Latent Tuberculosis Screening Among New Users of a Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drug: Gaps in Screening Overall and Among Janus Kinase Inhibitors.

OBJECTIVE: We combined claims and electronic health record (EHR) data to provide contemporary and accurate estimates of latent tuberculosis (TB) screening among new users of a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) and assess potential gaps in testing by drug type, patient characteristics, and practice. METHODS: Our denominator population was patients in the Rheumatology Informatics System for Effectiveness (RISE) registry and Medicare using a b/tsDMARD in 2018 without a claim or prescription in the year prior. TB screening was assessed in both Medicare and RISE 1 and 3 years before the medication start date. We calculated the proportion screened overall, by medication class, and by practice. We tested for demographic differences in screening using logistic regression. RESULTS: In the year before drug starts, 65.6% of patients had any TB screening; in a 3-year window, 72.9% had any TB screening. Rates of screening within 1 year by drug type were greater or equal to the overall screening rate for most drugs except for JAK inhibitors (JAKis) (46%) and interleukin-17 inhibitors (IL-17is) (11.5%). A lower proportion of Hispanic and Asian patients were screened compared with White patients. Practice screening rates ranged from 20.0% to 92.9% of patients within 1 year. CONCLUSION: We report higher screening rates than have previously been published because of combining claims and EHR data. However, important safety gaps remain, namely, reduced screening among new users of a JAKi or IL-17i and among Asian and Hispanic patients, as well as low-performing practices. Educational initiatives, team-based care delivery, task shifting, and technological interventions to address observed gaps in patient safety procedures are needed.

Incidence Rate and Factors Associated With Fractures Among Medicare Beneficiaries With Ankylosing Spondylitis in the United States.

OBJECTIVE: We evaluated the incidence rate and factors associated with fractures among adults with ankylosing spondylitis (AS). METHODS: We performed a retrospective cohort study with data from the Rheumatology Informatics System for Effectiveness registry linked to Medicare claims from 2016 to 2018. Patients were required to have two AS International Classification of Diseases codes 30 or more days apart and a subsequent Medicare claim. Then, 1 year of baseline characteristics were included, after which patients were observed for fractures. First, we calculated the incidence rate of fractures. Second, we constructed logistic regression models to identify factors associated with the fracture, including age, sex, race and ethnicity, body mass index, Medicare/Medicaid dual eligibility, area deprivation index, Charlson comorbidity index, smoking status, osteoporosis, historical fracture, and use of osteoporosis treatment, glucocorticoids, and opioids. RESULTS: We identified 1,426 adults with prevalent AS. Mean ± SD age was 69.4 ± 9.8 years, 44.3% were female, and 77.3% were non-Hispanic White. Fractures occurred in 197 adults with AS. The overall incidence rate of fractures was 76.7 (95% confidence interval [CI] 66.4-88.6) per 1,000 person-years. Older age (odds ratio [OR] 2.8, 95% CI 1.39-5.65), historical fracture (OR 5.24, 95% CI 3.44-7.99), and use of more than 30 mg morphine equivalent (OR 1.86, 95% CI 1.08-3.19) conferred increased odds of fracture. CONCLUSIONS: In this large sample of Medicare beneficiaries with AS, increasing age, historical fracture, and use of opioids had higher odds of fracture. Men and women were equally likely to have a fracture. Because opioid use was associated with fracture in AS, this high-risk population should be considered for interventions to mitigate risk.

Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis.

