factors for subsequent health problems. CONCLUSIONS: Public policy to mitigate the adverse impacts of work, largely developed in the 20th Century when there was an identified workplace, may be insufficient to protect workers' well-being for alternative work arrangements, contingent jobs, and work secured through an app.

Positive psychosocial factors may protect against perceived stress in people with systemic lupus erythematosus with and without trauma history.

OBJECTIVE: Trauma history is associated with SLE onset and worse patient-reported outcomes; perceived stress is associated with greater SLE disease activity. Stress perceptions vary in response to life events and may be influenced by psychosocial factors. In an SLE cohort, we examined whether stressful events associated with perceived stress, whether psychosocial factors affected perceived stress, and whether these relationships varied by prior trauma exposure. METHODS: This is a cross-sectional analysis of data from the California Lupus Epidemiology Study, an adult SLE cohort. Multivariable linear regression analyses controlling for age, gender, educational attainment, income, SLE damage, comorbid conditions, glucocorticoids ≥7.5 mg/day and depression examined associations of recent stressful events (Life Events Inventory) and positive (resilience, self-efficacy, emotional support) and negative (social isolation) psychosocial factors with perceived stress. Analyses were stratified by lifetime trauma history (Brief Trauma Questionnaire (BTQ)) and by adverse childhood experiences (ACEs) in a subset. RESULTS: Among 242 individuals with SLE, a greater number of recent stressful events was associated with greater perceived stress (beta (95% CI)=0.20 (0.07 to 0.33), p=0.003). Positive psychosocial factor score representing resilience, self-efficacy and emotional support was associated with lower perceived stress when accounting for number of stressful events (-0.67 (-0.94 to -0.40), p<0.0001); social isolation was associated with higher stress (0.20 (0.14 to 0.25), p<0.0001). In analyses stratified by BTQ trauma and ACEs, associations of psychosocial factors and perceived stress were similar between groups. However, the number of recent stressful events was significantly associated with perceived stress only for people with BTQ trauma (0.17 (0.05 to 0.29), p=0.0077) and ACEs (0.37 (0.15 to 0.58), p=0.0011). CONCLUSION: Enhancing positive and lessening negative psychosocial factors may mitigate deleterious perceived stress, which may improve outcomes in SLE, even among individuals with a history of prior trauma who may be more vulnerable to recent stressful events.

Screening of Environmental Chemicals to Characterize Exposures in Participants With Systemic Lupus Erythematosus.

OBJECTIVE: There is a need to characterize exposures associated with the pathogenesis of systemic lupus erythematosus (SLE). In this pilot study, we explore a hypothesis-free approach that can measure thousands of exogenous chemicals in blood ("exposome") in patients with SLE and unaffected controls. METHODS: This cross-sectional study analyzed a cohort of patients with prevalent SLE (n = 285) and controls (n = 106). Plasma was analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Mass spectrometry features present in at least 25% of all samples were selected for association analysis (n = 2,737). Features were matched to potential chemicals using available databases. Association analysis of abundances of features with SLE status was performed, adjusting for age and sex. We also explored features associated with SLE phenotypes, sociodemographic factors, and current medication use. RESULTS: We found 30 features significantly associated with SLE status (Bonferroni P < 0.05). Of these, seven matched chemical names based on databases. These seven features included phthalate metabolites, a formetanate metabolite, and eugenol. The abundance of acid pesticides differed between patients with SLE and controls (Bonferroni P < 0.05). Two unmatched features were associated with a history of lupus nephritis, and one with anti-double-stranded DNA antibody production (Bonferroni P < 0.05). Seventeen features varied by self-reported race and ethnicity, including a polyfluoroalkyl substance (analysis of variance P < 1.69 × 10-5). Eleven features correlated with antimalarials, 6 with mycophenolate mofetil, and 29 with prednisone use. CONCLUSION: This proof-of-concept study demonstrates that LC-QTOF/MS is a powerful tool that agnostically detects circulating exogenous compounds. These analyses can generate hypotheses of disease-related exposures for future prospective, longitudinal studies.

Race, Ethnicity, and Disparities in the Risk of End-Organ Lupus Manifestations Following a Systemic Lupus Erythematosus Diagnosis in a Multiethnic Cohort.

