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Patients with rheumatoid arthritis (RA) have an increased risk of select cancers, including lymphoma and lung cancer. Whether RA influences prostate cancer risk is uncertain. We aimed to determine the risk of prostate cancer in patients with RA compared to patients without RA in the Veterans Health Administration (VA).We performed a matched (up to 1:5) cohort study of male patients with and without RA in the VA from 2000 to 2018. RA status, as well as covariates, were obtained from national VA databases. Prostate cancer was identified through linked VA cancer databases and the National Death Index. Multivariable Cox models compared prostate cancer risk between patients with RA and patients without RA, including models that accounted for retention in the VA system.We included 56,514 veterans with RA and 227,284 veterans without RA. During 2,337,104 patient-years of follow-up, 6,550 prostate cancers occurred. Prostate cancer incidence (per 1,000 patient-years) was 3.50 (95% confidence interval [95% CI] 3.32-3.69) in patients with RA and 2.66 (95% CI 2.58-2.73) in patients without RA. After accounting for confounders and censoring for attrition of VA health care, RA was modestly associated with a higher prostate cancer risk (adjusted HR [HRRA was associated with a modestly increased risk of prostate cancer, but not prostate cancer mortality, after accounting for relevant confounders and several potential sources of bias. However, even minimal unmeasured confounding could explain these findings.

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).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.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.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.

Rheumatoid arthritis (RA) involves chronic inflammation of synovial joints, causing pain, stiffness, and limited mobility. 18F-sodium fluoride (NaF) is a PET tracer whose uptake reflects bone turnover, while 18F-fludeoxyglucose (FDG) shows glucose metabolism and can serve as a marker for inflammation. The aim of this study is to determine the feasibility of calculating the FDG and NaF mean standardized uptake value (SUVmean) in the knee joint, hip joint, and sacroiliac (SI) joint of RA patients and to determine their association with patient characteristics. Prospective FDG-PET/CT as well as NaF-PET/CT imaging was performed on 18 RA patients. The global SUVmean was calculated on FDG-PET/CT and NaF-PET/CT images using a semiautomated CT-based method of segmentation. FDG and NaF uptake were found to be significantly correlated in the knee (r = 0.77, p < 0.001), but not in the hip and SI joints. In the knee, both NaF SUVmean and FDG SUVmean were significantly correlated with body weight, BMI, leptin, and sclerostin levels (p < 0.05). NaF SUVmean was significantly positively correlated with BMI and leptin for both the hip and SI joints (p < 0.05). No significant correlation was observed between either PET parameter and age, height, erythrocyte sedimentation rate (ESR), and interleukins 1 and 6 (IL-1 and IL-6); however, FDG was correlated with inflammatory markers such as C-reactive protein (CRP) and patient global visual analogue scale (VAS-PtGlobal) in some joints. In this study, both FDG and NaF uptake were quantified in large joints of patients with RA using CT segmentation. NaF and FDG SUVmean were correlated with clinical variables related to body weight and adiposity, suggesting that degenerative joint disease may play a larger role in influencing the uptake of these tracers in large joints than RA disease activity. FDG and its correlation with markers of inflammation such as CRP and VAS-PtGlobal suggests that this tracer may serve as a more specific marker for RA disease activity than NaF. Larger prospective and longitudinal data are necessary to gain a better understanding of the roles of FDG and NaF in evaluating RA joint activity in these joints.

Objectives To determine whether RA and interstitial lung disease (ILD) severity measures are associated with survival in patients with RA-ILD. Methods We studied US veterans with RA-ILD participating in a multicentre, prospective RA cohort study. RA disease activity (28-joint DAS [DAS28-ESR]) and functional status (multidimensional HAQ [MDHAQ]) were collected longitudinally while pulmonary function tests (forced vital capacity [FVC], diffusing capacity for carbon monoxide) were obtained from medical records. Vital status and cause of death were determined from the National Death Index and administrative data. Predictors of death were assessed using multivariable Cox regression models adjusting for age, sex, smoking status, ILD duration, comorbidity burden and medications. Results We followed 227 RA-ILD participants (93% male and mean age of 69 years) over 1073 person-years. Median survival after RA-ILD diagnosis was 8.5 years. Respiratory diseases (28%) were the leading cause of death, with ILD accounting for 58% of respiratory deaths. Time-varying DAS28-ESR (adjusted hazard ratio [aHR] 1.21; 95% CI: 1.03, 1.41) and MDHAQ (aHR 1.85; 95% CI: 1.29, 2.65) were separately associated with mortality independent of FVC and other confounders. Modelled together, the presence of either uncontrolled disease activity (moderate/high DAS28-ESR) or FVC impairment ( Conclusion Both RA and ILD disease severity measures are independent predictors of survival in RA-ILD. These findings demonstrate the prognostic value of monitoring the systemic features of RA-ILD.

