2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Assessing Patient Values and Preferences to Inform the 2023 American College of Rheumatology/American College of Chest Physicians Interstitial Lung Disease Guidelines.

OBJECTIVE: Patient engagement is critical to clinical practice guideline (CPG) development. This work presents our approach to ascertaining patients' values and preferences to inform the American College of Rheumatology guidelines for screening, monitoring, and treatment of interstitial lung disease (ILD) in people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We conducted a cross-sectional qualitative study of a purposefully sampled Patient Panel using a modified content analytic approach. The study team reviewed text transcripts from the Patient Panel discussion to identify themes and develop a clustered thematic schema. RESULTS: Twenty-one patients (75% women) participated, with a mean age of 53 years (range 33-73). Patients had one or more SARDs: systemic sclerosis (38%), Sjögren disease (38%), idiopathic inflammatory myopathy (33%), rheumatoid arthritis (24%), and mixed connective tissue disease (10%). We identified 10 themes in 4 thematic clusters: communication, screening and monitoring, treatment goals, and treatment adverse effects. Patients prioritized recognizing ILD symptoms, importance of ILD screening and close monitoring, goals of survival and improving quality of life, and willingness to accept treatment risks provided that there is close communication with providers. Patient representatives shared patients' priorities and insight at the Voting Panel meeting, influencing multiple guideline recommendations. CONCLUSION: Patient engagement fosters a holistic approach to CPG development, leading to recommendations aiming for the best clinical outcomes while prioritizing outcomes important for patients. The patient-identified themes played a critical role in ILD guideline development and provide core elements for shared decision-making as clinicians make management and therapeutic decisions with patients with SARD-associated ILD.

Association of Cardiovascular Outcomes with Low-Dose Glucocorticoid Use in Patients with Rheumatoid Arthritis.

OBJECTIVE: Many guidelines recommend limiting glucocorticoids in patients with rheumatoid arthritis (RA), but 40% of patients remain on glucocorticoids long-term. We evaluated the cardiovascular risk of long-term glucocorticoid use by studying patients on stable disease modifying anti-rheumatic drugs (DMARDs). METHODS: Using two claims databases, we identified patients with RA on stable DMARD therapy for >180 days. Proportional hazards models with inverse probability weights and clustering to account multiple observations were used to estimate the effect of glucocorticoid dose on composite cardiovascular outcomes (stroke or myocardial infarction). RESULTS: There were 135,583 patients in Medicare and 39,272 in Optum's de-identified Clinformatics® Data Mart (CDM) database. Medicare and CDM patients had an incidence of 1.3 and 0.8 composite cardiovascular outcomes per 100 person-years, respectively. In the older, comorbid Medicare cohort, glucocorticoids were associated with a dose-dependent increase in composite cardiovascular outcomes in adjusted models with predicted 1-year incidence of 1.4% (95% CI 1.2-1.6) for ≤5mg, 1.6% (1.4-1.9) for >5-10mg, and 1.8% (1.2-2.5) for >10mg versus 1.1% (95% CI 1.1-1.2) among patients using no glucocorticoids. There was no significant association among the CDM cohort. However, in the subgroup of younger patients with RA and higher cardiovascular risk, glucocorticoids were associated with a dose-dependent increase in composite cardiovascular outcomes. CONCLUSION: Among older, more comorbid and younger, higher cardiovascular risk patients with RA on stable DMARD therapy, glucocorticoids were associated with a dose-dependent increased risk of myocardial infarction and stroke, even at doses ≤5mg/d. By contrast, no association was noted among younger, healthier patients with RA.

Lower body mass and lower adiposity are associated with differential responses to two treatment strategies for rheumatoid arthritis.