Diabetes mellitus (DM) has been proposed to be positively associated with breast cancer (BCa) risk due to shared risk factors, metabolic dysfunction, and the use of antidiabetic medications. We conducted a systematic review and meta-analysis to evaluate the association between DM and BCa risk. We searched PubMed, Embase, and Web of Science for cohort and case-control studies assessing the association between DM and BCa published before 10 December 2021. Two reviewers independently screened the studies for inclusion, abstracted article data, and rated study quality. Random effects models were used to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). From 8396 articles identified in the initial search, 70 independent studies were included in the meta-analysis. DM was associated with an overall increased risk of BCa (RR = 1.20, 95% CI: 1.11-1.29). The 24 case-control studies demonstrated a stronger association (RR = 1.26, 95% CI: 1.13-1.40) than the 46 cohort studies (RR = 1.15, 95% CI: 1.05-1.27). Studies reporting risk by menopausal status found that postmenopausal women had an elevated risk of developing BCa (RR = 1.12, 95% CI: 1.07-1.17). No association between DM and BCa risk was observed among premenopausal women (RR = 0.95, 95% CI: 0.85-1.05). In addition, DM was associated with significantly increased risks of oestrogen receptor (ER)+ (RR = 1.09, 95% CI: 1.00-1.20), ER- (RR = 1.16, 95% CI: 1.04-1.30), and triple negative BCa (RR = 1.41, 95% CI: 1.01-1.96). The association estimate for human epidermal growth factor 2-positive BCa was also positive (RR = 1.21, 95% CI: 0.52-2.82), but the CI was wide and crossed the null. Our meta-analysis confirms a modest positive association between DM and BCa risk. In addition, our results suggest that the association between DM and BCa may be modified by menopausal status, and that DM may be differentially associated with BCa subtypes defined by receptor status. Additional studies are warranted to investigate the mechanisms underlying these associations and any influence of DM on BCa receptor expression.

Peer Support in Rheumatic Diseases: A Narrative Literature Review.

Rheumatic diseases are a group of chronic conditions that are associated with significant morbidity, impaired physical function, psychosocial stress, and cost to the healthcare system. Peer support interventions have been shown to have a positive impact on health outcomes in several chronic conditions, but no review has specifically assessed the impact of peer support on rheumatic conditions. The aim of this narrative literature review was to understand how peer support has been applied in the field of rheumatology, with a specific focus on the impact of observational and randomized studies of direct peer support interventions on various outcome measures across rheumatic conditions. We also examined studies exploring patient attitudes and preferences toward peer support. The majority of studies included focused on peer support in rheumatoid arthritis and systemic lupus erythematosus. Generally, patients across the spectrum of rheumatic disease perceive peer support as a useful tool. Peer support interventions, while highly variable, were generally associated with positive impacts on health-related quality of life metrics (both perceived and measured), although these differences were not always statistically significant. Important limitations include variability in study design, selection bias among study participants, and short follow-up periods across most peer support interventions.

Association between self-reported race and ethnicity and myositis-specific autoantibodies in a diverse cohort of patients with inflammatory myopathy.

Myositis-specific autoantibodies (MSAs) are highly specific biomarkers for idiopathic inflammatory myopathies (IIMs). We investigated whether self-reported race and ethnicity were associated with the presence of specific MSAs. Charts of patients with IIM seen at 3 large healthcare systems in the same US city were reviewed. Demographic data and MSA test results were abstracted. Associations between race and ethnicity and presence of MSAs were analyzed using bivariate analysis and further characterized using separate unadjusted and adjusted logistic regression models. One hundred twenty-one subjects were included (19% Asian, 10% Black or African American, 27% Latinx or Hispanic, 36% non-Hispanic White, and 7% Other). In a bivariate analysis, anti-Jo-1 and anti-MDA5 autoantibodies were associated with race and ethnicity (p = 0.03 and 0.02, respectively). Black or African American subjects had increased odds of a positive anti-Jo-1 result compared to non-Hispanic White subjects on unadjusted logistic regression analysis (OR 8.61, 95% CI 1.61-46.07), although after adjustment for age and gender this finding was not significant. Subjects categorized as Other had increased odds of a positive anti-MDA5 result compared to non-Hispanic White subjects on both unadjusted (OR 55.0, 95% CI 2.02-1493) and adjusted analyses (OR 44.8, 95% CI 1.55-1298). Anti-Jo-1 and anti-MDA5 autoantibodies were significantly associated with race and ethnicity on bivariate analysis. Black or African American subjects had increased odds of positive anti-Jo-1 autoantibody on unadjusted, but not adjusted, logistic regression analysis. Subjects characterized as Other had increased odds of positive anti-MDA5 autoantibody, although confidence intervals were wide. Key Points • Association found between MSAs and race and ethnicity in diverse US cohort • Anti-Jo-1 and anti-MDA5 associated with race and ethnicity in bivariate analyses.

