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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

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.

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.

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. 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.

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 examine the relationship of posttraumatic stress disorder (PTSD) with earlier treatment discontinuation and medication adherence in US veterans with rheumatoid arthritis (RA). Methods Veterans Affairs (VA) administrative data (2005-2014) were used to define unique dispensing episodes of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) for veterans with RA. Diagnosis codes were used to categorize patients into mutually exclusive groups: PTSD (with/without depression/anxiety), depression/anxiety without PTSD, and neither psychiatric diagnosis. Multivariable Cox proportional hazards models were used to evaluate associations between psychiatric diagnoses and time to disease-modifying antirheumatic drug discontinuation (lapse in refill >90 days). Multivariable logistic regression was used to examine associations of diagnoses with medication nonadherence (proportion of days covered Results There were 15 081 dispensing episodes of MTX and 8412 dispensing episodes of TNFi. PTSD was independently associated with a greater likelihood of earlier discontinuation of both MTX (hazard ratio [HR] 1.15 [1.10-1.21]) and TNFi (HR 1.20 [1.13-1.28]). Depression/anxiety had a comparable risk of discontinuation for both MTX (HR 1.14 [1.10-1.19]) and TNFi (HR 1.16 [1.10-1.22]). Depression/anxiety, but not PTSD, was associated with higher odds of MTX (odds ratio [OR] 1.12 [1.03-1.22]) and TNFi (OR 1.14 [1.02-1.27]) nonadherence. Conclusion Veterans with RA and comorbid PTSD, depression, or anxiety had poor persistence of MTX and TNFi therapies. These results suggest that earlier discontinuation and low adherence to therapy among patients with RA with these psychiatric comorbidities may contribute to worse disease outcomes. Mechanisms by which these comorbidities contribute to lower adherence deserve further investigation and may lead to targeted interventions to improve disease outcomes.

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.

Objective Objectives of this study were to describe exercise patterns among patients with inflammatory arthritis (IA) in four recommended domains (Aerobic, Resistance, Flexibility, Balance), identify exercise barriers and facilitators, and explore patients’ perceptions of interactions with rheumatology providers about exercise. Methods Patients with IA at a single academic medical center were invited to complete a survey about exercise. Patients were recruited for a paper‐based survey prior to appointments or a web‐based study through the electronic health record if they had been seen in the practice within the past year. Respondents reporting minimum aerobic exercise plus at least one other domain were categorized as “Active,” and the remaining as “Inactive.” Survey responses were compared between groups. Results Of 1113 invited, 108 completed the survey. Among these, 60 (56%) reported aerobic exercise, 44 (41%) flexibility, 42 (39%) resistance, and 18 (17%) balance. Forty‐three (40%) were categorized as active, 65 (60%) inactive. The active group had lower body mass index, lower reported disease activity, and fewer comorbidities. Active patients reported more self‐efficacy, prioritized exercise, improved energy, exercising for weight control, and exercise before arthritis diagnosis (all P < .05). The inactive group cited finances, pain, fatigue, and potentially worsening arthritis as barriers (all P < .05). Most understood the benefits of exercise. Few perceived that exercise recommendations were addressed by their providers. Conclusion Approximately half of patients reported regular aerobic exercise; fewer regularly engaged in other types of physical activity. Patients do not perceive they have received exercise guidance from providers, which suggests an opportunity for more prescriptive exercise discussions.

Background This study aims to assess the construct validity of a body composition-defined definition of sarcopenic obesity based on low appendicular lean mass relative to fat mass (ALMIFMI ) and high fat mass index (FMI) and to compare with an alternative definition using appendicular lean mass index (ALMI) and percent body fat (%BF). Methods This is a secondary analysis of two cohort studies: the National Health and Examination Survey (NHANES) and the Health, Aging, and Body Composition study (Health ABC). Sarcopenic obesity was defined as low ALMIFMI combined with high FMI and was compared with a widely used definition based on ALMI and %BF cut-points. Body composition Z-scores, self-reported disability, physical functioning, and incident disability were compared across body composition categories using linear and logistic regression and Cox proportional hazards models. Results Among 14, 850 participants from NHANES, patients with sarcopenic obesity defined by low ALMIFMI and high FMI (ALMIFMI -FMI) had above-average FMI Z-scores [mean (standard deviation): 1.00 (0.72)]. In contrast, those with sarcopenic obesity based on low ALMI and high %BF (ALMI-%BF) had below-average FMI Z-scores. A similar pattern was observed for 2846 participants from Health ABC. Participants with sarcopenic obesity based on ALMIFMI -FMI had a greater number of disabilities, worse physical function, and a greater risk of incident disability compared with those defined based on ALMI-%BF. Conclusions Body composition-defined measures of sarcopenic obesity defined as excess adiposity and lower-than-expected ALMI relative to FMI are associated with functional deficits and incident disability and overcome the limitations of using %BF in estimating obesity in this context.

Introduction Prior studies have identified associations between obesity and numerous conditions that increase risks for chronic pain. However, the impact of obesity on prescription opioid use is not well known. This study investigates the association between obesity and incidence of long-term prescription opioid use. Methods Fifteen panels of the Medical Expenditure Panel Survey from 2000 to 2015 were pooled to generate a sample of civilian non-institutionalized adults aged 30–84 years who were prescription opioid–naive for approximately 9 months. Incident long-term prescription opioid use was defined as reporting use at 2 of 3 interviews during a 15-month follow-up. BMI was reported at baseline. Analyses were completed in 2019. Results Among opioid–naive adults (n=89,629), obesity was strongly associated with incident long-term prescription opioid use. The association increased at progressively higher BMI values, with 24% elevated odds (95% CI=7%, 44%) in adults with overweight (25–29.9 kg/m2) and 158% increased odds (95% CI=106%, 224%) among adults with Class III obesity (40–49.9 kg/m2). These associations grew with higher-dosage opioids. Of the reasons for opioid use, joint pain, back pain, injury, and muscle/nerve pain contributed the most to the excess use observed among adults with obesity. At the population level, 27.0% of incident long-term prescription opioid use (95% CI=19.0%, 34.8%) was attributable to adults having a BMI above normal weight (25–49.9 kg/m2). Conclusions These findings suggest that obesity has contributed to prescription opioid use in the U.S. Future investments in chronic pain reduction may benefit from increased integration with obesity prevention and treatment.