Objectives This study assessed whether circulating levels of adiponectin and leptin are associated with higher mortality in patients with RA. Methods Participants were adults from the Veterans Affairs RA Registry. Adipokines and inflammatory cytokines were measured as part of a multi-analyte panel on banked serum at enrolment. Dates and causes of death were derived from the Corporate Data Warehouse and the National Death Index. Covariates were derived from medical record, biorepository and registry databases. Multivariable Cox proportional hazard models evaluated associations between biomarkers and all-cause and cause-specific mortality. Results A total of 2583 participants were included. Higher adiponectin levels were associated with older age, male sex, white race, lower BMI, autoantibody seropositivity, radiographic damage, longer disease duration, prednisone use and osteoporosis. Higher adiponectin concentrations were also associated with higher levels of inflammatory cytokines but not higher disease activity at enrolment. Leptin was primarily associated with greater BMI and comorbidity. The highest quartile of adiponectin (vs lowest quartile) was associated with higher all-cause mortality [hazard ratio (HR): 1.46 (95% CI: 1.11, 1.93), P = 0.009] and higher cardiovascular mortality [HR: 1.85 (95% CI: 1.24, 2.75), P = 0.003], after accounting for covariates. Higher leptin levels were also associated with greater all-cause and cancer mortality. Conclusions Elevations in adipokines are associated with age, BMI, comorbidity and severe disease features in RA and independently predict early death. Associations between adiponectin and inflammatory cytokines support the hypothesis that chronic subclinical inflammation promotes metabolic changes that drive elevations in adipokines and yield adverse health outcomes.

PURPOSE Fluctuations in weight have been linked to cardiovascular (CV) outcomes in the general population. We evaluated whether weight fluctuation was independently predictive of CV events in patients with rheumatoid arthritis (RA). METHODS We studied patients with RA from the Corrona registry. Weight change was categorized as loss of ≥10%, loss of 5-10%, stable, gain of 5-10%, and gain of ≥10%. We also categorized patients by quintile of variability in weight in prior observation periods. Cox proportional hazard models explored independent associations between time-varying weight change and weight variability and risk of CV events before and after adjusting for CV risk factors, RA disease features, and disability. RESULTS Among 31,381 participants, those that lost or gained 10% of their weight had greater disease activity, worse physical function, and were more likely to smoke, have diabetes, use corticosteroids, and be disabled. In adjusted models, a greater risk of CV events was observed in those that experienced 10% weight loss [HR: 1.18 (1.03,1.36) p=0.02] or weight gain [HR 1.20 (1.04,1.38) p=0.01]. The association between weight change and CV events was stronger among participants with BMI

To examine temporal trends in all-cause and cause-specific mortality in patients with rheumatoid arthritis (RA) in the Veteran's Health Administration (VHA).We conducted a matched cohort study in the VHA from 1/1/2000-12/31/2017. Incident RA patients were matched up to 1:10 on age, sex, and VHA enrollment year to non-RA patients, then followed until death or end of study period. Cause of death was obtained from the National Death Index. Multivariable Cox regression models stratified by RA diagnosis years were used to examine trends in RA-related risk of all-cause and cause-specific mortality.Among 29,779 incident RA patients (matched to 245,226 non-RA patients), 9,565 deaths occurred. RA patients were at increased risk of all-cause (aHR 1.23, 95% CI 1.20-1.26), cardiovascular (aHR 1.19, 1.14-1.23), cancer (aHR 1.19, 1.14-1.24), respiratory (aHR 1.46, 1.38-1.55), and infection-related mortality (aHR 1.59, 1.41-1.80). Interstitial lung disease (ILD) was the cause of death most strongly associated with RA (aHR 3.39, 2.88-3.99). Nearly 70% of excess deaths in RA were attributable to cardiopulmonary disease. All-cause mortality risk related to RA was lower among those diagnosed during 2012-2017 (aHR 1.10, 1.05-1.15) compared to 2000-2005 (aHR 1.31, 1.26-1.36), but still higher than non-RA controls (p0.001). Cause-specific mortality trends were similar.Excess RA-related mortality was driven by cardiovascular, cancer, respiratory, and infectious causes, particularly cardiopulmonary diseases. Though our findings support that RA-related mortality risk is decreasing over time, a mortality gap remains for all-cause and cause-specific mortality in RA. This article is protected by copyright. All rights reserved.