Diabetes mellitus and risk of breast cancer: a large-scale, prospective, population-based study.

BACKGROUND: The objective of this study was to evaluate associations of diabetes overall, type 1 diabetes (T1D), and type 2 diabetes (T2D) with breast cancer (BCa) risk. METHODS: We included 250,312 women aged 40-69 years between 2006 and 2010 from the UK Biobank cohort. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated for associations of diabetes and its two major types with the time from enrollment to incident BCa. RESULTS: We identified 8182 BCa cases during a median follow-up of 11.1 years. We found no overall association between diabetes and BCa risk (aHR = 1.02, 95% CI = 0.92-1.14). When accounting for diabetes subtype, women with T1D had a higher risk of BCa than women without diabetes (aHR = 1.52, 95% CI = 1.03-2.23). T2D was not associated with BCa risk overall (aHR = 1.00, 95% CI = 0.90-1.12). However, there was a significantly increased risk of BCa in the short time window after T2D diagnosis. CONCLUSIONS: Though we did not find an association between diabetes and BCa risk overall, an increased risk of BCa was observed shortly after T2D diagnosis. In addition, our data suggest that women with T1D may have an increased risk of BCa.

Development of American College of Rheumatology Quality Measures for Systemic Lupus Erythematosus: A Modified Delphi Process With Rheumatology Informatics System for Effectiveness (RISE) Registry Data Review.

OBJECTIVE: We aimed to develop readily measurable digital quality measure statements for clinical care in systemic lupus erythematosus (SLE) using a multistep process guided by consensus methods. METHODS: Using a modified Delphi process, an American College of Rheumatology (ACR) workgroup of SLE experts reviewed all North American and European guidelines from 2000 to 2020 on treatment, monitoring, and phenotyping of patients with lupus. Workgroup members extracted quality constructs from guidelines, rated these by importance and feasibility, and generated evidence-based quality measure statements. The ACR Rheumatology Informatics System for Effectiveness (RISE) Registry was queried for measurement data availability. In 3 consecutive Delphi sessions, a multidisciplinary Delphi panel voted on the importance and feasibility of each statement. Proposed measures with consensus on feasibility and importance were ranked to identify the top 3 measures. RESULTS: Review of guidelines and distillation of 57 quality constructs resulted in 15 quality measure statements. Among these, 5 met high consensus for importance and feasibility, including 2 on treatment and 3 on laboratory monitoring measures. The 3 highest-ranked statements were recommended for further measure specification as SLE digital quality measures: 1) hydroxychloroquine use, 2) limiting glucocorticoid use >7.5 mg/day to <6 months, and 3) end-organ monitoring of kidney function and urine protein excretion at least every 6 months. CONCLUSION: The Delphi process selected 3 quality measures for SLE care on hydroxychloroquine, glucocorticoid reduction, and kidney monitoring. Next, measures will undergo specification and validity testing in RISE and US rheumatology practices as the foundation for national implementation and use in quality improvement programs.

An Electronic Dashboard to Improve Dosing of Hydroxychloroquine Within the Veterans Health Care System: Time Series Analysis.

BACKGROUND: Hydroxychloroquine (HCQ) is commonly used for patients with autoimmune conditions. Long-term use of HCQ can cause retinal toxicity, but this risk can be reduced if high doses are avoided. OBJECTIVE: We developed and piloted an electronic health record-based dashboard to improve the safe prescribing of HCQ within the Veterans Health Administration (VHA). We observed pilot facilities over a 1-year period to determine whether they were able to improve the proportion of patients receiving inappropriate doses of HCQ. METHODS: Patients receiving HCQ were identified from the VHA corporate data warehouse. Using PowerBI (Microsoft Corp), we constructed a dashboard to display patient identifiers and the most recent HCQ dose and weight (flagged if ≥5.2 mg/kg/day). Six VHA pilot facilities were enlisted to test the dashboard and invited to participate in monthly webinars. We performed an interrupted time series analysis using synthetic controls to assess changes in the proportion of patients receiving HCQ ≥5.2 mg/kg/day between October 2020 and November 2021. RESULTS: At the start of the study period, we identified 18,525 total users of HCQ nationwide at 128 facilities in the VHA, including 1365 patients at the 6 pilot facilities. Nationwide, at baseline, 19.8% (3671/18,525) of patients were receiving high doses of HCQ. We observed significant improvements in the proportion of HCQ prescribed at doses ≥5.2 mg/kg/day among pilot facilities after the dashboard was deployed (-0.06; 95% CI -0.08 to -0.04). The difference in the postintervention linear trend for pilot versus synthetic controls was also significant (-0.06; 95% CI -0.08 to -0.05). CONCLUSIONS: The use of an electronic health record-based dashboard reduced the proportion of patients receiving higher than recommended doses of HCQ and significantly improved performance at 6 VHA facilities. National roll-out of the dashboard will enable further improvements in the safe prescribing of HCQ.