PURPOSE: To determine if body mass index (BMI) and adipokine levels identify rheumatoid arthritis (RA) patients most likely to benefit from initiation of tumour necrosis factor inhibitors (TNFi) after methotrexate inadequate response. METHODS: This is a secondary analysis of the Rheumatoid Arthritis Comparison of Active Treatments (RACAT) trial and the (TEAR) trial. Both studies compared treatment strategies starting with conventional disease-modifying anti-rheumatic drugs (DMARDs) (triple therapy) versus etanercept plus methotrexate. We compared response rates between TNFi and triple therapy among patients with different BMI. Adipokines were measured at enrolment and associations with treatment response were examined using regression, adjusting for age, sex, BMI and baseline disease activity. RESULTS: In RACAT (n=306), participants who were normal/underweight were more likely to benefit from TNFi versus triple therapy, with greater change in Disease Activity Score in 28 and greater ACR20 response (ACR 20: 64% vs 23%, p=0.001). In contrast, overweight/obese participants had similar response to TNFi versus triple therapy (p-for-interaction=0.001). Similarly, but modest patterns were observed in TEAR (n=601; ACR20: 67% vs 52%, p=0.05). In RACAT, adipokine scores consistent with lower adiposity also predicted greater response to TNFi (ACR20: 58% vs 37%, p=0.01) with better model fit compared with BMI alone. CONCLUSIONS: Lower BMI and evidence of lower adiposity based on adipokine profiles were associated with a superior response to TNFi compared with triple therapy. There was no difference between treatments among overweight/obese participants. The results support TNFi being a particularly important therapeutic among normal/underweight patients, with implications for clinical decisions and trial design.

Using Electronic Health Records and Linked Claims Data to Assess New Medication Use and Primary Nonadherence in Rheumatology Patients.

OBJECTIVE: The objective of this study was to determine the proportion of new medication prescriptions observed in electronic health records (EHR) that represent true incident medication use, accounting for undocumented previous prescriptions (prevalent medication use) and failure to initiate treatment (primary nonadherence) with linked administrative claims data as the reference standard. METHODS: Using single-specialty rheumatology EHR data from more than 700 community practices in the United States linked to administrative claims data, we identified first (index) EHR prescriptions and assessed the positive predictive value (PPV) of different EHR-derived new user definitions to identify true incident use (no prior claims). We then assessed how often index EHR prescriptions that met a definition of new use resulted in primary nonadherence (no subsequent claims). RESULTS: Overall, 12,405 index EHR prescriptions were identified with PPVs of 0.59 to 0.67 for true incident use. PPVs increased to 0.76 to 0.85 by excluding medications listed during the EHR medication reconciliation process and further increased to 0.87 to 0.93 by requiring ≥12 elapsed months since the first rheumatology office visit. Primary nonadherence at three months was observed in 33% to 38% overall and varied substantially by medication class, ranging from 15% to 23% for conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to 54% to 64% for targeted synthetic DMARDs. CONCLUSION: New DMARD use was accurately distinguished from prevalent use with EHR prescriptions and simple new user definitions that include current medications collected during medication reconciliation. Primary nonadherence was frequent and varied by DMARD class. This has important implications for epidemiologic studies using EHR data and for optimal delivery of clinical care.

Changes in Characteristics of Patients Initiating and Discontinuing Advanced Therapies for Rheumatoid Arthritis Following the Release of Safety Data.

OBJECTIVE: The objective of this study was to determine the impact of emerging safety data on practice patterns by describing the characteristics of patients initiating and discontinuing advanced therapies for rheumatoid arthritis (RA) before and after January 2021. METHODS: This cohort study evaluated US veterans with RA between April 2019 and September 2022. This period was divided into two 664-day periods before and after January 2021. Eligible patients had ≥1 diagnosis code for RA and initiated a tumor necrosis factor inhibitor (TNFi), non-TNFi biologic, or JAK inhibitor (JAKi). We tested for interaction within regression models to determine whether changes in patient characteristics for tofacitinib recipients were different from changes observed for other therapies. We also evaluated factors associated with therapy discontinuation in Cox models adjusted for age, sex, and duration on therapy, including assessment for effect modification. RESULTS: When comparing patients with RA initiating tofacitinib before (n = 2,111) with those initiating tofacitinib after (n = 1,664) January 2021, there was a decrease in mean age (64.1 vs 63.0 years) and in the proportion with cardiovascular comorbidities (all P < 0.01). These changes were significantly different from those observed for patients initiating TNFi or non-TNFi biologics. Among active advanced therapy recipients, the likelihood of discontinuation was higher for tofacitinib than TNFi (hazard ratio 1.18, 95% confidence interval 1.10-1.26, P < 0.001). The higher rate of tofacitinib discontinuation was more pronounced in the presence of cardiovascular comorbidities (P < 0.05). CONCLUSION: Recent safety data significantly affected prescribing practices for advanced therapies, with a reduction in JAKi initiation and an increase in JAKi discontinuation among older patients and those at high cardiovascular risk.