BackgroundUrate-lowering therapy (ULT) adherence is low in gout, and few, if any, effective, low-cost, interventions are available. Our objective was to assess if a culturally appropriate gout-storytelling intervention is superior to an attention control for improving gout outcomes in African-Americans (AAs).MethodsIn a 1-year, multicenter, randomized controlled trial, AA veterans with gout were randomized to gout-storytelling intervention vs. a stress reduction video (attention control group; 1:1 ratio). The primary outcome was ULT adherence measured with MEMSCap™, an electronic monitoring system that objectively measured ULT medication adherence.ResultsThe 306 male AA veterans with gout who met the eligibility criteria were randomized to the gout-storytelling intervention (n= 152) or stress reduction video (n= 154); 261/306 (85%) completed the 1-year study. The mean age was 64 years, body mass index was 33 kg/m2, and gout disease duration was 3 years. ULT adherence was similar in the intervention vs. control groups: 3 months, 73% versus 70%; 6 months, 69% versus 69%; 9 months, 66% versus 67%; and 12 months, 61% versus 64% (p> 0.05 each). Secondary outcomes (gout flares, serum urate and gout-specific health-related quality of life [HRQOL]) in the intervention versus control groups were similar at all time points except intervention group outcomes were better for the following: (1) number of gout flares at 9 months were fewer, 0.7 versus 1.3 in the previous month (p= 0.03); (2) lower/better scores on two gout specific HRQOL subscales: gout medication side effects at 3 months, 32.8 vs. 39.6 (p= 0.02); and unmet gout treatment need at 3 months, 30.9 vs. 38.2 (p= 0.003), and 6 months, 29.5 vs. 34.5 (p= 0.03), respectively.ConclusionsA culturally appropriate gout-storytelling intervention was not superior to attention control for improving gout outcomes in AAs with gout.Trial registrationRegistered atClinicalTrials.govNCT02741700

Rheumatoid arthritis (RA) and its treatments are associated with an increased risk of infection, but it remains unclear whether these factors have an impact on the risk or severity of COVID-19. The present study was undertaken to assess the risk and severity of COVID-19 in a US Department of Veterans Affairs (VA) cohort of patients with RA and those without RA.A matched cohort study using national VA data was conducted. Patients diagnosed as having RA were identified among nondeceased individuals who were active in the VA health care system as of January 1, 2020 and who had received care in a VA medical center in 2019; patients for whom no RA diagnostic code was indicated were matched to the RA patients (1:1) by age, sex, and VA site (non-RA controls). Patients diagnosed as having COVID-19 and those with severe COVID-19 (defined as requiring hospitalization or leading to death) were ascertained from a national VA COVID-19 surveillance database through December 10, 2020. Multivariable Cox models were used to compare the risk of COVID-19 and COVID-19 hospitalization or death between RA patients and non-RA controls, after adjusting for demographic characteristics, comorbidities, health care utilization and access, and county-level COVID-19 incidence rates.This VA cohort of RA patients and non-RA controls (n = 33,886 subjects per group) predominantly comprised male patients (84.5%), and the mean age was 67.8 years. During follow-up, 1,503 patients in the cohort were diagnosed as having COVID-19; among them, 388 patients had severe COVID-19 (hospitalization or death), while in 228 patients, the deaths were not related to COVID-19. In the multivariable model, RA was associated with a higher risk of COVID-19 (adjusted hazard ratio [HR] 1.25 [95% confidence interval (95% CI) 1.13-1.39]) and a higher risk of COVID-19 hospitalization or death (adjusted HR 1.35 [95% CI 1.10-1.66]) as compared to non-RA controls. Use of disease-modifying antirheumatic drugs and prednisone, as well as self-reported Black race, self-reported Hispanic ethnicity, and presence of several chronic conditions, but not seropositivity for RA autoantibodies, were each associated with risk of COVID-19 and severe COVID-19 (hospitalization or death).Patients with RA are at higher risk of developing COVID-19 and severe COVID-19 (leading to hospitalization or death) compared to those without RA. With a risk of COVID-19 that approaches that of other recognized chronic conditions, these findings suggest that RA patients should be prioritized for COVID-19 prevention and management strategies.

OBJECTIVE Glucocorticoids are recommended for short-term use in rheumatoid arthritis (RA), but many patients continue receiving long-term therapy. We evaluated the variability in glucocorticoid prescribing across rheumatologists to inform interventions to limit long-term glucocorticoid use to the lowest dose necessary. METHODS Two cohorts were created using Medicare data from 2006 to 2015. Using cohort 1 (RA patients receiving disease-modifying antirheumatic drugs [DMARDs]), we calculated each rheumatologist's "provider preference" for glucocorticoids (frequency of use compared to other providers), using the ratio of observed to expected number of patients receiving glucocorticoids to account for case mix. In cohort 2 (RA patients receiving stable DMARD therapy), we evaluated whether provider preference for glucocorticoids could independently predict use of ≥5 mg/day of glucocorticoids 6-9 months after initiation of DMARD therapy. RESULTS Using cohort 1 (1,272,644 yearly observations; 385,597 patients), we calculated provider preference among 6,875 rheumatologists (28,936 yearly observations). Provider preference was highly variable, with physicians at the lowest and upper quartiles prescribing glucocorticoids 33% less often to 31% more often (25th and 75th percentiles, respectively) than expected. In cohort 2 (155,539 patients receiving stable DMARD therapy), provider preference was strongly associated with glucocorticoid use ≥5 mg/day at 6-9 months, with a predicted probability of use of 22% (95% confidence interval [95% CI] 21.7-22.7) versus 11% (95% CI 10.2-10.9) for a patient seeing a provider in the highest versus lowest quintile of preference. CONCLUSION Glucocorticoid prescribing for RA varies greatly among rheumatologists, and provider preference is one of the strongest predictors of a patient's long-term glucocorticoid use. These findings raise quality of care concerns and highlight the need for stronger evidence to guide RA treatment.