Spectrum of Clinical Presentations, Imaging Findings, and HLA Types in Immune Checkpoint Inhibitor-Induced Hypophysitis.

Context: Hypophysitis is a known immune-related adverse event (irAE) of immune checkpoint inhibitors (CPIs), commonly associated with CTLA-4 inhibitors and less often with PD-1/PD-L1 inhibitors. Objective: We aimed to determine clinical, imaging, and HLA characteristics of CPI-induced hypophysitis (CPI-hypophysitis). Methods: We examined the clinical and biochemical characteristics, magnetic resonance imaging (MRI) of the pituitary, and association with HLA type in patients with CPI-hypophysitis. Results: Forty-nine patients were identified. Mean age was 61.3 years, 61.2% were men, 81.6% were Caucasian, 38.8% had melanoma, and 44.5% received PD-1/PD-L1 inhibitor monotherapy while the remainder received CTLA-4 inhibitor monotherapy or CTLA-4/PD-1 inhibitor combination therapy. A comparison of CTLA-4 inhibitor exposure vs PD-1/PD-L1 inhibitor monotherapy revealed faster time to CPI-hypophysitis (median 84 vs 185 days, P < .01) and abnormal pituitary appearance on MRI (odds ratio 7.00, P = .03). We observed effect modification by sex in the association between CPI type and time to CPI-hypophysitis. In particular, anti-CTLA-4 exposed men had a shorter time to onset than women. MRI changes of the pituitary were most common at the time of hypophysitis diagnosis (55.6% enlarged, 37.0% normal, 7.4% empty or partially empty) but persisted in follow-up (23.8% enlarged, 57.1% normal, 19.1% empty or partially empty). HLA typing was done on 55 subjects; HLA type DQ0602 was over-represented in CPI-hypophysitis relative to the Caucasian American population (39.4% vs 21.5%, P = 0.01) and CPI population. Conclusion: The association of CPI-hypophysitis with HLA DQ0602 suggests a genetic risk for its development. The clinical phenotype of hypophysitis appears heterogenous, with differences in timing of onset, changes in thyroid function tests, MRI changes, and possibly sex related to CPI type. These factors may play an important role in our mechanistic understanding of CPI-hypophysitis.

Practical Considerations for Developing Clinical Natural Language Processing Systems for Population Health Management and Measurement.

Experts have noted a concerning gap between clinical natural language processing (NLP) research and real-world applications, such as clinical decision support. To help address this gap, in this viewpoint, we enumerate a set of practical considerations for developing an NLP system to support real-world clinical needs and improve health outcomes. They include determining (1) the readiness of the data and compute resources for NLP, (2) the organizational incentives to use and maintain the NLP systems, and (3) the feasibility of implementation and continued monitoring. These considerations are intended to benefit the design of future clinical NLP projects and can be applied across a variety of settings, including large health systems or smaller clinical practices that have adopted electronic medical records in the United States and globally.

Screening for Latent Infections Among Users of High-Risk Immunosuppressants: A Cross-Sectional Analysis From the Veterans Health Administration Healthcare System.