OBJECTIVE: Data on the onset of lupus manifestations across multiple organ domains and in diverse populations are limited. The objective was to analyze racial and ethnic differences in the risk of end-organ lupus manifestations following systemic lupus erythematosus (SLE) diagnosis in a multiethnic cohort. METHODS: The California Lupus Epidemiology Study (CLUES) is a longitudinal study of SLE. Data on major end-organ lupus manifestations were collected and categorized by organ system: renal, hematologic, neurologic, cardiovascular, and pulmonary. Multiorgan disease was defined as manifestations in ≥2 of these distinct organ systems. Kaplan-Meier curves assessed end-organ disease-free survival, and Cox proportional hazards regression estimated the rate of end-organ disease following SLE diagnosis, adjusting for age at diagnosis, sex, and self-reported race and ethnicity (White, Hispanic, Black, and Asian). RESULTS: Of 326 participants, 89% were female; the mean age was 45 years. Self-reported race and ethnicity were 30% White, 23% Hispanic, 11% Black, and 36% Asian. Multiorgan disease occurred in 29%. Compared to White participants, Hispanic and Asian participants had higher rates, respectively, of renal (hazard ratio [HR] 2.9 [95% confidence interval (95% CI) 1.8-4.7], HR 2.9 [95% CI 1.9-4.6]); hematologic (HR 2.7 [95% CI 1.3-5.7], HR 2.1 [95% CI 1.0-4.2]); and multiorgan disease (HR 3.3 [95% CI 1.8-5.9], HR 2.5 [95% CI 1.4-4.4]) following SLE diagnosis. CONCLUSION: We found heightened risks of developing renal, hematologic, and multiorgan disease following SLE diagnosis among Hispanic and Asian patients with SLE, as well as a high burden of multiorgan disease among CLUES participants.

Causes of Death Among Individuals With Systemic Lupus Erythematosus by Race and Ethnicity: A Population-Based Study.

OBJECTIVE: Non-White populations are at higher risk of developing systemic lupus erythematosus (SLE) and have more severe outcomes, including mortality. The present study was undertaken to examine how specific causes of death vary by race and ethnicity, including Asian and Hispanic individuals. METHODS: The California Lupus Surveillance Project included SLE cases identified among residents of San Francisco County, CA during January 1, 2007 to December 31, 2009. Cases were matched to the National Death Index over a 10-year period. Logistic regression examined age-adjusted differences in causes of death by race, ethnicity, and sex. Age-standardized mortality ratios between individuals with SLE and the corresponding general population were calculated for the leading cause of death, and observed versus expected deaths were estimated. RESULTS: The study included 812 individuals of White (38%), Asian (36%), Black (20%), and mixed/other/unknown (5%) race; 15% identified as Hispanic. One hundred thirty-five deaths were recorded, with a mean ± SD age at death of 62.2 ± 15.6 years. Cardiovascular disease (CVD) was the leading cause of death overall (33%), and across all racial and ethnic groups, followed by rheumatic disease (18%) and hematologic/oncologic conditions (18%). CVD as the underlying cause of death was 3.63 times higher among SLE cases than in the general population. CVD deaths for those with SLE were nearly 4 and 6 times higher for Asian and Hispanic individuals with SLE, respectively, compared to the general population. CONCLUSION: Individuals with SLE experience a disproportionate burden of CVD mortality compared to the general population, which is magnified for Asian and Hispanic groups.

Perceived Stress and Prediction of Worse Disease Activity and Symptoms in a Multiracial, Multiethnic Systemic Lupus Erythematosus Cohort.