Rheumatoid arthritis (RA) is an inflammatory disease that leads to altered body composition. The loss of lean mass with a preservation or increase in fat mass has been termed rheumatoid cachexia (RC), to contrast with classic cachexia, which is characterized by severe weight loss. There are limited data on the prevalence and progression of cachexia in RA over time, as well as on associated factors. Our aim was to determine the prevalence of cachexia and to determine associations with potential factors. This prospective cohort study recruited consecutively patients diagnosed with RA and followed for 1 year. The assessments were performed: clinical features, body composition, and physical function. RC and classic cachexia were assessed by several established diagnostic criteria. The pairwise Student’s t test, Chi-square test, and GEE were performed (accepted at p ≤ 0.05). Of 90 patients recruited, 81 completed the study. Most patients were women (88.9%), and the mean age was 56.5 ± 7.3 years. At baseline, the median DAS28-CRP was 3.0 (IQR, 1.0–3.0), 13.3–30.0% of the included patients had RC, while none met criteria for classic cachexia. The prevalence of cachexia did not change after 12 months. Disease activity status and treatment with biologic disease-modifying antirheumatic drugs were significantly associated with changes on body composition and physical function (p

OBJECTIVE: In rheumatoid arthritis, whether women are less likely to achieve low disease activity is unclear. We evaluated sex differences in remission and low disease activity, comparing different clinical and imaging measures.METHODS: We used data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry and from 2 clinical trials. Remission and low disease activity were defined using composite scores, individual items (tender joints, swollen joints, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP] level, and evaluator/patient global assessment), and magnetic resonance imaging (MRI). In the VARA registry, we assessed the likelihood of point remission at any time during follow-up using logistic regression, and time to sustained remission (2 consecutive visits) using Cox proportional hazards models. In the clinical trials, logistic regression models evaluated the likelihood of low clinical and MRI activity at 52 weeks.RESULTS: Among 2,463 patients in VARA, women (10.2%) were less likely to be in Disease Activity Score in 28 joints (DAS28)-ESR remission in follow-up (odds ratio [OR] 0.71 [95% confidence interval (95% CI) 0.55-0.91]; P < 0.01) and had a longer time to sustained DAS28-ESR remission. This difference was not observed for DAS28-CRP, Clinical Disease Activity Index, or Routine Assessment of Patient Index Data 3. Women were more likely to achieve favorable individual components except for an ESR CONCLUSION: The comparison of remission rates between men and women varies based on the disease activity measure, with sex-specific differences in ESR resulting in reliably lower rates of remission among women. There were no differences in MRI measures.

OBJECTIVE Better disease activity and quality of life have been observed among patients with rheumatoid arthritis (RA) who drink alcohol. This association might be explained by reverse causality. We undertook this study to identify predictors of change in alcohol use and to evaluate independent associations between alcohol use and RA activity and mortality. METHODS Participants in Forward, The National Databank for Rheumatic Diseases, were asked about alcohol use (any versus none), and disease activity was collected through the Patient Activity Scale-II (PAS-II) on semiannual surveys. We identified factors associated with changes in alcohol use and determined associations between alcohol use and disease activity and mortality using linear and logistic regression models, Cox proportional hazards models, and marginal structural models. RESULTS A total of 121,280 observations were studied among 16,762 unique participants. Discontinuation and initiation of alcohol were common among drinkers and abstainers (8.2% and 9.2% of observations, respectively). Greater discontinuation and less initiation were observed with greater disease activity, older age, female sex, nonwhite race, obesity, greater comorbidity, low quality of life, low educational level, low income, and work disability. While alcohol users had lower PAS-II (β = -0.15 [95% confidence interval (95% CI) -0.18, -0.11], P < 0.001) and a lower mortality (odds ratio 0.87 [95% CI 0.76, 0.98], P = 0.03) in traditional models, associations were not seen in marginal structural models. CONCLUSION Higher disease activity, disability, comorbidity, and poor quality of life contribute to reductions in alcohol use. Active use and changes in use were not associated with disease activity or mortality when adjusting for confounding, suggesting no clear benefit of alcohol consumption in RA.

OBJECTIVE To investigate whether magnetic resonance imaging (MRI) pathologies in the wrist/hand of rheumatoid arthritis (RA) patients are associated with patient-reported outcomes (PROs) at clinical remission and relapse. METHODS Wrist/hand MRIs and wrists/hands/feet radiographs were obtained in 114 established RA patients in clinical remission, before tapering their biologic disease-modifying antirheumatic drugs. MRIs were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI score (RAMRIS) for inflammation (synovitis/tenosynovitis/bone marrow edema) and damage (bone erosion/joint space narrowing) at baseline (ie remission) and in case of a relapse (n = 70). Radiographs were assessed according to the Sharp/van der Heijde (SvH) method at baseline. These scores were assessed for associations with health assessment questionnaires (HAQ), visual analog scales (VAS global/pain), EuroQol-5 dimensions and Short-Form 36 physical and mental component summary (SF-36 PCS/MCS) using Spearman correlations, univariate/multivariable linear regression analyses and generalized estimating equations. Furthermore, MRI pathologies were assessed for association with specific hand-related HAQ items using Jonckheere trend tests. RESULTS Magnetic resonance imaging-assessed damage was associated with impaired HAQ and SF-36 PCS at remission and relapse (P