Frailty and Risk of Serious Infections in Patients With Rheumatoid Arthritis Treated With Biologic or Targeted-Synthetic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs. METHODS: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA. Patients' baseline frailty risk score was calculated using a Claims-Based Frailty Index (≥0.2 defined as frail) 12 months prior to drug initiation. The primary outcome was time to serious infection; secondarily, we examined time-to-any infection and all-cause hospitalizations. We used Cox proportional hazards to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs) and assessed the significance of interaction terms between frailty status and drug class. RESULTS: A total of 57,980 patients, mean (±SD) age 48.1 ± 10.1 were included; 48,139 (83%) started TNFi, 8,111 (14%) non-TNFi biologics, and 1,730 (3%) JAKi. Among these, 3,560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (adjusted hazard ratio [95% CI] 1.5, 1.2-1.9) and 40% higher risk of inpatient admissions (1.4 [1.3-1.6]) compared with nonfrail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to nonfrail patients among those on TNFi (1.2 [1.1-1.3]) or non-TNFi (1.2 [1.0-1.4]) or JAKi (1.4 [1.0-2.0]). CONCLUSION: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with biologic or targeted-synthetic DMARDs.

Racial and Ethnic Distribution of Rheumatic Diseases in Health Systems of the National Patient-Centered Clinical Research Network.

OBJECTIVE: To evaluate the relative prevalence of 8 rheumatic and musculoskeletal diseases (RMDs) across racial and ethnic groups within the National Patient-Centered Clinical Research Network (PCORnet). METHODS: Electronic health records from participating PCORnet institutions and systems from January 1, 2013, to December 31, 2018, were used to identify adult patients with ≥ 2 diagnosis codes for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), osteoporosis (OP), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), giant cell arteritis (GCA), and Takayasu arteritis (TAK). Among those with race and ethnicity data available, we compared prevalence of RMDs by race and ethnicity. RESULTS: Data from 28,059,546 patients were available for analysis. RA was more common in patients who were American Indian or Alaska Native vs White, with a prevalence of 11.57 vs 10.11/1000 (odds ratio [OR] 1.15, 95% CI 1.09-1.22). SLE was more common in patients who were Black or African American (6.73/1000), American Indian or Alaska Native (3.82/1000), and Asian (3.39/1000) vs White (2.80/1000; OR 2.43, 95% CI 2.39-2.46; OR 1.39, 95% CI 1.25-1.53; OR 1.26, 95% CI 1.21-1.31, respectively). SLE was more common in patients who were Hispanic vs non-Hispanic (prevalence 3.93 vs 3.45/1000, OR 1.14, 95% CI 1.12-1.16). TAK was more common in patients who were Asian vs White (prevalence 0.05 vs 0.04/1000, OR 1.43, 95% CI 1.00-2.03). OP, RA, and the vasculitides were all more common in patients who were White vs Black or African American. CONCLUSION: These data provide important information on the prevalence of RMDs by race and ethnicity in the United States. PCORnet can be used as a reliable data source to study RMDs within a large representative population.

Changes in Patterns of Use of Advanced Therapies Following Emerging Data About Adverse Events in Patients With Rheumatoid Arthritis From the Veterans Affairs Health System.

OBJECTIVE: To determine whether prescribing practices for Janus kinase inhibitors (JAKi), tumor necrosis factor inhibitors (TNFi), and non-TNFi biologic agents changed after the results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance trial were released in January 2021. METHODS: This is a retrospective study in adult patients with rheumatoid arthritis (RA) receiving advanced therapies within the Veterans Affairs Health System from January 2012 through September 2022. Eligible patients were required to have at least one diagnosis code for RA and to have received a biologic disease-modifying antirheumatic drug or JAKi. Treatment courses were defined from pharmacy dispensing data and the number of new courses of each advanced therapy was quantified over time. We assessed changes in the use of each therapy before and after the release of safety data (January 2021). RESULTS: A total of 88,253 individual drug courses (in 34,656 unique patients) were included in the study. There was a consistent increase in the number and proportion of new courses of JAKi leading up to January 2021, which was followed by a significant net decrease in JAKi use through September 2022. There was significantly less tofacitinib use after the release of safety data, with a significant difference in the slope of change in use with time. In contrast, whereas TNFi use declined leading up to 2021, its use significantly increased after January 2021. CONCLUSION: Changes in prescribing in response to new evidence emphasize the impact that safety trials have on prescribing practices. Ongoing study in this area, with attention to specific patient characteristics and risk profiles, will help characterize these changes in practice.