OBJECTIVE: Studies have suggested a potential link between traumatic experiences, psychological stress, and autoimmunity, but the impact of stress on disease activity and symptom severity in systemic lupus erythematosus (SLE) remains unclear. The present study was undertaken to examine whether increases in perceived stress independently associate with worse SLE disease outcomes over 3 years of follow-up. METHODS: Participants were drawn from the California Lupus Epidemiology Study (CLUES). Stress was measured annually using the 4-item Perceived Stress Scale (PSS). Participants with increases of ≥0.5 SD in PSS score were defined as having an increase in stress. Four outcomes were measured at the year 3 follow-up visit: physician-assessed disease activity (Systemic Lupus Erythematosus Disease Activity Index); patient-reported disease activity (Systemic Lupus Activity Questionnaire); pain (Patient-Reported Outcomes Measurement Information System [PROMIS] pain interference scale); and fatigue (PROMIS fatigue scale). Multivariable linear regression evaluated longitudinal associations of increase in stress with all 4 outcomes while controlling for potential confounders. RESULTS: The sample (n = 260) was 91% female, 36% Asian, 30% White, 22% Hispanic, and 11% African American; the mean ± SD age was 46 ± 14 years. In adjusted longitudinal analyses, increase in stress was independently associated with greater physician-assessed disease activity (P = 0.015), greater self-reported disease activity (P < 0.001), more pain (P = 0.019), and more fatigue (P < 0.001). CONCLUSION: In a racially diverse sample of individuals with SLE, those who experienced an increase in stress had significantly worse disease activity and greater symptom burden at follow-up compared to those with stress levels that remained stable or declined. Findings underscore the need for interventions to bolster stress resilience and support effective coping strategies among individuals living with lupus.

Assessment of Risk of Rheumatoid Arthritis Among Underground Hard Rock and Other Mining Industry Workers in Colorado, New Mexico, and Utah.

Importance: Respirable silica exposure has been strongly and consistently linked to rheumatoid arthritis (RA) among foundry workers, persons in the construction trades, stone crushers and drillers, and coal miners. However, risk of RA in hard rock mining has not been thoroughly investigated. Objective: To analyze occupational risk of RA in hard rock miners in Colorado, New Mexico, and Utah. Design, Setting, and Participants: This cross-sectional survey study estimated the association between mining industry work and reported RA in a random-digit telephone survey of men 50 years or older living in selected counties with elevated levels of pneumoconiosis mortality (N = 1988). The survey was conducted between January 12 and May 4, 2021. Exposures: Underground hard rock and other mining and related mineral-processing occupations. Main Outcomes and Measures: Report of a clinician diagnosis of RA further defined by treatment with corticosteroids or disease-modifying antirheumatic drugs. Risk was estimated using logistic regression. Results: The analytic sample of 1988 men (survey response rate, 11.1% of all contacts) had a mean (SD) age of 68.6 (10.1) years. Underground hard rock mining was reported by 118 (5.9%); underground mining of other types, predominantly coal mining (no concomitant hard rock), 62 (3.1%); and surface mining or ore processing (no underground), 262 (13.2%). Adjusting for age and smoking and accounting for nonmining silica exposure, mining employment was associated with increased odds of corticosteroid-treated RA (n = 89) (odds ratio, 4.12 [95%, 2.49-6.81]). The odds were similar for RA treated with disease-modifying antirheumatic drugs (n = 80) (odds ratio, 3.30 [95% CI, 1.93-5.66]). Conclusions and Relevance: In this cross-sectional survey study, workers in hard rock and other underground mining and surface mining occupations experienced 3- to 4-fold increased odds of RA. These findings suggest that clinicians should consider patients with relevant work exposures as at higher risk for developing RA.

Dynamics of Methylation of CpG Sites Associated With Systemic Lupus Erythematosus Subtypes in a Longitudinal Cohort.

OBJECTIVE: 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. METHODS: A total of 101 participants from the California Lupus Epidemiology Study were included in our analysis. DNA was extracted from blood samples collected at the time of enrolment in the cohort and samples collected after 2 years and was analyzed using Illumina EPIC BeadChip kit. Paired t-tests were used to identify genome-wide changes which included 256 CpG sites previously found to be associated with SLE subtypes. Linear mixed models were developed to understand the relationship between DNA methylation and disease activity, medication use, and sample cell-type proportions, adjusted for age, sex, and genetic principal components. RESULTS: The majority of CpGs that were previously determined to be associated with SLE subtypes remained stable over 2 years (185 CpGs [72.3%]; t-test false discovery rate >0.05). Compared to background genome-wide methylation, there was an enrichment of SLE subtype-associated CpGs that changed over time (27.7% versus 0.34%). Changes in cell-type proportions were associated with changes at 67 CpGs (P < 2.70 × 10-5 ), and 15 CpGs had at least 1 significant association with immunosuppressant use. CONCLUSION: In this longitudinal SLE cohort, we identified a subset of SLE subtype-associated CpGs that remained stable over time and may be useful as biomarkers of disease subtypes. Another subset of SLE subtype-associated CpGs changed at a higher proportion compared to the genome-wide methylome. Additional studies are needed to understand the etiology and impact of these changes on methylation of SLE-associated CpGs.