OBJECTIVE: Obesity, defined by body mass index (BMI, kg/m(2)), is associated with lower mortality risk in numerous chronic disease states, a phenomenon termed the obesity paradox. Indices of obesity, including BMI and % body fat are confounded by muscle mass, while DXA-derived fat mass index (kg/m(2)) is not. We compared the associations between obesity and mortality in persons with chronic kidney disease (CKD) using several estimates of obesity, including fat mass index, and determined whether muscle mass, inflammation and weight loss modify these associations. DESIGN: Retrospective cohort study SETTING AND SUBJECTS: 2,852 NHANES participants from 1999–2006, aged 20 years or more with body composition measures and CKD defined as estimated glomerular filtration rate 10% weight loss was 20% in participants that were obese by fat mass index, compared with 40% in the remainder. Prior weight loss was associated with mortality, and the protective association of obesity was no longer significant after adjustment for prior weight loss. Inflammation did not modify these associations. CONCLUSIONS: An apparent protective association of high fat mass was seen in chronic kidney disease, particularly among persons with lower muscle mass. The prevalence of prior weight loss was two-fold lower among obese compared to non-obese persons, confounding these associations.

BACKGROUND Low-dose glucocorticoids are commonly used in the treatment of rheumatoid arthritis (RA). Observational studies have found an increased risk of serious infection associated with low-dose glucocorticoids, but concerns about residual confounding remain. METHODS We identified adults with RA on stable immunomodulatory therapy for >6 months receiving no glucocorticoids or ≤5 mg/day using Medicare data from 2006 to 2015. We used provider preference for glucocorticoids as an instrumental variable (IV) to assess associations between low-dose glucocorticoid use and the risk of infection requiring hospitalization using a cause-specific proportional hazards model. RESULTS We identified 163,603 qualifying treatment episodes among 120,656 patients. Glucocorticoids ≤5 mg/day were used by 25,373/81,802 (31.0%) of patients seen by a rheumatologist with low provider preference for glucocorticoids and by 36,087/81,801 (44.1%) of patients seen by a rheumatologist with high provider preference for glucocorticoids (adjusted odds ratio 1.81, 95% confidence interval 1.77, 1.84 for association between provider preference and glucocorticoids). Chronic obstructive pulmonary disease, opioids, antibiotics, previous emergency department visits, hospitalizations, and infections requiring hospitalization infections were unbalanced with regard to exposure but not to the IV. The incidence of infection requiring hospitalization was 8.0/100 person-years among patients unexposed to glucocorticoids versus 11.7/100 person-years among those exposed. The association between glucocorticoids and infection requiring hospitalization from IV analysis (hazard ratio 1.26 [1.02-1.56]) was similar to results from a standard multivariable model (hazard ratio 1.24 [1.21-1.28]). CONCLUSIONS Among patients with RA on stable immunomodulatory therapy, IV analysis based on provider preference demonstrated an increased risk of infection requiring hospitalization associated with low-dose glucocorticoids, similar to a traditional analysis.

We determined associations between adipokines and abnormal body composition in patients with rheumatoid arthritis (RA).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).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).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.

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide general guidance for commonly encountered clinical scenarios. The recommendations do not dictate the care for an individual patient. The ACR considers adherence to the recommendations described in this guideline to be voluntary, with the ultimate determination regarding their application to be made by the clinicians in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice. ACR recommendations are not intended to dictate payment or insurance decisions, or drug formularies or other third-party analyses. Third parties that cite ACR guidelines should state that these recommendations are not meant for this purpose. These recommendations cannot adequately convey all uncertainties and nuances of patient care. The American College of Rheumatology is an independent, professional, medical and scientific society that does not guarantee, warrant, or endorse any commercial product or service. OBJECTIVE. To develop updated guidelines for the pharmacologic management of rheumatoid arthritis. METHODS. We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS. The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional). CONCLUSION. This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients’ values, goals, preferences, and comorbidities.

As reporting of COVID‐19 at the US state level has become more granular, many states have reported a higher proportion of deaths among African‐Americans. In our study, we assessed state level data on race, population density, age, obesity rates, insurance data, GDP, per capita healthcare resources (hospital‐beds/ventilators per‐capita), median household income and high‐school graduation rates. We report a higher death rate among states with a greater proportion of African‐American residents despite adjusting for case rates and state‐level factors. To the best of our knowledge this is the first study looking at state level data (from across the US) and mortality with COVID‐19. This article is protected by copyright. All rights reserved.

Objective Although post-traumatic stress disorder (PTSD) is identified as a risk factor in the development of rheumatoid arthritis (RA), associations of PTSD with disease progression are less clear. To explore whether PTSD might influence disease-related measures of systemic inflammation in RA, we compared serum cytokine/chemokine (cytokine) concentrations in RA patients with and without PTSD. Methods Participants were U.S. Veterans with RA and were categorized as having PTSD, other forms of depression/anxiety, or neither based on administrative diagnostic codes. Multiplex cytokines were measured using banked serum. Associations of PTSD with cytokine parameters (including a weighted cytokine score) were assessed using multivariable regression, stratified by anti-CCP status and adjusted for age, sex, race, and smoking status. Results Among 1,460 RA subjects with mean (SD) age of 64 (11) years and disease duration of 11 (11) years, 91% were male, 77% anti-CCP positive, and 80% ever smokers. Of these, 11.6% had PTSD, 23.7% other depression/anxiety, and 64.7% had neither. PTSD, but not depression/anxiety, was associated with a higher cytokine score and number of high-concentration analytes in adjusted models, though this was limited to anti-CCP positive subjects. PTSD was associated with heightened expression of several individual cytokines including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-17, IFN-γ, GM-CSF, MCP-1, and TNF-α. Conclusion Anti-CCP positive RA patients with PTSD have higher serum cytokine concentrations than those without PTSD, demonstrating that systemic inflammation characteristic of RA is heightened in the context of this relatively common psychiatric comorbidity.