OBJECTIVES: Guidelines recommend screening for latent hepatitis B virus (HBV), hepatitis C virus (HCV), and tuberculosis (TB) before initiating biologics or targeted synthetic disease-modifying antirheumatic drugs (b/ts DMARDs) to avoid reactivation of life-threatening infections. The extent to which such screening occurs in the national Veterans Health Administration (VA) healthcare system is unknown. METHODS: Using data from the Veterans Affairs' (VA) Corporate Data Warehouse, we performed a cross-sectional analysis of veterans receiving b/ts DMARDs between October 1, 2017, and September 30, 2019. We calculated the proportion of patients with screening completed for latent HBV, HCV, and TB between October 1, 1999 and September 30, 2019. Patient characteristics associated with complete screening were evaluated using mixed-effects multivariate logistic regression models. We also examined facility-level factors associated with high versus lower performance. RESULTS: A total of 51,764 unique patients from 129 VA facilities received b/ts DMARDs from 2017 to 2019. Of these, 63% had complete screening. Among the 11,006 patients identified as new users, 64% had complete screening. Higher screening rates were observed among Hispanic/Latinx and Black/African American patients, users of B-cell therapies, and patients who had seen oncology subspecialists. Substantial variation was observed across facilities, with complete screening ranging from 13% to 98% of patients. Higher screening rates were associated with highly complex, urban, and higher-volume facilities. CONCLUSIONS: Approximately two-thirds of veterans taking b/ts DMARDs have received guideline-recommended screening for HBV, HCV, and TB, but substantial facility variation was observed. Performance measures, robust multidisciplinary workflows, and electronic health record-based tools to feed information back to providers may improve screening rates for low-performing facilities.

Development of a Natural Language Processing System for Extracting Rheumatoid Arthritis Outcomes From Clinical Notes Using the National Rheumatology Informatics System for Effectiveness Registry.

OBJECTIVE: To accelerate the use of outcome measures in rheumatology, we developed and evaluated a natural language processing (NLP) pipeline for extracting these measures from free-text outpatient rheumatology notes within the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry. METHODS: We included all patients in RISE (2015-2018). The NLP pipeline extracted scores corresponding to 8 measures of rheumatoid arthritis (RA) disease activity (DA) and functional status (FS) documented in outpatient rheumatology notes. Score extraction performance was evaluated by chart review, and we assessed agreement with scores documented in structured data. We conducted an external validation of our NLP pipeline using data from rheumatology notes from an academic medical center that is not included in the RISE registry. RESULTS: We processed over 34 million notes from 854,628 patients, 158 practices, and 24 electronic health record (EHR) systems from RISE. Manual chart review revealed a sensitivity, positive predictive value (PPV), and F1 score of 95%, 87%, and 91%, respectively. Substantial agreement was observed between scores extracted from RISE notes and scores derived from structured data (κ = 0.43-0.68 among DA and 0.86-0.98 among FS measures). In the external validation, we found a sensitivity, PPV, and F1 score of 92%, 69%, and 79%, respectively. CONCLUSION: We developed an NLP pipeline to extract RA outcome measures from a national registry of notes from multiple EHR systems and found it to have good internal and external validity. This pipeline can facilitate measurement of clinical- and patient-reported outcomes for use in research and quality measurement.

Frequency of Contraception Documentation in Women With Systemic Lupus Erythematosus and Rheumatoid Arthritis Within the Rheumatology Informatics System for Effectiveness Registry.

OBJECTIVE: We sought to understand the frequency of contraception documentation for women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in a large US electronic health record (EHR)-based registry and to identify disparities by teratogen prescription and patient race and ethnicity. METHODS: Contraception documentation from structured data fields within the Rheumatology Informatics System for Effectiveness (RISE) registry was collected for women of childbearing age (18-45 years) in 2018 who had at least 2 visits with International Classification of Diseases, Ninth Revision or Tenth Revision, diagnosis codes for SLE or RA (at any time). Univariate and multivariate analyses compared the frequency of contraception documentation based on patient characteristics including diagnosis, age, race, and teratogenicity of prescribed antirheumatic medications. RESULTS: In 2018, there were 9,826 women of childbearing age with SLE and 19,009 with RA, of whom 9.1% had any contraception documented. Rates of contraceptive documentation were significantly lower for women with SLE (adjusted odds ratio [OR] 0.84 [95% confidence interval (95% CI) 0.76-0.92]). Women of Hispanic ethnicity and Black and Asian race were all less likely than White women to have contraception documentation. Teratogen prescription was associated with higher rates of contraception documentation for women with RA but not SLE (RA adjusted OR 1.31 [95% CI 1.16-1.47]; SLE adjusted OR 1.08 [95% CI 0.91-1.28]). CONCLUSION: There are large gaps in contraception documentation within the RISE registry that are particularly stark among women of color. Although these data likely underestimate contraception use, they highlight that most rheumatologists do not have a systematic approach to collecting and recording this information in the EHR.