Objective We determined the prevalence of sarcopenic obesity in patients with RA using multiple methods and assessed associations with physical functioning. Methods This study evaluated data from three RA cohorts. Whole-body dual-energy absorptiometry (DXA) measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI) were converted to age, sex and race-specific Z-Scores and categorized using a recently validated method and compared it to a widely-used existing method. The prevalence of body composition abnormalities in RA was compared with two reference populations. In the RA cohorts, associations between body composition and change in the HAQ and the Short Physical Performance Battery (SPPB) in follow-up were assessed using linear and logistic regression, adjusting for age, sex, race and study. Results The prevalence of low lean mass and sarcopenic obesity was higher in patients with RA (14.2; 12.6%, respectively) compared with the reference population cohorts (7–10%; 4–4.5%, respectively, all P Conclusion RA patients had higher rates of low lean mass and sarcopenic obesity than the general population. The recently validated methods characterized body composition changes differently from traditional methods and were more strongly associated with physical function.

Although there is a substantial body of literature focused on understanding noninhalational risk-factors for rheumatoid arthritis, the data are mixed and often conflicting. Given the other health benefits for certain lifestyle modifications, it seems reasonable for clinicians to promote healthy lifestyle habits related to diet, exercise, maintenance of health weight, and maintenance of good dental hygiene. Overall, however, these lifestyle modifications may be expected to have modest benefit, and other strategies to prevent rheumatoid arthritis in high-risk patients are needed.

Sarcopenia is a condition characterized by decreased muscle strength and muscle mass, which can impact physical function. Sarcopenia develops as a consequence of age-related decline (primary sarcopenia) and has a major impact on physical, social, and emotional well-being. In addition, patients with rheumatic diseases may suffer from sarcopenia independently of aging (secondary sarcopenia). Exercise, pharmacological treatments, and nutritional supplementation are some of the strategies used for the management of sarcopenia in the general population. The aim of this review is to summarize the evidence around the prevalence and impact of sarcopenia in patients with rheumatic diseases.From our review, we can state that sarcopenia is a common and prevalent condition among the rheumatic diseases. Furthermore, the impacts of sarcopenia are not well-appreciated, and the implementation of treatment strategies has not been widespread. Strategies such as exercise and some pharmacological treatments are effective in improving physical and functional impairment related to these conditions.New pharmacological treatments are being actively studied and may contribute in the future to the management of sarcopenia.

People with rheumatoid arthritis (RA) have both disease-specific risk factors for osteoporosis and fractures in addition to those that affect the general population. Disease specific risks include directly pathogenic auto-antibodies, chronic exposure to systemic inflammation, and joint damage causing early disability. Risk factors that affect the general population which may have a higher prevalence in RA include smoking, calcium and vitamin D deficiency as well as hypogonadism. Additionally, chronic exposure to glucocorticoids results in reduced bone mineral density and body composition changes which can further increase fracture risk. In this review we discuss these risk-factors for osteoporosis as well as factors that may impact fall and fracture risk in people with RA.

OBJECTIVE The present study was undertaken to evaluate whether the rate of incident chronic opioid use is higher in obese patients with rheumatoid arthritis (RA). METHODS Participants with RA in the FORWARD databank were asked about their use of weak and strong opioid medications on semiannual surveys. Incident chronic opioid use was defined as new reported use extending over 2 contiguous surveys (~7-12 months). Cox proportional hazards models were used to evaluate associations between body mass index (BMI) at enrollment and incident chronic opioid use (overall use and strong opioid use). Models adjusted for demographics, smoking, disease duration, RA treatments, household income, and education level. The predicted 5-year cumulative incidence was calculated from Cox models. RESULTS Among 19,794 participants, 2,802 experienced an incident episode of chronic opioid use over 93,254 person-years of follow-up. Higher BMI was associated with higher risk of chronic opioid use. Severe obesity (BMI >35 kg/m2 ) was associated with a higher risk of overall use (adjusted hazard ratio [HRadj ] 1.74 [95% confidence interval (95% CI) 1.72-2.04], P < 0.0001) and strong opioid use (HRadj 2.11 [95% CI 1.64-2.71], P < 0.001) compared to normal BMI. This association was partially explained by greater comorbidity, pain, and disability in obese groups. The attributable risk for obesity was 15% of overall opioid use and 24% of strong opioid use. CONCLUSION Obesity is associated with a substantially higher risk of incident chronic opioid use. Approximately 1 in 4 cases of incident use of strong opioids may be attributable to obesity, suggesting a major public health impact. Interventions to prevent or reduce obesity could have an important impact on the use of opioids.