Low cumulative disease activity is associated with higher bone mineral density in a majority Latinx and Asian US rheumatoid arthritis cohort.

OBJECTIVE: Prior studies have found conflicting results when evaluating the association between rheumatoid arthritis (RA) disease activity and bone mineral density (BMD). Whether or not cumulative RA disease activity is associated with BMD remains unanswered. METHODS: Data were from the University of California San Francisco RA Cohort from years 2006-2018. Those with BMD measures and at least two study visits prior to BMD measure were included in the study. The association between low cumulative disease activity, as measured by DAS28ESR, with the primary outcome of femoral neck BMD was assessed using multivariable linear regression. Sensitivity analyses were performed substituting CDAI for the disease activity measure as well as total hip and lumbar spine BMD as outcomes. RESULTS: 161 participants with RA were studied. The cohort was 62.4 ± 10.2 years old and 88% female. Hispanic/Latino (N = 73, 45%) and Asian (N = 59, 37%) were the most common racial/ethnic groups in our cohort. Mean RA duration was 10.5 ± 7.3 years and 83% were ACPA positive. Low disease activity was independently associated with higher femoral neck BMD compared to the moderate/high disease activity group (ß= 0.071 [95%CI: 0.021 to 0.122], p = 0.020). The relationship between low cumulative disease activity was similar when CDAI and other BMD sites were substituted in the multivariable models. CONCLUSION: Low cumulative disease activity as measured by DAS28ESR was associated with higher femoral neck BMD, independent of traditional osteoporosis risk factors (e.g., age, sex, BMI) in a unique RA cohort. Results were similar when evaluating cumulative low CDAI and other BMD sites.

Dusty trades and associated rheumatoid arthritis in a population-based study in the coal mining counties of Appalachia.

OBJECTIVES: We previously showed increased coal mining-associated risk of rheumatoid arthritis (RA). Using additional survey data, we sought to delineate this risk further. METHODS: We used data from two cross-sectional, random-digit-dial, population-based surveys (males;≥50 years) in selected counties in the Appalachian region of the inland, mid-Atlantic USA with elevated pneumoconiosis mortality. Surveys ascertained age, smoking, coal mining and non-coal silica exposure jobs. In a subset, we surveyed ergonomic exposures, scored by intensity. We queried diagnosis of RA, corticosteroid use, and, in a subset, use of disease modifying antirheumatic drugs (DMARDs). Multivariable logistic regression modelled RA risk (defined by glucocorticoid or DMARDs use) associated with coal mining employment, other silica exposure, smoking status, and age and ergonomic exposures. RESULTS: We analysed data for 2981 survey respondents (mean age 66.6 years; 15% current, 44% ex-smokers). The prevalence of glucocorticoid-treated and DMARD-treated RA was 11% and 4%, respectively. Glucocorticoid-treated RA was associated with coal mining (OR 3.5; 95% CI 2.5 to 4.9) and non-coal mining silica exposure (OR 3.2; 95% CI 2.4 to 4.4). For DMARD-treated RA, the odds associated with coal mining and other silica remained elevated: OR 2.3 (95% CI 1.18, 4.5) and OR 2.7 (95% CI 1.51, 5.0), respectively. In the same model, the highest intensity ergonomic exposure also was associated with increased odds of RA (OR 4.3; 95% CI 1.96 to 9.6). CONCLUSIONS: We observed a strong association between coal mining and other silica-exposing dusty trades and RA. Clinicians and insurers should consider occupational histories in the aetiology of RA.

Physical Inactivity and Incident Depression in a Multiracial, Multiethnic Systemic Lupus Erythematosus Cohort.