Introduction Magnetic resonance imaging (MRI) is increasingly used in patients with rheumatoid arthritis (RA) to determine residual inflammation after treatment and as a predictor of structural damage progression. Establishing an optimal threshold of inflammatory activity that predicts lower risk of structural damage progression may inform treatment decisions. This post hoc analysis investigated whether patients with RA at low risk of structural damage progression can be identified based on MRI inflammation thresholds. Methods Hand and wrist MRI was performed at baseline, and at months 6 and 12 in a phase 3b, randomized, active-controlled, double-blind trial of abatacept in early RA (AVERT). Pathologies were scored using the OMERACT RA MRI Score. Data were stratified into two risk subgroups (less and more severe inflammation) for structural damage progression (erosion change > 0.5) based on baseline inflammation. In this post hoc analysis, log odds ratios of probability of progression {adjusted for baseline Disease Activity Score in 28 joints [C-reactive protein; DAS28 (CRP)]} were compared between subgroups to test the performance of inflammation thresholds. Results There were 351 randomized and treated patients with baseline MRIs, of whom 276 (78.6%) and 235 (67.0%) had MRIs available at months 6 and 12, respectively. The DAS28 (CRP)-adjusted probabilities of progression from baseline to month 12 based on scores at baseline, and from months 6 to 12 based on month 6 scores, were significantly lower among patients with less inflammation (P

PURPOSE OF REVIEW: Patients with rheumatoid arthritis are at increased risk of infection after surgery. Recent literature has provided more data and updated guidelines to guide the management of immunosuppression in the perioperative period. RECENT FINDINGS: Studies over the past few years have confirmed that patients with rheumatoid arthritis are at increased risk of infection after surgery. Patients treated with biologics are at greater risk of post-operative infection, but this risk might be explained by the comorbidities and greater disease severity often seen in these patients. Recent observational studies have suggested that interruption of biologic therapies before surgery may not be associated with better outcomes. Glucocorticoids, however, have consistently been found to be risk factors for infection. Recent guidelines from the American College of Rheumatology/American Association of Hip and Knee Surgeons recommend continuing conventional disease modifying drugs and holding biologics for one dosing interval before surgery. SUMMARY: Prolonged interruption of conventional and biologic therapies before surgery does not appear to substantially reduce infection risk. Guidelines now recommend continuing conventional DMARDs and holding biologics for just one dosing interval before surgery. Glucocorticoids are strongly associated with the risk of post-operative infection and should be minimized before surgery.

Background Conventional definitions of sarcopenia based on lean mass may fail to capture low lean mass relative to higher fat mass, that is, relative sarcopenia. The objective of this study is to determine the associations of sarcopenia and relative sarcopenia with mortality independent of co‐morbidities, and whether chronic kidney disease (CKD) and adiposity alter these associations. Methods Dual energy X‐ray absorptiometry‐derived appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI, kg/m2) were assessed in 14 850 National Health and Nutrition Examination Survey participants from 1999 to 2006 and were linked to death certificate data in the National Death Index with follow‐up through 2011. Sarcopenia was defined using sex‐specific and race/ethnicity‐specific standard deviation scores compared with young adults (T‐scores) as an ALMI T‐score

Objective Rheumatoid arthritis (RA) is associated with adverse body composition profiles and low muscle density due to the accumulation of intramuscular fat. Linear regression was used to assess differences between RA patients and controls and to determine associations between muscle density, strength, and physical functioning. Methods Patients with RA, ages 18-70 years, and healthy control subjects underwent whole-body dual x-ray absorptiometry and peripheral quantitative computed tomography, in order to quantify the appendicular lean mass index (ALMI) and the fat mass index (FMI), visceral fat area, and muscle density. Dynamometry was used to measure hand grip strength and muscle strength at the knee and lower leg. Disability and physical functioning were measured using the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). Linear regression analyses were performed to assess differences related to RA and associations between muscle density, strength, and function. Results The study group included 103 patients with RA (51 men) and 428 healthy control subjects. Among patients with RA, low muscle density was associated with higher disease activity, C-reactive protein and interleukin-6 levels, greater total and visceral fat area, lower ALMI Z scores, physical inactivity, and long-term use of glucocorticoids (>1 year). Patients with low ALMI Z scores had lower muscle density Z scores compared with reference participants with similarly low ALMI scores. Low muscle density was independently associated with lower muscle strength, higher HAQ scores, and lower SPPB scores, after adjustment for ALMI and FMI Z scores. Conclusion The low muscle density observed in patients with RA was associated with low muscle mass, excess adiposity, poor strength, and greater disability. Interventions to address poor muscle quality could potentially affect important functional outcomes.

OBJECTIVES: We aimed to assess whether serum cytokine/chemokine concentrations predict incident cancer in RA patients. METHODS: Data from cancer-free enrollees in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry were linked to a national VA oncology database and the National Death Index (NDI) to identify incident cancers. Seventeen serum cytokines/chemokines were measured from enrollment serum and an overall weighted cytokine/chemokine score (CK score) was calculated. Associations of cytokines/chemokines with all-site, lung, and lymphoproliferative cancers were assessed in Cox regression models accounting for relevant covariates including age, sex, RA disease activity, and smoking. RESULTS: In 1,216 patients, 146 incident cancers (42 lung and 23 lymphoproliferative cancers) occurred over 10,072 patient-years of follow-up with a median time of 4.6 years from enrollment (cytokine/chemokine measurement) to cancer incidence. In fully adjusted models, CK score was associated with a higher risk of all-site (aHR 1.32, 95% CI 1.01-1.71, p