Reducing Underage Drinking Through Visible Home Visits by Law Enforcement: An Efficacy Case Study Over 29 Months.

This paper describes the development and impact of an underage drinking reduction program designed and implemented by a South Carolina county sheriff's office with assistance from the county coalition. In December 2017, high school surveys identified family and friends as the alcohol source 82.2% of the time. In Summer 2018, sheriff deputies began visiting with almost all high school seniors, i.e., 1,352 high school senior visits.Deputies reminded parents to not provide alcohol to anyone under 21 years old. School surveys were conducted pre-program (December 2017), during (April 2018 and September 2018) and post-program (April 2020). Comparing the pre-effort results with post surveys found a 22.8% decline in 30-day drinking (p=.01) and a 23.5% decrease in binge drinking (p=.07). As described by Holder et al., the results provide the foundation for replication under controlled research conditions.

Patient Perceptions of Rheumatoid Arthritis Blood Work: A Cross-Sectional Survey in the ArthritisPower Registry.

OBJECTIVE: To examine how patients with rheumatoid arthritis (RA) perceive RA-related laboratory testing and the potential utility of a blood test to predict treatment response to a new RA medication. METHODS: ArthritisPower members with RA were invited to participate in a cross-sectional survey on reasons for laboratory testing plus a choice-based conjoint analysis exercise to determine how patients value different attributes of a biomarker-based test to predict treatment response. RESULTS: Most patients perceived that their doctors ordered laboratory tests to check for active inflammation (85.9%) or assess medication side effects (81.2%). The most commonly ordered blood tests used to monitor RA were complete blood counts, liver function tests, and those measuring C-reactive protein (CRP) and erythrocyte sedimentation rate. Patients felt CRP was most helpful in understanding their disease activity. Most worried their current RA medication would eventually stop working (91.4%) and they would waste time trying a new RA medication that may not work for them (81.7%). For patients who would require a future change in RA treatment, a majority (89.2%) reported that they would be very/extremely interested in a blood test that could help predict whether such new medication would be effective. Highly accurate test results (improving the chance RA medication will work from 50% to 85-95%) were more important to patients than low out-of-pocket cost (<$20) or minimal wait time (<7 days). CONCLUSIONS: Patients consider RA-related blood work important for monitoring of inflammation and medication side effects. They worry about treatment effectiveness and would undergo testing to accurately predict treatment response.

Accuracy of administrative claims prescription fill data to estimate glucocorticoid use and dose in patients with rheumatoid arthritis.

PURPOSE: To assess accuracy of administrative claims prescription fill-based estimates of glucocorticoid use and dose, and approximate bias from glucocorticoid exposure misclassification. METHODS: We identified adults with rheumatoid arthritis with linked Medicare and CorEvitas registry data. An algorithm identifying glucocorticoid use and average dose over 90 days from Medicare prescription fills was compared to physician-reported measures from a CorEvitas visit during the same period, using weighted kappa to compare doses (none, ≤5 mg, 5-10 mg, >10 mg/day). A deterministic sensitivity analysis examined the effect of exposure misclassification on estimated glucocorticoid-associated infection risk from a prior study. RESULTS: We identified 621 observations among 494 patients. Prescription fills identified glucocorticoid use in 41.9% of observations versus 31.1% identified by CorEvitas physician-report. For glucocorticoid use (yes/no), prescription fills had sensitivity 88.1% (95% CI 82.7-92.3), specificity 79.0% (74.8-82.7), PPV 65.4% (59.3-71.2), NPV 93.6% (90.6-95.9), and 81.8% agreement with CorEvitas, with kappa 0.61 (moderate to substantial agreement). There was 89.5% agreement between prescription fills and physician-reported doses, with weighted kappa 0.56 (moderate agreement). Applying these results to a prior Medicare study evaluating glucocorticoid-associated infection risk [risk ratio 1.44 (95% CI 1.41-1.48)] led to an externally adjusted risk ratio of 1.74 when accounting for exposure misclassification, representing -17% bias in infection risk estimate. CONCLUSIONS: This study supports the use of claims data to estimate glucocorticoid use and dose, but investigators should account for exposure misclassification, which may lead to underestimates of glucocorticoid risks. Our results could be applied to adjust risk estimates in other studies that use prescription fills to estimate glucocorticoid use.

