Impact of Risk Factors on COVID-19 Outcomes in Unvaccinated People With Rheumatic Diseases: A Comparative Analysis of Pandemic Epochs Using the COVID-19 Global Rheumatology Alliance Registry.

OBJECTIVE: Approximately one third of individuals worldwide have not received a COVID-19 vaccine. Although studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern. METHODS: Patients with RDs and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; subanalyses stratified patients according to RD types. RESULTS: Among 19,256 unvaccinated people with RDs and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell-depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B-cell-depleting therapy was associated with worse outcomes. CONCLUSION: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.

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.

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.

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.

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.

Association Between Race/Ethnicity and COVID-19 Outcomes in Systemic Lupus Erythematosus Patients From the United States: Data From the COVID-19 Global Rheumatology Alliance.

OBJECTIVE: To determine the association between race/ethnicity and COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE). METHODS: Individuals with SLE from the US with data entered into the COVID-19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID-19 severity, adjusting for possible confounders. RESULTS: We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36-5.53]) and Hispanic (OR 2.76 [95% CI 1.34-5.69]) individuals had higher odds of more severe outcomes than White individuals. CONCLUSION: Black and Hispanic individuals with SLE experienced more severe COVID-19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population.

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.

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.

Development of a Prediction Model for COVID-19 Acute Respiratory Distress Syndrome in Patients With Rheumatic Diseases: Results From the Global Rheumatology Alliance Registry.

OBJECTIVE: Some patients with rheumatic diseases might be at higher risk for coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). We aimed to develop a prediction model for COVID-19 ARDS in this population and to create a simple risk score calculator for use in clinical settings. METHODS: Data were derived from the COVID-19 Global Rheumatology Alliance Registry from March 24, 2020, to May 12, 2021. Seven machine learning classifiers were trained on ARDS outcomes using 83 variables obtained at COVID-19 diagnosis. Predictive performance was assessed in a US test set and was validated in patients from four countries with independent registries using area under the curve (AUC), accuracy, sensitivity, and specificity. A simple risk score calculator was developed using a regression model incorporating the most influential predictors from the best performing classifier. RESULTS: The study included 8633 patients from 74 countries, of whom 523 (6%) had ARDS. Gradient boosting had the highest mean AUC (0.78; 95% confidence interval [CI]: 0.67-0.88) and was considered the top performing classifier. Ten predictors were identified as key risk factors and were included in a regression model. The regression model that predicted ARDS with 71% (95% CI: 61%-83%) sensitivity in the test set, and with sensitivities ranging from 61% to 80% in countries with independent registries, was used to develop the risk score calculator. CONCLUSION: We were able to predict ARDS with good sensitivity using information readily available at COVID-19 diagnosis. The proposed risk score calculator has the potential to guide risk stratification for treatments, such as monoclonal antibodies, that have potential to reduce COVID-19 disease progression.

SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease: results from the COVID-19 Global Rheumatology Alliance provider registry.

OBJECTIVE: While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2. METHODS: We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes. RESULTS: SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died. CONCLUSION: More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.

Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance.

AIM: To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19. METHODS: People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity. RESULTS: A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab. CONCLUSIONS: More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

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.

The Relationship Between Electronic Health Record System and Performance on Quality Measures in the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) Registry: Observational Study.

BACKGROUND: Routine collection of disease activity (DA) and patient-reported outcomes (PROs) in rheumatoid arthritis (RA) are nationally endorsed quality measures and critical components of a treat-to-target approach. However, little is known about the role electronic health record (EHR) systems play in facilitating performance on these measures. OBJECTIVE: Using the American College Rheumatology's (ACR's) RISE registry, we analyzed the relationship between EHR system and performance on DA and functional status (FS) quality measures. METHODS: We analyzed data collected in 2018 from practices enrolled in RISE. We assessed practice-level performance on quality measures that require DA and FS documentation. Multivariable linear regression and zero-inflated negative binomial models were used to examine the independent effect of EHR system on practice-level quality measure performance, adjusting for practice characteristics and patient case-mix. RESULTS: In total, 220 included practices cared for 314,793 patients with RA. NextGen was the most commonly used EHR system (34.1%). We found wide variation in performance on DA and FS quality measures by EHR system (median 30.1, IQR 0-74.8, and median 9.0, IQR 0-74.2), respectively). Even after adjustment, NextGen practices performed significantly better than Allscripts on the DA measure (51.4% vs 5.0%; P<.05) and significantly better than eClinicalWorks and eMDs on the FS measure (49.3% vs 29.0% and 10.9%; P<.05). CONCLUSIONS: Performance on national RA quality measures was associated with the EHR system, even after adjusting for practice and patient characteristics. These findings suggest that future efforts to improve quality of care in RA should focus not only on provider performance reporting but also on developing and implementing rheumatology-specific standards across EHRs.

Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study.

BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31-1·57]), were male compared with female (1·38 [1·05-1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23-1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50-3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49-3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology.

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.

Epidemiology and treatment of Behçet's disease in the USA: insights from the Rheumatology Informatics System for Effectiveness (RISE) Registry with a comparison with other published cohorts from endemic regions.