Monitoring and Achievement of Target Serum Urate Among Gout Patients Receiving Long-Term Urate-Lowering Therapy in the American College of Rheumatology RISE Registry.

OBJECTIVE: The American College of Rheumatology's (ACR) 2020 guidelines for the management of gout recommend using a treat-to-target approach to lower serum urate (SU). Using the ACR's Rheumatology Informatics System for Effectiveness registry, we examined the use of a treat-to-target approach among gout patients receiving long-term urate-lowering therapy (ULT) and followed longitudinally by rheumatologists. METHODS: Included patients had one or more diagnoses for gout in 2018-2019 and continuous use of ULT for ≥12 months. We assessed the proportions of patients with SU monitoring and, among those tested, who achieved SU <6.0 mg/dl during the measurement year. Multilevel logistic regression adjusting for sociodemographics, comorbidities, region, and health care utilization was used to determine factors associated with SU monitoring and achievement of target SU. RESULTS: A total of 9,560 were included. The mean ± SD age was 67.2 ± 12.7 years, 73.5% of patients were male, and 32.3% were non-White. Fifty-six percent of patients had at least 1 SU recorded during the measurement year; among patients with at least 1 SU recorded, 74% achieved the SU target. In multivariate analyses, non-White patients were slightly less likely to be tested or achieve a target SU. CONCLUSION: Among gout patients receiving long-term ULT followed longitudinally by rheumatologists, more than half had a documented SU, and among those tested, three-quarters achieved the recommended SU target. Routine monitoring of SU is a first step toward improving quality of care for patients with gout.

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.

Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study.

Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 µg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14). Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities. Funding: American College of Rheumatology and European Alliance of Associations for Rheumatology.

Evaluating the Use of Glucocorticoids Among Belimumab-Treated Patients With Systemic Lupus Erythematosus in Real-World Settings Using the Rheumatology Informatics System for Effectiveness Registry.

OBJECTIVE: Glucocorticoids are part of standard therapy for systemic lupus erythematosus (SLE), despite adverse effects associated with long-term treatment. Belimumab improved clinical manifestations of SLE and reduced glucocorticoid doses in clinical trials and clinical practice; however, associations have not been examined using multi-institutional electronic health record (EHR) data. Using the Rheumatology Informatics System for Effectiveness registry, we examined glucocorticoid use patterns among belimumab-treated adults with SLE. METHODS: This retrospective analysis (GSK Study 209267) used EHR prescription records of patients with SLE managed by rheumatologists. Eligible patients had an index date (first belimumab prescription) between January 2014 and June 2018. The primary analysis compared patients' mean daily oral glucocorticoid (prednisone equivalent) dose over the 6 months preindex versus 6 months post index. An exploratory analysis assessed glucocorticoid doses at 12 and 24 months post index for patients with extended follow-up. RESULTS: Of the 1987 patients receiving their first belimumab prescription, 767 had available glucocorticoid prescribing data, whereas 204 (primary analysis population) had glucocorticoids prescribed in the 6 months preindex and received belimumab according to the prescribing information for the first 8 weeks post index. The mean (SD) glucocorticoid dose was 12.5 (13.5) mg/day 3 months preindex, reducing to 10.3 (10.6) mg/day over the 6 months post index, and 8.7 (9.4) and 9.0 (9.3) mg/day at 12 and 24 months post index. CONCLUSION: This study showed reductions in mean daily glucocorticoid dose after belimumab initiation. Several limitations of EHRs for real-world effectiveness research were identified, which limited interpretation of results and may inform future study designs.