Engaging Multistakeholder Perspectives to Identify Patient-Centered Research Priorities Regarding Vaccine Uptake Among Adults With Autoimmune Conditions.

OBJECTIVE: The study objective was to prioritize topics for future patient-centered research to increase uptake of common vaccines, such as for pneumococcal pneumonia, influenza, herpes zoster, human papillomavirus, and severe acute respiratory syndrome coronavirus 2, among adults living with autoimmune conditions. METHODS: A steering committee (SC) was formed that included clinicians, patients, patient advocates, and researchers associated with rheumatic diseases (psoriatic arthritis, rheumatoid arthritis, vasculitis), inflammatory bowel disease, and multiple sclerosis. Through a scoping review and discussions, SC members identified research topics regarding vaccine uptake and/or hesitancy for prioritization. A larger multistakeholder alliance that included patients and patient advocates, clinicians, researchers, policy makers, regulators, and vaccine manufacturers conducted a modified Delphi exercise online with three rating rounds and one ranking round. Frequency analysis and comparisons across stakeholder groups were conducted. A weighted ranking score was generated for each item in the ranking round for final prioritization. RESULTS: Through the Delphi process, 33 research topics were identified, of which 13 topics were rated as critical by more than 70% of all stakeholders (n = 31). The two highest ranked critical topics per the full stakeholder group were "How well a vaccine works for adults with autoimmune conditions" and "How beliefs about vaccine safety affect vaccine uptake." CONCLUSION: A multistakeholder group identified key topics as critically important priorities for future research to decrease vaccine hesitancy and improve uptake of vaccines for adults with autoimmune conditions.

Circulating Adipokines and Associations With Incident Cardiovascular Disease in Rheumatoid Arthritis.

OBJECTIVE: To assess whether circulating levels of adiponectin, leptin, and fibroblast growth factor 21 (FGF-21) are associated with incident cardiovascular disease (CVD) in rheumatoid arthritis (RA). METHODS: Adipokines were measured using banked enrollment serum from patients with RA and dichotomized above/below the median value. Incident CVD events (coronary artery disease [CAD], stroke, heart failure [HF] hospitalization, venous thromboembolism, CVD-related deaths) were identified using administrative data and the National Death Index. Covariates were derived from medical record, biorepository, and registry databases. Multivariable Cox models were generated to quantify associations between adipokine concentrations and CVD incidence. Five-year incidence rates were predicted. RESULTS: Among 2,598 participants, 639 (25%) had at least 1 CVD event over 19,585 patient-years of follow-up. High adiponectin levels were independently associated with HF hospitalization (hazard ratio [HR] 1.39 [95% confidence interval (95% CI) 1.07-1.79], P = 0.01) and CVD-related death (HR 1.49 [95% CI 1.16-1.92], P = 0.002) but not with other CVD events. High leptin was independently associated with CVD-related death (HR 1.44 [95% CI 1.05-1.97], P = 0.02). High FGF-21 levels were independently associated with lower rates of CAD (HR 0.75 [95% CI 0.58-0.97], P = 0.03). In subgroup analyses, associations between high adiponectin and leptin levels with CVD-related death were driven by strong associations in nonobese patients. CONCLUSION: Adipokines are associated with HF hospitalization and CVD-related death in patients with RA, with stronger associations in nonobese participants. These findings suggest that adipokines effectively predict clinically important outcomes in RA perhaps through an association with body composition and metabolic health. Further study is needed to determine whether adipokine measures might augment existing tools to identify RA patients at increased risk of CVD.

Adipocytokines and Associations With Abnormal Body Composition in Rheumatoid Arthritis.