Rationale: Prior studies investigating associations of rheumatoid factor (RF) and anti–citrullinated protein antibody (ACPA) seropositivity with risk for rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) have mostly used cross-sectional or case–control designs. Objectives: To determine whether combined autoantibody seropositivity and higher individual autoantibody concentrations were associated with increased risk for RA-ILD in a prospective RA cohort. Methods: Within the Veterans Affairs Rheumatoid Arthritis prospective registry, we performed a cross-sectional study of prevalent ILD and a retrospective cohort study of incident ILD (diagnosed after at least 12 mo of longitudinal follow-up). We used logistic and Cox regression methods to determine whether combined RF/ACPA seropositivity and higher autoantibody concentrations were independently associated with greater risk for prevalent and incident ILD, respectively. Results: Among 2,328 participants (median age 64 yr, 89.3% male), 100 (4.3%) subjects had prevalent ILD at enrollment. During 14,281 patient-years of follow-up, 83 (3.7%) of the remaining 2,228 were subsequently diagnosed with incident ILD (5.8 cases per 1,000 person-years). Patients with combined RF/ACPA seropositivity had a higher probability of prevalent ILD compared with seronegative subjects (odds ratio [OR], 2.90; 95% confidence interval [CI], 1.24–6.78). RF titers demonstrated a monotonic association with prevalent ILD (OR, 2.69; 95% CI, 1.11–6.51 for low-positive [15–45 IU/ml] titers; OR, 3.40; 95% CI, 1.61–7.18 for high-positive [>45 IU/ml] titers; P for trend 0.01). Patients with high-positive (>15 U/ml) ACPA titers were also at higher risk for prevalent ILD (OR, 1.91; 95% CI, 1.04–3.49) compared with ACPA-negative subjects. Combined RF/ACPA seropositivity was not associated with increased risk for incident ILD, nor were high- or low-positive RF or ACPA titers. In a piecewise linear spline model, however, RF titers greater than 90 IU/ml independently correlated with increased risk for incident ILD (hazard ratio, 1.68, 95% CI, 1.02–2.77). Conclusions: Combined RF/ACPA seropositivity and individual autoantibody concentrations were strongly associated with prevalent but not incident RA-ILD. Only patients with RF concentrations >90 IU/ml were observed to be at higher risk of incident RA-ILD.

We were pleased to read the commentary on our recent article by Ruscitti et al and we share their interest in the potential role of inflammatory pathways in the development of metabolic disorders such as diabetes in patients with rheumatoid arthritis (RA).1 Indeed, both interleukin (IL)-1 and IL-6 levels were independently associated with the development of diabetes in our original study, implicating them as potential mediators of metabolic changes that could lead to the development of diabetes.2 Observational research is, of course, limited to defining associations and cannot prove causality. In our study, as in many large observational studies, we were unable to assess total adiposity or to assess visceral fat content; factors that play an important role in diabetes risk …

ObjectiveExamine the association of methotrexate (MTX) use with cardiovascular disease (CVD) in rheumatoid arthritis (RA) using marginal structural models (MSM) and determine if CVD risk is mediated through modification of disease activity.MethodsWe identified incident CVD events (coronary artery disease (CAD), stroke, heart failure (HF) hospitalisation, CVD death) within a multicentre, prospective cohort of US Veterans with RA. A 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) was collected at regular visits and medication exposures were determined by linking to pharmacy dispensing data. MSMs were used to estimate the treatment effect of MTX on risk of incident CVD, accounting for time-varying confounders between receiving MTX and CVD events. A mediation analysis was performed to estimate the indirect effects of methotrexate on CVD risk through modification of RA disease activity.ResultsAmong 2044 RA patients (90% male, mean age 63.9 years, baseline DAS28-CRP 3.6), there were 378 incident CVD events. Using MSM, MTX use was associated with a 24% reduced risk of composite CVD events (HR 0.76, 95% CI 0.58 to 0.99) including a 57% reduction in HF hospitalisations (HR 0.43, 95% CI 0.24 to 0.77). Individual associations with CAD, stroke and CVD death were not statistically significant. In mediation analyses, there was no evidence of indirect effects of MTX on CVD risk through disease activity modification (HR 1.03, 95% CI 0.80 to 1.32).ConclusionsMTX use in RA was associated with a reduced risk of CVD events, particularly HF-related hospitalisations. These associations were not mediated through reductions in RA disease activity, suggesting alternative MTX-related mechanisms may modify CVD risk in this population.

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease associated with increased risk of atherosclerosis. Leptin may indirectly contribute to atherogenesis, but its role in RA is not clear. Hypothesis: We aimed to study the correlation between leptin and inflammation in the abdominal aorta (AA) assessed by 18F-FDG PET/CT in RA patients. Methods: We retrospectively analyzed the data of 18 RA patients (mean age 56.0±11.9, 14 male). All patients were administered 18F-FDG intravenously, and full-body PET/CT scans were acquired 180 minutes later. Regions of interest were delineated around the wall of the AA, with a superior border at the aortic hiatus of the diaphragm and an inferior border at the bifurcation of iliac arteries. Mean standard uptake values per axial slice were averaged to calculate the average SUVmean (aSUVmean). BMI, visceral fat area (VFA), and serum logarithmically transformed leptin (ln-leptin) were obtained. Patients were divided into low- and high-BMI groups, with a cutoff of 25 kg/m2. Results: Mean BMI (kg/m2) and VFA (cm2) between the low- and high-BMI groups were 21.7 vs. 31.4 (p Conclusion: In our study, higher serum leptin levels moderately correlated with 18F-FDG uptake in the AA, which reflects inflammation and atherogenic activity. Future studies are warranted to further elucidate the role of leptin in co-morbid atherosclerosis in patients with RA.

