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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.

Although tumor necrosis factor inhibitors (TNFi) have favorably altered the treatment landscape for patients with axial spondyloarthritis (axSpA), there is limited data regarding TNFi persistence and reasons for discontinuation. This is an observational time-to-event study utilizing data collected for a prospective multiple-disease registry of US Veterans with axSpA treated with TNFi therapies and recruited over a 10 year period. Clinical, serological, and comorbid parameters were collected. Corporate Data Warehouse Pharmacy files provided courses of the 5 TNFi agents, and response to treatment was documented. Individual TNFi persistence was established utilizing univariate and multivariate Cox proportional models, and reasons for discontinuation were obtained by physician chart review. Two-hundred and fifty-five axSpA patients received 731 TNFi courses. A majority of patients (84.3%) had TNFi persistence at 12 months; 63.5% and 47.1% at 24 and 36 months, respectively. Compared to adalimumab, infliximab demonstrated greater persistence, certolizumab the least. Age, smoking status, BMI, comorbidity burden, inflammatory markers and HLA-B27 did not predict TNFi persistence or discontinuation. Stroke and peripheral arterial disease increased the probability of TNFi discontinuation. Secondary non-response (SNR) was the most common reason for discontinuation (46% of all courses); non-adherence (6%) and clinical remission (2%) were uncommon. Pain score at enrollment, myocardial infarction, African American race and inflammatory bowel disease (IBD) predicted TNFi response. While initial persistence of TNFi treatment was high, a large proportion of the patients discontinued initial TNFi therapy by 3 years, primarily due to loss of efficacy. While further research identifying potential predictors of TNFi discontinuation in axSpA is warranted, access to alternate disease-modifying therapies is needed.

OBJECTIVE Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. This study was undertaken to examine the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA). METHODS We conducted an active comparator safety study of HCQ in a propensity score-matched cohort of 8,852 US veterans newly diagnosed as having RA between October 1, 2001 and December 31, 2017. Patients were started on HCQ (n = 4,426) or another nonbiologic disease-modifying antirheumatic drug (DMARD; n = 4,426) after RA diagnosis, up to December 31, 2018, and followed up for 12 months after therapy initiation, up to December 31, 2019. RESULTS Patients had a mean ± SD age of 64 ± 12 years, 14% were women, and 28% were African American. The treatment groups were balanced with regard to 87 baseline characteristics. There were 3 long QT syndrome events (0.03%), 2 of which occurred in patients receiving HCQ. Of the 56 arrhythmia-related hospitalizations (0.63%), 30 occurred in patients in the HCQ group (hazard ratio [HR] associated with HCQ 1.16 [95% confidence interval (95% CI) 0.68-1.95]). All-cause mortality occurred in 144 (3.25%) and 136 (3.07%) of the patients in the HCQ and non-HCQ groups, respectively (HR associated with HCQ 1.06 [95% CI, 0.84-1.34]). During the first 30 days of follow-up, there were no long QT syndrome events, 2 arrhythmia-related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group). CONCLUSION Our findings indicate that the incidence of long QT syndrome and arrhythmia-related hospitalization is low in patients with RA during the first year after the initiation of HCQ or another nonbiologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death.

Recent evidence suggest that hydroxychloroquine use is not associated with higher one-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study.We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8852 Veterans (mean age, 64±12 years, 14% women, 28% African Americans) with newly-diagnosed RA, in which 4426 patients initiated on hydroxychloroquine and 4426 initiated on another non-biologic disease-modifying antirheumatic drug (DMARD) were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019.Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in hydroxychloroquine and other DMARD groups, respectively, during first two years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS in hydroxychloroquine group (number needed to harm, 403; 95% CI, 217-1740) and 181% greater relative risk (95% CI, 11%-613%; p=0.030). Although overall 10-year risk remained significant (hazard ratio, 2.17; 95% CI, 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and one over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality.Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter which became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

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.