OBJECTIVE To define the minimum clinically important improvement (MCII) and minimum clinically important worsening (MCIW) for the Patient Activity Scale II (PAS-II; range 0-10), a recommended patient-reported outcome measuring rheumatoid arthritis disease activity. METHODS Data were taken from Forward, The National Databank for Rheumatic Diseases, from four 6-month data collection periods. Both anchor-based and distribution-based methods were used to estimate the MCII and MCIW. Anchor-based analyses used comparisons of pain and general health to the previous 6 months. Distribution-based analyses used 0.5 and 0.35 SDs. We stratified analyses based on the PAS-II score (above/below 3.7), hypothesizing that the MCII and MCIW would depend on the baseline score. To assess construct validity, we evaluated the odds of achieving the MCII in patients receiving new therapies. RESULTS In the overall sample, for pain and general health anchor questions, the MCIW was 0.50 and 0.55, respectively. The MCII was defined as 0.39 and 0.45, respectively, for pain and general health. The MCIW for anchor-based methods among participants with low disease activity was 1.10 (1.09/1.11 [pain/general health]), while the MCII for those with moderate-to-high disease activity was 1.09 (1.15/1.02 [pain/general health]). Distribution-based methods for 0.5 and 0.35 SD were 1.08 and 0.76, respectively, for pain and general health. There was fair-to-excellent agreement with clinically important differences in assessments of pain and disability. Patients receiving new treatments had 30% greater odds of achieving the MCII. CONCLUSION The minimum important change in PAS-II score was approximately 0.5. Among participants with a moderate-to-high PAS-II score , the MCII was 1.1, and among participants with low disease activity, the MCIW was 1.1.

Biosimilar therapies and their naming conventions are both relatively new to the drug development market and in clinical practice. We studied the use of the four-letter naming convention in practice and the knowledge, perceptions, and preferences of US health care providers. A survey was distributed among health care professionals with a history of utilizing biosimilars in clinical practice to measure key knowledge and the presence of discernable naming trends. Differences in responses across pre-hypothesized subgroups were tested for statistical significance. Of the 506 surveys emailed, 83 (16%) people responded. Overall, there was poor knowledge about the key concepts surrounding biosimilars. For example, only 52% of respondents correctly identified that biosimilars were not the same as the generic drug; however, frequent use correlated with superior knowledge across all groups. In reference to naming preferences, 67% of all respondents indicated that they commonly use the brand name to distinguish biosimilars in clinical practice and a majority of them (85%) indicated that the brand name was easier to remember than the nonproprietary name with the four-letter suffix. An unexpected number of neutral responses was documented. Notably, more than half of respondents (68%) indicated a neutral response when asked if the four-letter suffix promoted medical errors. There remains a knowledge gap with regard to biosimilars, and lack of consensus on how the naming convention is and should be utilized in clinical practice. The data also suggest that effective biosimilar education could aid in promoting familiarity with the naming convention among health care providers.

MUC5B and TOLLIP single nucleotide polymorphisms (SNPs) and cigarette smoking were associated with rheumatoid arthritis-interstitial lung disease (RA-ILD) in a predominantly Northern European population. We evaluated whether RA-ILD is associated with these genetic variants and HLA-DRB1 shared epitope (SE) alleles in a large RA cohort stratified by race and smoking history.HLA-DRB1 SE alleles and MUC5B rs35705950 and TOLLIP rs5743890 SNPs were genotyped in U.S. veterans with RA. ILD was validated through medical record review. Genetic associations with ILD were assessed in logistic regression models overall and in subgroups defined by race and smoking status, with additive interactions assessed by the relative excess risk of interaction (RERI).Of 2,556 participants (88% male, 77% White), 238 (9.3%) had ILD. The MUC5B variant was associated with ILD (OR 2.25 [95% CI 1.69, 3.02]), whereas TOLLIP and HLA-DRB1 SE were not. The MUC5B variant was less frequent among Black/African American participants (5.8% vs. 22.6%), though its association with RA-ILD was numerically stronger (OR 4.23 [1.65, 10.86]) compared to all other participants (OR 2.32 [1.70, 3.16]). Those with the MUC5B variant and a smoking history had numerically higher odds of ILD (OR 4.18 [2.53, 6.93]) than non-smokers (OR 2.41 [1.16, 5.04]). Additive interactions between MUC5B-race and MUC5B-smoking were not statistically significant.In this large RA cohort, the MUC5B promoter variant was associated with2-fold higher odds of RA-ILD. While this variant is less common among Black/African American patients, its presence in this population carried4-fold higher odds of RA-ILD.