ObjectiveTo assess concerns and healthcare-related behaviors of patients with autoimmune rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic.MethodsAdults from the United States with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and systemic lupus erythematosus (SLE) from the ArthritisPower Patient-Powered Research Network and CreakyJoints patient community completed surveys. Concerns and behaviors were compared among patients with different autoimmune conditions, disease-modifying antirheumatic drug (DMARD) use, and geographic measures of urban status, income, education, and COVID-19 activity.ResultsAmong 1517 participants (925 RA, 299 PsA, 185 AS, 108 SLE), mean age was 55.1 years, 88.3% were female, and 89.5% were White. COVID-19 concerns were similar across the country and were higher in biologic users (P < 0.001). Avoidance of doctor’s office visits (56.6%) or laboratory testing (42.3%) and use of telehealth (29.5%) were more common in urban areas. Among participants receiving a DMARD without COVID-19 or other respiratory illness, 14.9% stopped a DMARD, with 78.7% of DMARD interruptions not recommended by a physician. DMARD stopping was more common in participants with lower socioeconomic status (SES) and in participants who avoided an office visit (OR 1.46, 95% CI 1.04–2.04) or reported lack of telehealth availability OR 2.26 (95% CI 1.25–4.08).ConclusionIn the early months of the COVID-19 pandemic, patients with RA, PsA, AS, and SLE frequently avoided office visits and laboratory testing. DMARD interruptions commonly occurred without the advice of a physician and were associated with SES, office visits, and telehealth availability, highlighting the need for adequate healthcare access and attention to vulnerable populations during the pandemic.

PURPOSE: We assessed the impact of adjustment of the multi-biomarker disease activity score (MBDA) for age, sex, and leptin, over the range of age and adiposity, and assessed relationships with clinical disease activity. METHODS: Patients with RA, ages 18–75 years, were recruited from clinical practices and completed whole-body DXA to quantify fat mass indices (FMI, kg/m(2)). FMI Z-scores were calculated based on distributions in a reference population. Descriptive statistics described relationships between age, FMI Z-score, and the original MBDA and adjusted MBDA (aMBDA). Swollen joint counts (SJC) and the clinical disease activity index (CDAI) were assessed over MBDA categories. RESULTS: There were 104 participants (50% female) with mean (SD) age of 56.1 (12.5) and body mass index (BMI) of 28.8 (6.9). Older age was associated with higher MBDA scores in men. The aMBDA was not associated with age. The original MBDA score was associated with FMI Z-score among women (Rho = 0.42, p = 0.002) but not men. The aMBDA was not associated with FMI Z-score in either women or men. The aMBDA score was lower than the original MBDA in the highest quartile of FMI in women and was higher in the lowest FMI quartiles in women and men. CDAI, SJC, and radiographic scores were similar across activity categories for the original MBDA score and aMBDA. CONCLUSIONS: The aMBDA demonstrated reduced associations with adiposity, particularly among women. The aMBDA may be less likely to overestimate disease activity in women with greater adiposity and to underestimate disease activity in men and women with lesser adiposity.

BACKGROUND Low-dose glucocorticoids are frequently used for the management of rheumatoid arthritis (RA) and other chronic conditions, but the safety of long-term use remains uncertain. OBJECTIVE To quantify the risk for hospitalized infection with long-term use of low-dose glucocorticoids in patients with RA receiving stable disease-modifying antirheumatic drug (DMARD) therapy. DESIGN Retrospective cohort study. SETTING Medicare claims data and Optum's deidentified Clinformatics Data Mart database from 2006 to 2015. PATIENTS Adults with RA receiving a stable DMARD regimen for more than 6 months. MEASUREMENTS Associations between glucocorticoid dose (none, ≤5 mg/d, >5 to 10 mg/d, and >10 mg/d) and hospitalized infection were evaluated using inverse probability-weighted analyses, with 1-year cumulative incidence predicted from weighted models. RESULTS 247 297 observations were identified among 172 041 patients in Medicare and 58 279 observations among 44 118 patients in Optum. After 6 months of stable DMARD use, 47.1% of Medicare patients and 39.5% of Optum patients were receiving glucocorticoids. The 1-year cumulative incidence of hospitalized infection in Medicare patients not receiving glucocorticoids was 8.6% versus 11.0% (95% CI, 10.6% to 11.5%) for glucocorticoid dose of 5 mg or less per day, 14.4% (CI, 13.8% to 15.1%) for greater than 5 to 10 mg/d, and 17.7% (CI, 16.5% to 19.1%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). The 1-year cumulative incidence of hospitalized infection in Optum patients not receiving glucocorticoids was 4.0% versus 5.2% (CI, 4.7% to 5.8%) for glucocorticoid dose of 5 mg or less per day, 8.1% (CI, 7.0% to 9.3%) for greater than 5 to 10 mg/d, and 10.6% (CI, 8.5% to 13.2%) for greater than 10 mg/d (all P < 0.001 vs. no glucocorticoids). LIMITATION Potential for residual confounding and misclassification of glucocorticoid dose. CONCLUSION In patients with RA receiving stable DMARD therapy, glucocorticoids were associated with a dose-dependent increase in the risk for serious infection, with small but significant risks even at doses of 5 mg or less per day. Clinicians should balance the benefits of low-dose glucocorticoids with this potential risk. PRIMARY FUNDING SOURCE National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Background To determine whether initiation of a tumor necrosis factor inhibitor (TNFi) or methotrexate improves hemoglobin A1c in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS) who also have diabetes mellitus (DM). Methods A retrospective cohort study was conducted in Optum’s de-identified Clinformatics® Data Mart Database, an administrative claims database, using data from 2000 to 2014. Patients with PsA, RA, or AS, with DM (defined by ICD-9-CM codes) and/or HbA1c ≥7%, who newly initiated either a TNFi, MTX, or metformin (positive control) were identified. The change in HbA1c after drug initiation was calculated. Statistical differences in the change in HbA1c between drugs were assessed using the Wilcoxon rank sum test and linear regression models adjusting for potential confounders. Results Among 10,389 drug initiations in 9541 patients with PsA, RA, or AS, and available HbA1c values, HbA1c was ≥7 at baseline in 254 (35%) TNFi initiations, 361(37%) MTX initiations, and 2144 (50%) metformin initiations. Median HbA1c change was − 0.35 (IQR -1.10, 0.30) after TNFi initiation, − 0.40 (IQR -1.20, 0.30) after MTX initiation, and − 0.80 (IQR -1.60, − 0.10) after metformin initiation. In adjusted analyses, TNFi initiators had less of a decrease in HbA1c compared to MTX initiators (β 0.22, 95% CI: 0.004, 0.43), p = 0.046. Metformin initiators had a significantly greater decrease in HbA1c than MTX, β − 0.38 (95% CI: − 0.52, − 0.23), p Conclusion HbA1c decreased with TNFi initiation or MTX initiation. Reductions in HbA1c after initiation of a TNFi or MTX are about half (~ 0.4 units) the decrease observed after initiation of metformin.