This study was conducted to assess the utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting radiographic sacroiliitis and active disease in axial spondyloarthritis (SpA) and to explore the association between use of a tumor necrosis factor inhibitor (TNFi) and these laboratory values compared with traditional inflammatory markers.Observational data from the Program to Understand the Longterm Outcomes in Spondyloarthritis (PULSAR) registry were analyzed. We generated receiver operating characteristic curves to calculate laboratory cutoff values; we used these values in multivariable logistic regression models to identify associations with radiographically confirmed sacroiliitis and active disease. We also used logistic regression to determine the likelihood of elevated laboratory values after initiation of TNFi.Most study participants (n = 354) were White, male, and HLA-B27 positive. NLR (odds ratio [OR] 1.459, P = 0.034), PLR (OR 4.842, P 0.001), erythrocyte sedimentation rate (OR 4.397, P 0.001), and C-reactive protein (CRP) level (OR 2.911, P = 0.001) were independent predictors of radiographic sacroiliitis. Models that included PLR with traditional biomarkers performed better than those with traditional biomarkers alone. NLR (OR 6.931, P = 0.002) and CRP (OR 2.678, P = 0.004) were predictors of active disease, but the model that included both NLR and CRP performed better than CRP alone. TNFi use reduced the odds of elevated NLR (OR 0.172, P 0.001), PLR (OR 0.073, P 0.001), erythrocyte sedimentation rate (OR 0.319, P 0.001), and CRP (OR 0.407, P 0.001), but models that included NLR or PLR and traditional biomarkers performed best.These findings demonstrate an association between NLR and PLR and sacroiliitis and disease activity, with NLR and PLR showing response after TNFi treatment and adding useful clinical information to established biomarkers, thus perhaps assisting in management of axial SpA.

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.

A key issue in the response to the coronavirus disease 2019 (COVID‐19) pandemic is the internationally recognised observation that COVID‐19 disproportionally affects the Black and Minority Ethnic Population (BAME) (1). We focus predominantly on the countries of the UK, USA, and India COVID‐19 rheumatology challenges and examples. This unprecedented public health crisis started in China in Dec 2019, following an infection caused by a novel coronavirus strain, named as SARS‐CoV2 (2). The World Health Organisation in March 2020 declared this public health emergency as a pandemic (2). COVID‐19 pandemic has moved from country to country peaking at different times despite implementation of strict preventive measures, including complete lock down periods with varied success. Case fatality and mortality rates have been highly variable across nations as well as different ethnic groups (3).

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 Interstitial lung disease (ILD) is a frequent complication of rheumatoid arthritis (RA), occurring in up to 40% of patients during the course of their disease. Early diagnosis is critical, particularly given the shared clinicoepidemiologic features between advanced rheumatoid arthritis-associated ILD (RA-ILD) and idiopathic pulmonary fibrosis (IPF). This study was undertaken to define the molecular basis of this overlap through comparative profiling of serum proteins in RA-ILD and IPF. Methods Multiplex enzyme-linked immunosorbent assays (ELISAs) were used to profile 45 protein biomarkers encompassing cytokines/chemokines, growth factors, and matrix metalloproteinases (MMPs) in sera obtained from RA patients with ILD and those without, individuals with IPF, and healthy controls. Levels of selected serum proteins were compared between patient subgroups using adjusted linear regression, principal component analysis (PCA), and least absolute shrinkage and selection operator (LASSO) modeling. Results Multiplex ELISA-based assessment of sera from 2 independent cohorts (Veterans Affairs [VA] and Non-VA) revealed a number of non-overlapping biomarkers distinguishing RA-ILD from RA without ILD (RA-no ILD) in adjusted regression models. Parallel analysis of sera from IPF patients also yielded a discriminatory panel of protein markers in models adjusted for age/sex/smoking, which showed differential overlap with profiles linked to RA-ILD in the VA cohort versus the Non-VA cohort. PCA revealed several distinct functional groups of RA-ILD-associated markers that, in the VA cohort, encompassed proinflammatory cytokines/chemokines as well as 2 different subsets of MMPs. Finally, LASSO regression modeling in the Non-VA and VA cohorts revealed distinct biomarker combinations capable of discriminating RA-ILD from RA-no ILD. Conclusion Comparative serum protein biomarker profiling represents a viable method for distinguishing RA-ILD from RA-no ILD and identifying population-specific mediators shared with IPF.

Although tumor necrosis factor inhibitors (TNFi) have favorably altered the treatment landscape for patients with axial spondyloarthritis (axSpA), there is limited data regarding TNFi persistence and reasons for discontinuation. This is an observational time-to-event study utilizing data collected for a prospective multiple-disease registry of US Veterans with axSpA treated with TNFi therapies and recruited over a 10 year period. Clinical, serological, and comorbid parameters were collected. Corporate Data Warehouse Pharmacy files provided courses of the 5 TNFi agents, and response to treatment was documented. Individual TNFi persistence was established utilizing univariate and multivariate Cox proportional models, and reasons for discontinuation were obtained by physician chart review. Two-hundred and fifty-five axSpA patients received 731 TNFi courses. A majority of patients (84.3%) had TNFi persistence at 12 months; 63.5% and 47.1% at 24 and 36 months, respectively. Compared to adalimumab, infliximab demonstrated greater persistence, certolizumab the least. Age, smoking status, BMI, comorbidity burden, inflammatory markers and HLA-B27 did not predict TNFi persistence or discontinuation. Stroke and peripheral arterial disease increased the probability of TNFi discontinuation. Secondary non-response (SNR) was the most common reason for discontinuation (46% of all courses); non-adherence (6%) and clinical remission (2%) were uncommon. Pain score at enrollment, myocardial infarction, African American race and inflammatory bowel disease (IBD) predicted TNFi response. While initial persistence of TNFi treatment was high, a large proportion of the patients discontinued initial TNFi therapy by 3 years, primarily due to loss of efficacy. While further research identifying potential predictors of TNFi discontinuation in axSpA is warranted, access to alternate disease-modifying therapies is needed.