In this chapter, we emphasize among rheumatoid arthritis (RA) patients, whom and how to screen for osteoporosis. We highlight certain modalities, advancements in technology, secondary osteoporosis workup, and laboratory testing as well as their caveats. Finally, we discuss current guidance on how to direct the laboratory and radiology testing in the context of the individual patient with RA to guide and select from the osteoporosis treatment options currently available.

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.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 (ALMIAmong 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 ALMISarcopenia 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.

BACKGROUND: We aimed to compare concerns, social distancing, health care disruptions, and telemedicine use in patients with autoimmune rheumatic disease (ARD) and non-ARD and to evaluate factors associated with immunomodulatory medication interruptions. METHODS: Patients in a multistate community rheumatology practice network completed surveys from April 2020 to May 2020. Adults with common ARD (rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus) or non-ARD (gout, osteoarthritis, osteoporosis) were evaluated. Concerns about coronavirus disease 2019 (COVID-19), social distancing, health care disruptions, and telemedicine use were compared in patients with ARD versus non-ARD, adjusting for demographics, rural residence, and zipcode-based measures of socioeconomic status and COVID-19 activity. Factors associated with medication interruptions were assessed in patients with ARD. RESULTS: Surveys were completed by 2319/36 193 (6.4%) patients with non-ARD and 6885/64 303 (10.7%) with ARD. Concerns about COVID-19 and social distancing behaviors were similar in both groups, although patients receiving a biologic or Janus kinase (JAK) inhibitor reported greater concerns and were more likely to avoid friends/family, stores, or leaving the house. Patients with ARD were less likely to avoid office visits (45.2% vs. 51.0%, odds ratio [OR] 0.79 [0.70-0.89]) with similar telemedicine use. Immunomodulatory medications were stopped in 9.7% of patients with ARD, usually (86.9%) without a physician recommendation. Compared with patients with an office visit, the likelihood of stopping medication was higher for patients with a telemedicine visit (OR 1.54 [1.19-1.99]) but highest for patients with no visits (OR 2.26 [1.79-2.86]). CONCLUSION: Patients with ARD and non-ARD reported similar concerns about COVID-19 and similar social distancing behaviors. Missed office visits were strongly associated with interruptions in immunomodulatory medication.

OBJECTIVE Rheumatoid arthritis (RA) is associated with low muscle density due to the accumulation of intramuscular fat. The present study was undertaken to identify predictors of changes in muscle density and to determine whether low muscle density predicted changes in strength and physical function. METHODS Patients with RA, ages 18-70 years, completed whole-body dual-energy x-ray absorptiometry and peripheral quantitative computed tomography to quantify lean and fat mass indices and muscle density. Dynamometry was used to measure strength at the hand, knee, and lower leg. Disability and physical function were measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). Assessments were performed at baseline and at follow-up. Regression analyses assessed associations between patient characteristics, muscle density, and deteriorations in strength and function. RESULTS Muscle density was assessed at baseline in 107 patients with RA. Seventy-nine of these patients (74%) returned for a follow-up assessment at a median follow-up time of 2.71 years (interquartile range 2.35-3.57). Factors associated with declines in muscle density included female sex, higher disease activity, smoking, and lower insulin-like growth factor 1 (IGF-1) levels. Greater muscle density Z score at baseline (per 1 SD) was associated with less worsening per year according to HAQ, SPPB, and 4-meter walk time scores and a lower risk of a clinically important worsening in HAQ score (odds ratio [OR] 1.90 [95% confidence interval (95% CI) 1.06, 3.42]; P = 0.03) and walking speed (OR 2.87 [95% CI 1.05, 7.89]; P = 0.04). CONCLUSION Worsening of skeletal muscle density occurred in patients with higher disease activity, in smokers, and in those with lower IGF-1. Low muscle density was associated with worsening of physical function. Interventions addressing reductions in muscle quality might prevent functional decline.

OBJECTIVE. To determine the association of inhalant exposures with rheumatoid arthritis (RA)–related autoantibodies and severity in US veterans. METHODS. Participants in the Veterans Affairs Rheumatoid Arthritis (VARA) registry were mailed surveys assessing occupational, agricultural, and military inhalant exposures. Demographic characteristics, disease activity, functional status, and extraarticular features were obtained from the VARA registry, while HLA–DRB1 shared epitope (SE) status, anti–cyclic citrullinated peptide (anti-CCP) antibodies, and rheumatoid factor (RF) were measured using banked DNA/serum from enrollment. Associations between inhalant exposures and RA-related factors (autoantibodies, severity, and extraarticular features) were assessed using multivariable linear and logistic regression models adjusted for age, sex, race, and tobacco use and stratified by SE status. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS. Questionnaires were returned by 797 of 1,566 participants (50.9%). Survey respondents were older, more often White or male, and less frequently smokers, and had lower disease activity compared to nonrespondents. Anti-CCP positivity was more common among veterans exposed to burn pits (OR 1.66 [95% CI 1.02, 2.69]) and military waste disposal (OR 1.74 [95% CI 1.04, 2.93]) independent of other factors. Among participants who were positive for SE alleles, burn pit exposure (OR 5.69 [95% CI 2.73, 11.87]) and military waste disposal exposure (OR 5.05 [95% CI 2.42, 10.54]) were numerically more strongly associated with anti-CCP positivity. Several inhalant exposures were associated with the presence of chronic lung disease, but not with the presence of RF or the level of disease activity. CONCLUSION. Military burn pit exposure and military waste disposal exposure were independently associated with the presence of anti-CCP antibodies in RA patients. These findings are consistent with emerging evidence that various inhalant exposures influence autoantibody expression and RA risk.