OBJECTIVE: We determined associations between adipokines and abnormal body composition in patients with rheumatoid arthritis (RA). METHODS: Combining data from three RA cohorts, whole-body dual-energy absorptiometry measures of appendicular lean mass and fat mass indices were converted to age-, sex-, and race- and ethnicity-specific Z scores. Lean mass relative to fat mass was determined based on prior methods. Independent associations between body composition profiles and circulating levels of adiponectin, leptin, and fibroblast growth factor (FGF)-21 were assessed using linear and logistic regression models adjusting for demographic characteristics and study cohort. We also determined the improvement in the area under the curve (AUC) for prediction of low lean mass when adipokines were added to predictive models that included clinical factors such as demographic characteristics, study, and body mass index (BMI). RESULTS: Among 419 participants, older age was associated with higher levels of all adipokines, whereas higher C-reactive protein level was associated with lower adiponectin levels and higher FGF-21 levels. Greater fat mass was strongly associated with lower adiponectin levels and higher leptin and FGF-21 levels. Higher levels of adiponectin, leptin, and FGF-21 were independently associated with low lean mass. The addition of adiponectin and leptin levels to regression models improved prediction of low lean mass when combined with demographic characteristics, study, and BMI (AUC 0.75 vs. 0.66). CONCLUSION: Adipokines are associated with both excess adiposity and low lean mass in patients with RA. Improvements in the prediction of body composition abnormalities suggest that laboratory screening could help identify patients with altered body composition who may be at greater risk of adverse outcomes.

Rheumatoid Arthritis Disease Activity and Hospitalized Infection in a Large US Registry.

OBJECTIVES: The association between disease activity and infection risk among patients with rheumatoid arthritis (RA) is not clear, and it is challenging to determine because of confounding due to the effects of RA treatments and comorbidities. METHODS: Using patients with RA in the CorEvitas registry with Medicare coverage in 2006-2019, we identified eligible patients who had at least 1 visit with moderate disease activity based on the Clinical Disease Activity Index (CDAI; CDAI >10 and ≤22). Follow-up started at the subsequent CorEvitas visit. Hospitalized infection during follow-up was assessed in linked Medicare data. We calculated the incidence rate of hospitalized infection for patients in remission, and low and moderate disease activity, and estimated the effect of time-varying CDAI on hospitalized infection by controlling for baseline and time-dependent confounders using marginal structural models (MSMs). RESULTS: A total of 3,254 patients with RA were eligible for analysis, among which 529 hospitalized infections were identified during follow-up. The crude incidence of hospitalized infection was 3.8 per 100 person-years for patients in remission, 6.6 for low disease activity, and 8.0 for moderate disease activity. Using MSMs and compared with being in remission, the hazard ratio of hospitalized infection associated with low disease activity was 1.60 (95% confidence interval [95% CI] 1.13-2.28) and with moderate disease activity was 1.83 (95% CI 1.30-2.64). CONCLUSION: The risk of hospitalized infection was higher for patients with RA in low or moderate disease activity than for those in remission after accounting for the interplay of disease activity, RA treatments, treatment switching, and other potential confounders.

Associations Between Low Serum Urate, Body Composition, and Mortality.

OBJECTIVE: Controversy remains as to whether low serum urate or uric acid (UA) levels contribute to adverse outcomes. We evaluated the relation between low serum UA levels and sarcopenia and assessed whether sarcopenia confounds associations between these low levels and mortality. METHODS: We utilized data from the National Health and Nutrition Examination Survey (1999-2006). Participants with available whole-body dual x-ray absorptiometry body composition measurements and serum UA concentrations were included. Body composition assessments included body mass index (BMI), waist circumference, maximum lifetime BMI, and age-, sex-, and race-specific appendicular lean mass index (ALMI) and fat mass index (FMI) Z scores. We also calculated Z scores for ALMI relative to FMI (ALMIFMI ). We evaluated associations between serum UA levels and body composition using logistic regression and assessed associations between serum UA levels and mortality before and after adjusting for differences in body composition using Cox proportional hazards regression. RESULTS: Among the 13,979 participants, low serum UA concentrations (<2.5 mg/dl in women, <3.5 mg/dl in men) were associated with low lean mass (ALMI and ALMIFMI Z scores), underweight BMI (<18.5 kg/m2 ), and higher rates of weight loss. The proportion of patients with low ALMI Z scores was 29% in the low serum UA group and 16% in the normal serum UA group (P = 0.001). Low serum UA levels were associated with increased mortality before we adjusted for body composition (hazard ratio 1.61 [95% confidence interval 1.14-2.28]; P = 0.008) but was attenuated and not significant after adjustment for body composition and weight loss (hazard ratio 1.30 [95% confidence interval 0.92-1.85], P = 0.13). CONCLUSION: Sarcopenia and weight loss are more common among patients with low serum UA concentrations. Differences in body composition may help to explain associations between low levels of serum UA and higher mortality.