OBJECTIVE: Physical activity is known to improve depressive symptoms. The present study was undertaken to examine physical inactivity as a predictor of incident depression in systemic lupus erythematosus (SLE). METHODS: Data derive from the California Lupus Epidemiology Study (CLUES), a longitudinal cohort with confirmed SLE diagnoses. Physical inactivity was assessed from a single item, "I rarely or never do any physical activities," and depressive symptoms by the 8-item Patient Health Questionnaire (PHQ-8). Analysis included those not depressed at baseline (PHQ-8 score <10) who completed an in-person baseline assessment and at least 1 follow-up visit (n = 225). Incident depression was defined as a PHQ-8 score of ≥10 at follow-up. Cox proportional hazards regression modeled incident depression over 2 years as a function of baseline physical inactivity, controlling for age, sex, race, income, comorbidities, disease activity, and disease damage. RESULTS: At baseline, the mean ± SD age of the participants was 45 ± 15 years, 88% were female, and 70% identified as non-White. Mean PHQ scores for those without depression at baseline did not differ by activity status, but those who were inactive at baseline were significantly more likely to develop depression over the next 2 years (hazard ratio [HR] 2.89 [95% confidence interval (95% CI) 1.46-5.71]). After adjusting for covariates, the association remained strong, including a >3-fold increased risk of incident depression among the sedentary group (HR 3.88 [95% CI 1.67-9.03]). CONCLUSION: In this diverse SLE cohort, a simple question about physical inactivity was highly predictive of incident depression over the subsequent 2 years. Results suggest an urgent need for approaches to reduce sedentary behavior in this high-risk population.

High Disease Severity Among Asian Patients in a US Multiethnic Cohort of Individuals With Systemic Lupus Erythematosus.

OBJECTIVE: Knowledge about systemic lupus erythematosus (SLE) outcomes among US Asian patients is lacking. The present study was undertaken to examine SLE disease activity, severity, and damage among Asian patients of primarily Chinese and Filipino descent in a multiethnic cohort. METHODS: California Lupus Epidemiology Study (n = 328) data were analyzed. Data were collected in English, Cantonese, Mandarin, or Spanish using validated instruments for disease activity (Systemic Lupus Erythematosus Disease Activity Index), disease severity (Lupus Severity Index [LSI]), and disease damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). We assessed differences in SLE outcomes among racial/ethnic groups using multivariable linear regression including interaction terms for age at diagnosis and race/ethnicity. RESULTS: Asian was the largest racial/ethnic group (38% [Chinese = 22%; Filipino = 9%; Other = 7%]). Average age at diagnosis was younger among Asian patients (27.9 years), particularly Filipino patients (22.2 years), compared with White (29.4 years) and Black patients (34.0 years). After adjustment, disease activity and damage were not significantly different across groups. Disease severity among Asian patients was significantly higher than among White patients (LSI score 7.1 versus 6.5; P < 0.05) but similar among Black and Hispanic patients. Early age at diagnosis was associated with greater organ damage among Asian, Black, and Hispanic patients, but not White patients. CONCLUSION: SLE was more severe among US Asian patients compared to White patients. Filipinos were affected at strikingly young ages. Asian patients and non-White groups with younger age at diagnosis had greater organ damage than White patients. Such racial/ethnic distinctions suggest the need for heightened clinical awareness to improve health outcomes among Asian patients with SLE. Further study of SLE outcomes across a range of US Asian subgroups is important.

Significant Gains in Rheumatoid Arthritis Quality Measures Among RISE Registry Practices.

OBJECTIVE: Using the American College of Rheumatology Rheumatology Informatics System for Effectiveness (RISE) registry, our objective was to examine performance on rheumatoid arthritis (RA) quality measures and to assess the association between practice characteristics and changes in performance over time among participating practices. METHODS: We analyzed data from practices enrolled in RISE between January 1, 2015 and December 31, 2017. Eight quality measures in the areas of RA disease management, cardiovascular risk reduction, and patient safety were examined. Variability in performance was evaluated at the practice level. Multivariate linear models were used to predict change in measure performance by year and to determine the effect of practice characteristics on change in performance over time. RESULTS: Data from 59,986 patients from 54 practices were examined. The mean ± SD age was 62 ± 14 years, 77% were female, 69% were Caucasian, and most patients were seen in a single-specialty group practice (46%). The average performance on measures related to RA treatments was consistently high (>90%) across the study period. Measures related to RA functional status and disease activity assessment had the greatest improvements over time (8.4% and 13.0% increase per year, respectively; P < 0.001). Single-specialty group practices had the fastest rates of improvement over time across all measures. CONCLUSION: Among practices participating in RISE between 2015 and 2017, performance on most RA quality measures improved. Single-specialty group practices saw the fastest rates of improvement over time. Identification of workflow patterns leading to dramatic improvements in quality of care will help guide process redesign to address gaps in priority areas, such as tuberculosis screening and blood pressure control.

Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.

Importance: Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective: To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. Design, Setting, and Participants: This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. Exposures: Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. Main Outcomes and Measures: The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. Results: A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. Conclusions and Relevance: In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.

Inorganic Dust Exposure During Military Service as a Predictor of Rheumatoid Arthritis and Other Autoimmune Conditions.

OBJECTIVE: Rheumatoid arthritis (RA) and other autoimmune (AI) conditions are associated with inorganic dust exposure. Many military activities are likely to entail inorganic dust exposures. We wished to identify associations between prior military dust exposure and RA and other AI conditions. METHODS: We studied persons from a roster of Army, Navy, Air Force, or Marine Corps personnel who had served in Operation Enduring Freedom and Operations Iraqi Freedom and New Dawn. We linked military occupational codes to a job exposure matrix assigning dust exposure likelihood. We used the Veterans Affairs Health Care System (VAHCS) electronic health care records to identify cases of RA, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), vasculitis, and inflammatory myositis. Generalized estimating equations modeled risk of RA and other AI conditions associated with dust exposure, taking into account military service branch, age at first VAHCS encounter, sex, race/ethnicity, smoking status, and years of military service. RESULTS: Of 438 086 veterans (68% ever-smokers), 44% were classified with likely or somewhat likely dust exposure. Cases included 1139 cases with RA, 467 cases with SLE, and 180 cases with other AI diseases (SSc, vasculitis, or inflammatory myositis). Military dust exposure was associated with increased odds of RA (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.003-1.20) and increased odds of SSc, vasculitis, or inflammatory myositis (OR = 1.23; 95% CI = 1.14-1.34) but was protective for SLE (OR = 0.81; 95% CI = 0.76-0.88). CONCLUSION: Dust exposure during past military service comprises an occupational and environmental risk factor for RA and other AI diseases. This is potentially relevant for prevention activities.

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry.

OBJECTIVE: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). METHODS: We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. RESULTS: Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. CONCLUSIONS: People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

Transcriptomic analysis of immune cells in a multi-ethnic cohort of systemic lupus erythematosus patients identifies ethnicity- and disease-specific expression signatures.

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.

The Impact of Asthma and Chronic Obstructive Pulmonary Disease (COPD) on Patient-Reported Outcomes in Systemic Lupus Erythematosus (SLE).

BACKGROUND: Risk of asthma and chronic obstructive pulmonary disease (COPD) may be elevated in systemic lupus erythematosus (SLE), but little research has studied the impact of these conditions on SLE outcomes. We examined prevalence, incidence, and impact of self-reported asthma and COPD in two US-based SLE cohorts (FORWARD and Lupus Outcomes Study [LOS]). METHODS: Prevalence of asthma and COPD were defined as presence of conditions at individuals' first interviews; incidence was defined as new reports over the next 3 years. Cross-sectional associations of asthma/COPD with patient-reported outcomes (PROs) and longitudinal analyses associations with asthma/COPD at entry with PROs 3 years later were examined. RESULTS: In FORWARD, 19.8% and 8.3% participants reported asthma and COPD, respectively, at entry. In LOS, 36.0% reported the presence of either (US population comparisons: asthma, 9.7%; COPD, 6.1%). Cross-sectionally, asthma/COPD was associated with worse PROs, including disease activity. In FORWARD, individuals with asthma experienced greater worsening of fatigue, pain, and global health ratings longitudinally; individuals with COPD experienced greater increases in self-reported SLE activity. However, no such patterns were noted in the LOS. CONCLUSION: Asthma and COPD appeared to be more common in SLE than in the general US population and were associated with worse status on PROs cross-sectionally. Asthma was linked to decrements in PROs longitudinally.