PurposeRheumatoid arthritis (RA) is associated with a higher risk of diabetes mellitus (DM). Our aim was to determine associations between inflammatory disease activity (including evaluation of specific cytokines and chemokines) and incident DM.MethodsParticipants were adults with physician-confirmed RA from Veteran’s Affairs Rheumatoid Arthritis Registry. Disease activity and clinical assessments occur longitudinally as part of clinical care. Thirty cytokines and chemokines were measured in banked serum obtained at the time of enrolment. Cytokine/chemokine values were log-adjusted and standardised (per SD). Incident DM was defined based on validated algorithms using diagnostic codes and medications. Multivariable Cox proportional hazard models evaluated associations between clinical factors and incident DM. Independent associations between cytokines/chemokines and incident DM were assessed adjusting for age, sex, race, smoking, body mass index (BMI) and medication use at baseline.ResultsAmong 1866 patients with RA without prevalent DM at enrolment, there were 130 incident cases over 9223 person-years of follow-up. High Disease Activity Score (DAS28)-C reactive protein (CRP), obese BMI, older age and male sex were associated with greater risk for incident DM while current smoking and methotrexate use were protective. Patients using methotrexate were at lower risk. Several cytokines/chemokines evaluated were independently associated (per 1 SD) with DM incidence including interleukin(IL)-1, IL-6 and select macrophage-derived cytokines/chemokines (HR range 1.11–1.26). These associations were independent of the DAS28-CRP.ConclusionsHigher disease activity and elevated levels of cytokines/chemokines are associated with a higher risk of incident DM in patients with RA. Future study may help to determine if targeted treatments in at-risk individuals could prevent the development of DM.

Purpose Studies of the relation of fibromyalgia (FM) and widespread pain (WSP) to mortality have differed as to the presence or absence of an association and the extent of cause-specific mortality. However, no studies have investigated which definitions of FM and WSP associate with mortality, nor of FM mortality in other diseases. We investigated these issues and the meaning of mortality in patients with FM. Methods We used Cox regression to study 35,248 rheumatic disease patients with up to 16 years of mortality follow-up in all patients and separately in those with diagnoses of rheumatoid arthritis (RA) (N = 26,458), non-inflammatory rheumatic disorders (NIRMD) (N = 5,167) and clinically diagnosed FM (N = 3,659). We applied 2016 FM criteria and other FM and WSP criteria to models adjusted for age and sex as well as to models that included a full range of covariates, including comorbid disease and functional status. We estimated the degree of explained of variance (R2) as a measure of predictive ability. Results We found positive associations between al`l definitions of FM and WSP and all-cause mortality, with relative risks (RR)s ranging from 1.19 (95%CI 1.15–1.24) for American College of Rheumatology (ACR) 1990 WSP to 1.38 (1.31–1.46) in age and sex adjusted revised 2016 criteria (FM 2016). However, in full covariate models the FM 2016 RR reduced further to 1.15 (1.09–1.22). The association with mortality was noted with RA (1.52 (1.43–1.61)), NIRMD (1.43 (1.24–1.66)) and clinical FM (1.41 (1.14–1.75) - where 37% of FM diagnosed patients did not satisfy FM 2016 criteria. In the all-patient analyses, the age and sex explained variation (R2) was 0.255, increasing to 0.264 (4.4%) when FM 2016 criteria were added, and to 0.378 in a full covariate model. Death causes related to FM 2016 status included accidents, 1.45 (1.11–1.91); diabetes 1.78 (1.16–2,71); suicide, 3.01 (1.55–5.84) and hypertensive related disorders, 3.01 (1.55–5.84). Cancer deaths were less common 0.77 (0.68–0.88). Conclusions FM is weakly associated with mortality within all criteria definitions of FM and WSP examined (3.4% of explained variance), and across all diseases (RA, NIRMD, clinical FM) equally. Clinical and criteria-defined FM had different mortality outcomes. We found no evidence for a positive association of cancer and FM or WSP.