PURPOSE OF THE REVIEW: A growing number of studies have suggested that disease outcomes and response to therapy may be different in patients with rheumatoid arthritis (RA) who are obese. The goal of this review is to examine the most recent literature, with a focus on the impact of obesity on the assessment of disease activity and treatment outcomes in RA. RECENT FINDINGS: Obesity is common in patients with RA and can have a substantial impact on patient symptoms and outcomes. Obesity is associated with higher rates of chronic pain and opiate use, elevated inflammatory markers, and less reliable physical exam findings, making assessment of disease activity and treatment response more challenging. Despite seemingly worse clinical disease activity, evidence has accumulated demonstrating that obese patients with RA have less inflammation by imaging and lower rates of radiographic progression over time. Whether obesity influences the effectiveness of specific therapies remains controversial. SUMMARY: Obesity is very common and is associated with more severe symptoms and higher rates of disability among RA patients. While clinical disease activity is frequently observed to be higher in obese patients with RA, it remains unclear whether poorer treatment response rates in this setting are related to reduced efficacy of therapies or are an artifact of biases in the accurate assessment of the disease.

Background Cyclooxygenase-2 (COX-2) has been found to be important for fracture-healing in animal models, raising concerns about use of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors after fractures. We evaluated associations of NSAIDs, COX-2 inhibitors, and opioids with nonunion after long-bone fracture. Methods Using private health insurance claims data from Optum's de-identified Clinformatics Data Mart database from January 1, 2000, to September 30, 2015, we identified adults with a single long-bone fracture or commonly paired long-bone fractures who had 1 year of available follow-up data. Using multivariable logistic regression models, we examined associations between NSAID, COX-2-inhibitor, or opioid prescription fills after the fracture and the risk of nonunion within 1 year, defined as a nonunion diagnosis with a procedure to treat the nonunion. Results A nonunion diagnosis with a procedure to treat the nonunion was identified after 2,996 (0.9%) of the 339,864 fracture episodes, with rates varying by fracture site. The risk of that outcome was greater in patients who had filled COX-2-inhibitor prescriptions (adjusted odds ratio = 1.84 [95% confidence interval = 1.38 to 2.46]) or opioid prescriptions (1.69 [1.53 to 1.86]), but not in patients who had filled nonselective-NSAID prescriptions (1.07 [0.93 to 1.23]) after the fracture. Results were similar when the outcome definition was changed to just a nonunion diagnosis. Conclusions COX-2 inhibitors, but not nonselective NSAIDs, were associated with a greater risk of nonunion after fracture. Opioids were also associated with nonunion risk, although patients filling prescriptions for opioids may have had more severe fractures. Level of evidence Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

OBJECTIVE: High magnetic resonance imaging (MRI)-detected inflammation is associated with greater progression and poorer outcomes in rheumatoid arthritis (RA). This analysis aimed to determine if baseline MRI inflammation was related to clinical response and remission in the Assessing Very Early Rheumatoid arthritis Treatment (AVERT) study.METHODS: AVERT was a phase IIIb, randomized, controlled trial with a 12-month, double-blind treatment period enrolling patients with early (≤2 years' duration), anti-citrullinated peptide-positive methotrexate (MTX)-naive RA. In this post hoc analysis, patients in the abatacept plus MTX (n = 114) and MTX (n = 111) arms with available MRI results were stratified into low and high baseline MRI inflammation groups based on previously developed cutoffs of synovitis and osteitis on unilateral hand-wrist contrast-enhanced MRI. Simplified Disease Activity Index (SDAI) remission (≤3.3), Clinical Disease Activity Index (CDAI) remission (≤2.8), Boolean remission, and Disease Activity Score in 28 joints using the C-reactive protein level (RESULTS: Overall, 100 of 225 patients (44.4%) had high baseline MRI inflammation. In patients with high baseline MRI inflammation, a significantly greater proportion achieved remission at 12 months with abatacept plus MTX versus MTX across SDAI (45.1% versus 16.3%; P = 0.0022), CDAI (47.1% versus 20.4%; P = 0.0065), and Boolean indices (39.2% versus 16.3%; P = 0.0156). In patients with low baseline MRI inflammation, remission rates were not significantly different with abatacept plus MTX versus MTX (SDAI: 39.7% versus 32.3%; P = 0.4961).CONCLUSION: In seropositive, MTX-naive patients with early RA and presence of objectively measured high inflammation by MRI, indicating poor prognosis, remission rates were higher with abatacept plus MTX treatment versus MTX.