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.

To evaluate the utility of a web-based advocacy training tool in increasing advocacy awareness.Early career rheumatologists who attended 2019 American College of Rheumatology Advocacy 101 were invited to participate. A web-based tool consisting of 9 cases covering various aspects of advocacy was developed and included the opportunity for continuing medical education credit. A preparticipation questionnaire surveyed prior involvement, knowledge, and willingness to participate in an advocacy program. Participants rated cases based on educational quality, relevance of content, achievement of training goals, competency, and evidence of bias. Two web-based conferences were held to address technical questions, review, and discussion of cases and responses, and to obtain feedback.Twenty-one early career rheumatologists from 9 academic institutions enrolled, with 15 (75%) completing all cases. Correct continuing medical education answers were scored on 85% of cases. Overall educational quality of content received a mean rating of 4.3 of 5. Seven cases achieved positive ratings for relevance of case content, achievement of training goals, objectivity, and competency. All cases were assessed free of bias. Feedback indicated that 30 minutes were dedicated to each case, and that a combination of skill set and content learning were most effective. Pre- and postquestionnaire scores indicated significant improvement in knowledge of advocacy matters (P 0.0001).A web-based advocacy training tool was successful in significantly improving awareness and knowledge of advocacy matters among early career rheumatologists. This innovative educational tool may play a vital role in shaping the future of rheumatology for both patients and physicians.

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.

Background: While the Psoriasis Area and Severity Index (PASI) represents the most commonly used assessment tool for psoriasis severity, it has been criticized for its complexity in clinical practice. Objective: To validate a simplified 2-item patient-administered limited measure psoriasis area and severity score (PALMPASS) compared to standardized measure of psoriasis. Materials and Methods: This was a prospective observational survey of adult patients with psoriasis and psoriatic arthritis in Veterans Affairs Medical Center (VAMC) dermatology and rheumatology clinics participating in the Program to Understand the Longterm outcomes in SpondyloARthritis registry between January and June 2016 (n = 885). Patients at 7 US VAMCs (n = 363) completed a 2-item, 11-point PALMPASS questionnaire, assessing (1) how psoriasis affected the patient and (2) the degree of surface area involvement. Results from the PALMPASS were then compared to the PASI, the Psoriasis Symptom Inventory (PSI) and the Dermatology Life Quality Index (DLQI). Data were analyzed using Lin concordance, intraclass correlations, Spearman correlations, and linear regression. Results: Strong correlations existed between PALMPASS and PASI (Spearman ρ = 0.74, P < .001), PSI (Spearman ρ = 0.71, P = .001), and DLQI (Spearman ρ = 0.77, P < .001). Results were comparable in analyses based on intraclass correlations. Elevated C-reactive protein concentrations correlated with higher PALMPASS. Conclusion: The PALMPASS is a patient-reported instrument that demonstrates validity and serves as a reliable and simplified tool to guide evidence-based management.

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

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.