BACKGROUND: Behçet's disease (BD), a chronic systemic vasculitis, has distinct geographical and ethnic variation. Data regarding the epidemiology of patients with BD in the U.S. are limited; therefore, we sought to describe BD patient characteristics and medication use in the U.S., and compared them with data from patients from endemic regions. METHODS: We conducted a cross-sectional study using data from the RISE registry (2014-2018). Patients aged ≥ 18 years with BD were included. Sociodemographic and treatment information was extracted. We compared patients from the RISE registry to data from other published studies of patients with BD from endemic areas. RESULTS: One thousand three hundred twenty-three subjects with BD from the RISE registry were included. Mean age was 48.7 ± 16.3 years, female to male ratio was 3.8:1, and 66.7% were White. The most frequently used medications included glucocorticoids (67.6%) and colchicine (55.0%). Infliximab and adalimumab were the most used biologics (14.5% and 14.1%, respectively); 3.2% of patients used apremilast. The RISE registry had more women (79.3%), and patients were older compared to previously published BD studies from endemic areas. Methotrexate and TNFi were more commonly reported in RISE (21.8% and 29.4%) compared to studies from Egypt and Turkey. Colchicine, cyclosporine, and cyclophosphamide were more commonly used in cohorts from Egypt, Turkey, and Iran. CONCLUSIONS: Findings from the largest BD dataset in the U.S. suggest that BD patients are predominantly female. Further research is needed to explore the reasons for the higher prevalence of BD among women in the U.S. and its possible impact on disease severity and management.

Factors Associated With Hospitalization and Death After COVID-19 Diagnosis Among Patients With Rheumatic Disease: An Analysis of Veterans Affairs Data.

OBJECTIVE: Individuals with autoimmune rheumatic disease (RD) are considered to be at increased risk for infection. However, few US population-based studies have assessed whether these patients are at increased risk of hospitalization or death due to COVID-19 compared with those without RD. METHODS: We performed a retrospective cohort study using national Veterans Affairs Health Care System data for individuals who tested positive for SARS-CoV-2. Outcomes of interest were hospitalization or death due to any cause within 30 days of COVID-19 diagnosis. Outcomes were compared among veterans with RD and those without RD by using propensity score matching (PSM) and mixed-effects multivariate logistic regression. RESULTS: Of 26,116 veterans with COVID-19, 501 (1.9%) had an underlying RD. Prior to matching, patients with RD were more likely to have poor outcomes compared with controls (37.7% vs. 28.5% hospitalized; 6.4% vs. 4.5% died). In the PSM analysis, RD was not a significant predictor for poor outcomes; however, patients with prescriptions for glucocorticoids had increased odds of poor outcomes in a dose-dependent manner (odds ratio [95% confidence interval] for hospitalization or death: 1.33 [1.20-1.48] for doses >0 and ≤10 mg/day; 1.29 [1.09-1.52] for doses >10 mg/day). CONCLUSION: Among US veterans with COVID-19, we did not find a significant association between RD and hospitalization or death. Poor outcomes appear to be mostly driven by age and other comorbidities, similar to the general veteran population. However, we observed an increased risk for poor outcomes among patients who received glucocorticoids, even at daily doses less than or equal to 10 mg.

Socioeconomic Disparities in Functional Status in a National Sample of Patients With Rheumatoid Arthritis.

Importance: Little is known about the association of poverty with functional status (FS) in patients with rheumatoid arthritis (RA) who use rheumatology care. Objectives: To examine the association between socioeconomic status (SES) and FS among patients with RA and to evaluate the association between SES and functional declines over time in patients who received at least some rheumatology care. Design, Setting, and Participants: This cohort study used data from the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry between January 1, 2016, and December 31, 2018. Analyses included all adult patients with a confirmed RA diagnosis (ie, had ≥2 encounters associated with RA International Classification of Diseases codes ≥30 days apart) and at least 1 FS score documented between 2016 and 2018 seen at participating rheumatology practices. Data analysis was conducted from April to December 2020. Exposures: The Area Deprivation Index (ADI), a zip code-based indicator of neighborhood poverty, was used as a proxy for SES. ADI scores were categorized into quintiles. Main Outcomes and Measures: FS measures included Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire Disability index, and Health Assessment Questionnaire-II. Cross-sectionally, mean FS scores were compared across ADI quintiles. Longitudinally, among patients with at least 2 FS scores, multilevel multivariate regression computed the probability of functional decline, defined as a change greater than the minimum clinically important difference, across ADI quintiles. In a subgroup analysis, whether disease activity mediated the association between SES and functional decline was examined. Results: Of the 83 965 patients included in the study, 66 649 (77%) were women, and 60 037 (72%) were non-Hispanic White. Mean (SD) age was 63.4 (13.7) years. MDHAQ was the most reported FS measure (56 928 patients [67.8%]). For all measures, mean (SD) FS score was worse at lower SES levels (eg, for MDHAQ quintile 1: 1.79 [1.87]; quintile 5: 2.43 [2.17]). In longitudinal analyses, the probability of functional decline was 14.1% (95% CI, 12.5%-15.7%) in the highest SES quintile and 18.9% (95% CI, 17.1%-20.7%) in the lowest SES quintile. The association between SES and functional decline was partially mediated (7%; 95% CI, 4%-22%) by disease activity. Conclusions and Relevance: In this cohort study of patients with RA, worse FS and faster declines in functioning over time were observed in patients with lower SES. These findings provide a framework for monitoring disparities in RA and for generating evidence to spur action toward achieving health equity.

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.