RATIONALE AND OBJECTIVE: Low muscle mass relative to fat mass (relative sarcopenia) has been associated with mortality and disability but has not been examined following transplantation. We studied how measures of body composition change after receipt of a kidney allograft. STUDY DESIGN: Prospective longitudinal cohort study. SETTING AND PARTICIPANTS: 60 kidney transplant recipients (ages 20–60 years) at the University of Pennsylvania. EXPOSURE: Kidney transplantation. OUTCOMES: DXA measures of fat mass index (FMI) and appendicular lean mass index (ALMI; representing muscle mass), CT measures of muscle density (low density represents increased intramuscular adipose tissue), dynamometer measures of leg muscle strength, and physical activity. ALMI relative to FMI (ALM(FMI)) is an established index of relative sarcopenia. ANALYTICAL APPROACH: Measures expressed as age, sex, and race-specific Z-scores for transplant recipients were compared to 327 healthy controls. Regression models were used to identify correlates of change in outcome Z-scores and compare transplant recipients to controls. RESULTS: At transplantation, ALMI, ALMI(FMI), muscle strength and muscle density Z-scores were lower vs. controls (all p≤0.001). Transplant recipients received glucocorticoids throughout. The prevalence of obesity increased from 18 to 45%. Although ALMI increased following transplantation (p

OBJECTIVE: We aimed to determine whether NaF-PET/CT or FDG-PET/CT can detect abdominal aortic molecular calcification and inflammation in patients with rheumatoid arthritis (RA).METHODS: In this study, 18 RA patients (4 women, 14 men; mean age 56.0 ± 11.7) and 18 healthy controls (4 women, 14 men; mean age 55.8 ± 11.9) were included. The controls were matched to patients by sex and age (± 4 years). All subjects of this study underwent NaF-PET/CT scanning 90 min following the administration of NaF. FDG-PET/CT imaging was performed 180 min following intravenous FDG injection. Using OsiriX software, the global mean standardized uptake value (global SUVmean) in abdominal aorta was calculated for both FDG and NaF. The NaF SUVmean and FDG SUVmean were divided by the blood pool activity providing target-to-background ratios (TBR) namely, NaF-TBRmean and FDG-TBRmean. The CT calcium volume score was obtained using a growing region algorithm based on Hounsfield units.RESULTS: The average NaF-TBRmean score among RA patients was significantly greater than that of healthy controls (median 1.61; IQR 1.49-1.88 and median 1.40; IQR 1.23-1.52, P = 0.002). The average CT calcium volume score among RA patients was also significantly greater than that of healthy controls (median 1.96 cm3; IQR 0.57-5.48 and median 0.004 cm3; IQR 0.04-0.05, P CONCLUSION: Quantitative assessment with NaF-PET/CT identifies increased molecular calcification in the wall of the abdominal aorta among patients with RA as compared with healthy controls, while quantitative assessment with FDG-PET/CT did not identify a difference in aortic vessel wall FDG uptake between the RA and healthy control groups.

ObjectivesThe impact of immunosuppression on postoperative outcomes has primarily been studied in patients undergoing joint replacement surgery. We aimed to evaluate the impact of biologics and glucocorticoids on outcomes after other major surgeries.MethodsThis retrospective cohort study used Medicare data 2006–2015 to identified adults with rheumatoid arthritis undergoing hip fracture repair, abdominopelvic surgery (cholecystectomy, hysterectomy, hernia, appendectomy, colectomy) or cardiac surgery (coronary artery bypass graft, mitral/aortic valve). Logistic regression with propensity-score-based inverse probability weighting compared 90-day mortality and 30-day readmission in patients receiving methotrexate (without a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD)), a tumour necrosis factor inhibitor (TNFi) or a non-TNFi biologic/tsDMARD ResultsWe identified 10 777 eligible surgeries: 3585 hip fracture, 5025 abdominopelvic and 2167 cardiac surgeries. Compared with patients receiving methotrexate, there was no increase in the risk of 90-day mortality or 30-day readmission among patients receiving a TNFi (mortality adjusted OR (aOR) 0.83 (0.67 to 1.02), readmission aOR 0.86 (0.75 to 0.993)) or non-TNFi biologic/tsDMARD (mortality aOR 0.78 (0.49 to 1.22), readmission aOR 1.02 (0.78 to 1.33)). Analyses stratified by surgery category were similar. Risk of mortality and readmission was higher with 5–10 mg/day of glucocorticoids (mortality aOR 1.41 (1.08 to 1.82), readmission aOR 1.26 (1.05 to 1.52)) or >10 mg/day (mortality aOR 1.64 (1.02 to 2.64), readmission aOR 1.60 (1.15 to 2.24)) versus no glucocorticoids, although results varied when stratifying by surgery category.ConclusionsRecent biologic or tsDMARD use was not associated with a greater risk of mortality or readmission after hip fracture, abdominopelvic or cardiac surgery compared with methotrexate. Higher dose glucocorticoids were associated with greater risk.

INTRODUCTION/OBJECTIVES: Assess the impact of chronic lung diseases (CLD) on survival in rheumatoid arthritis (RA). METHOD: Among participants in the Veterans Affairs Rheumatoid Arthritis (VARA) Registry, a prospective cohort of U.S. Veterans with RA, we identified CLD and cardiovascular disease (CVD) using administrative and registry data. Demographics, smoking status, RA characteristics including Disease Activity Score in 28 joints (DAS28), and disease-modifying anti-rheumatic drug (DMARD) use were obtained from registry data, which was linked to the National Death Index to obtain vital status. We evaluated associations of CLD with survival using multivariable Cox regression models. RESULTS: Among a large (n=2,053), male predominant (91%) RA cohort, 554 (27%) had CLD at enrollment. Mortality risk was increased 1.51-fold (95% CI 1.26–1.81) in RA patients with CLD after multivariable adjustment, a risk that was similar to that observed with CVD (HR CLD alone 1.46 [1.03–2.06]; CVD alone 1.62 [1.35–1.94]). Survival was significantly reduced in those with interstitial lung disease (ILD) as well as other forms of CLD. Mortality risk with methotrexate and biologic use was not different in those with CLD compared to those without (p interaction ≥ 0.15) using multiple exposure definitions and propensity score adjustment. CONCLUSIONS: Mortality risk is significantly increased in RA patients with CLD. This risk is attributable not only to ILD but also to other chronic lung conditions and does not appear to be substantially greater in those receiving methotrexate or biologic therapies. Comorbid lung disease should be targeted as a means of improving long-term outcomes in RA.