Objective: Recognizing that the interrelationships between chronic conditions that complicate rheumatoid arthritis (RA) are poorly understood, we aimed to identify patterns of multimorbidity and to define their prevalence in RA through machine learning. Methods: We constructed RA and age- and gender-matched (1:1) non-RA cohorts within a large commercial insurance database (MarketScan®) and the Veterans Health Administration (VHA). Chronic conditions (n=44) were identified from diagnosis codes from outpatient and inpatient encounters. Exploratory factor analysis was performed separately in both databases, stratified by RA diagnosis and sex, to identify multimorbidity patterns. The association of RA with different multimorbidity patterns was determined using conditional logistic regression. Results: We studied 226,850 patients in MarketScan® (76% female) and 120,780 patients in the VHA (89% male). The primary multimorbidity patterns identified were characterized by the presence of cardiopulmonary, cardiometabolic, and mental health and chronic pain disorders. Multimorbidity patterns were similar between RA and non-RA patients, females and males, MarketScan® and the VHA. RA patients had higher odds of each multimorbidity pattern (odds ratios [ORs] 1.17 to 2.96), with mental health and chronic pain disorders being the multimorbidity pattern most strongly associated with RA (ORs 2.07 to 2.96). Conclusions: Cardiopulmonary, cardiometabolic, and mental health and chronic pain disorders represent predominant multimorbidity patterns, each of which are over-represented in RA. The identification of multimorbidity patterns occurring more frequently in RA is an important first step in progressing toward a holistic approach to RA management and warrants assessment of their clinical and predictive utility.

ObjectiveThis study evaluated associations between fibroblast growth factor (FGF)-21, an adipokine associated with metabolic stress, and adverse longitudinal changes in body composition and physical functioning in patients with rheumatoid arthritis (RA).MethodsAt baseline and follow-up, patients with RA aged 18–70 years completed whole-body dual-energy X-ray absorptiometry and peripheral quantitative computed tomography to quantify lean mass, fat mass, and muscle density. Dynamometry assessed muscle strength at the hand and knee, and physical functioning was measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). FGF-21 and inflammatory cytokines were measured at baseline. Linear and logistic regression analyses assessed associations between FGF-21 levels and both body composition and physical functioning over time.ResultsThere were 113 patients with RA enrolled, and 84 (74%) returned for follow-up at a median of 2.68 years. At baseline, FGF-21 was associated with age, smoking, methotrexate use, adiposity, and inflammatory cytokines: tumor necrosis factor receptor type I, YKL-40, vascular endothelial growth factor (VEGF), and resistin. The highest FGF-21 quartile was associated with worse SPPB and HAQ. Higher baseline FGF-21 levels (per 1 SD) were associated with worsening in muscle density and area Z-scores (β –0.06, 95% CI –0.12 to 0.008, P = 0.08; and β –0.05, 95% CI –0.10 to 0.006, P = 0.08, respectively) and a greater probability of a clinically meaningful worsening of HAQ (OR 2.37, 95% CI 1.21–4.64, P = 0.01). The fourth FGF-21 quartile was associated with worsening of SPPB (β –0.57, 95% CI –1.04 to –0.09, P = 0.02).ConclusionFGF-21 levels are associated with obesity and inflammatory cytokines, and with worsening in physical functioning in RA. These data support the hypothesis that FGF-21 can identify patients at risk of functional decline.

OBJECTIVE To determine the performance of administrative-based algorithms for classifying interstitial lung disease (ILD) complicating rheumatoid arthritis (RA). METHODS Participants in a large, multicenter RA registry were screened for ILD using codes from the International Classification of Diseases, Ninth Revision (ICD-9) and the ICD-10. Medical record review confirmed ILD among participants screening positive and a random sample of those screening negative. ICD and procedure codes, provider specialty, and dates were extracted from Veterans Affairs administrative data to construct ILD algorithms. Performance of these algorithms against medical record review was assessed by sensitivity, specificity, positive predictive value (PPV), negative predictive value, and kappa using inverse probability weighting to account for sampling methods. RESULTS Medical records of 536 RA patients were reviewed, confirming 182 (stringent definition) and 203 (relaxed definition) cases of ILD. Initially, we identified ≥2 ICD codes from inpatient or outpatient encounters as optimal discriminating factors (specificity 96.0%, PPV 65.5%; κ = 0.70). Subsequently, we constructed a set of ICD-9 and ICD-10 codes that improved algorithm specificity (specificity 96.8%, PPV 69.5%; κ = 0.72). Algorithms that included a pulmonologist diagnosis or chest computed tomography plus pulmonary function testing or lung biopsy had improved performance (specificity 98.0%, PPV 77.4%; κ = 0.75). PPV increased with exclusion of other ILD causes (78.5%) in comparison with the relaxed ILD definition (82.4%) and in sensitivity analyses (83.4-86.3%). Gains in specificity and PPV with greater algorithm requirements were accompanied by declines in sensitivity. CONCLUSION Administrative algorithms with optimal combinations of ICD codes, provider specialty, diagnostic testing, and exclusion of other ILD causes accurately classify ILD in RA.