Background:Rheumatoid Arthritis (RA) is associated with an increased risk of cardiovascular disease. RA is also associated with increased risk of chronic kidney disease (CKD) (1, 2), which is a known cardiovascular risk factor (3). We hypothesized that RA (compared with no RA) would be associated with increased risk of mortality among a cohort of patients with CKD.Objectives:To determine the risk of mortality in RA patients with CKD.Methods:This study was conducted using participants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) prospective Chronic Renal Insufficiency Cohort (CRIC) study. Approximately 3600 participants were enrolled from seven US clinical centers. Patients aged 21 – 74 years with mild to moderate CKD were eligible for enrollment. The primary outcome of interest was all-cause mortality. Secondary outcomes of interest included: kidney event defined as end stage renal disease (ESRD) or 50% decline in estimated glomerular filtration rate (eGFR), myocardial infarction (MI), cerebrovascular accident (CVA), heart failure and a composite cardiovascular endpoint. The association of RA mortality over time was examined using Cox multivariate proportional hazards regression, adjusting for potential covariates (age, sex, race/ethnicity, BMI, current smoker, education).Results:The study cohort included 492 participants with self-reported RA with a mean follow up of 9.5 years. Compared to the non-RA group, RA patients tended to be older, female, Black. Hypertension, diabetes, use of prednisone was more prevalent among the RA cohort. The unadjusted hazards ratio (HR) for mortality based on RA status was 1.45 (1.26, 1.67) but this association was attenuated after adjusting for the confounding factors [aHR 1.09 (0.94, 1.27)] (Table 1). Participants with RA had a significantly higher risk for heart failure than those without RA [aHR 1.17 (1.02, 1.34)]. We did not observe a statistically significant association between RA status and other secondary outcomes.Conclusion:RA was not associated with higher mortality among participants with CKD. However, RA was associated with higher rates of heart failure. Further studies evaluating the mechanisms behind this association are needed.References:[1]Kochi M, Kohagura K, Shiohira Y, Iseki K, Ohya Y. Chronic kidney disease, inflammation, and cardiovascular disease risk in rheumatoid arthritis. J Cardiol. 2018;71(3):277-83.[2]Sumida K, Molnar MZ, Potukuchi PK, Hassan F, Thomas F, Yamagata K, et al. Treatment of rheumatoid arthritis with biologic agents lowers the risk of incident chronic kidney disease. Kidney Int. 2018;93(5):1207-16.[3]Chiu HY, Huang HL, Li CH, Chen HA, Yeh CL, Chiu SH, et al. Increased Risk of Chronic Kidney Disease in Rheumatoid Arthritis Associated with Cardiovascular Complications - A National Population-Based Cohort Study. PLoS One. 2015;10(9):e0136508.[4]Muthukumar P, Dhanapriya J, Gopalakrishnan N, Dineshkumar T, Sakthirajan R, Balasubramaniyan T. Evaluation of renal lesions and clinicopathologic correlation in rheumatoid arthritis. Saudi J Kidney Dis Transpl. 2017;28(1):44-50.Table 1.Estimated hazard ratios (HR) for various outcomes from Cox proportional hazards regression for RA statusUnadjustedModel 1Model 2HR (95% CI)HR (95% CI)HR (95% CI)Death1.45 (1.26, 1.67)1.09 (0.94, 1.27)1.13 (0.97, 1.32)MI or death1.43 (1.25, 1.63)1.09 (0.95, 1.26)1.15 (0.99, 1.33)CVA or death1.42 (1.24, 1.63)1.07 (0.92, 1.24)1.11 (0.95, 1.29)CHF or death1.54 (1.35, 1.75)1.17 (1.02, 1.34)1.22 (1.06, 1.40)Composite1.49 (1.31, 1.69)1.13 (0.99, 1.30)1.18 (1.03, 1.35)Kidney event1.09 (0.94, 1.27)0.91 (0.78, 1.07)1.01 (0.85, 1.20)Model 1 adjusted for: age, sex, race/ethnicity, BMI, current smoker, educationModel 2 adjusted for: model 1 + cardiovascular risk factors (urine albumin creatinine ratio, systolic blood pressure, estimated glomerular filtration rate)Disclosure of Interests:None declared

To evaluate the relationship between air pollutant (AP) exposure and rheumatoid arthritis (RA) autoantibody status We performed a cross sectional study utilizing enrollment data from participants in the Veterans Affairs rheumatoid arthritis registry. HLA-DRB1 shared epitope (SE), smoking, rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (ACPA) status were collected. Mean exposure levels were obtained for AP (NO2, SO2, particulate matter [PM2.5, PM10], and ozone) from air quality monitoring stations at patients’ residential zip codes in the year prior to enrollment. Multivariable logistic and ordinary least squares regression models were used to determine independent associations of AP with RA seropositivity and autoantibody concentration. The cohort included 557 veterans (90% male, 76% Caucasian), with mean age of 70 years and mean disease duration of 13 years. The majority were HLA-DRB1 SE, RF, and ACPA positive (73%, 79%, and 76%, respectively). In univariate models, PM2.5 exposure was associated with higher ACPA concentration (p = 0.009). Similarly, in multivariable regression models, PM2.5 exposure was independently associated with higher ACPA concentration (p = 0.037). Current smoking independently predicted RF and ACPA positivity and titers, while HLA-DRB1 SE alleles were associated with RF positivity and ACPA positivity and titers. In an elderly cohort of RA patients, fine particulate matter (PM2.5) exposure independently predicted higher ACPA concentration. Further study of fine particulate matter in the pathogenesis of RA is warranted.

Background The Veterans Affairs (VA) Rheumatoid Arthritis (RA) (VARA) registry is an observational cohort study of US Veterans with RA at 11 VA Medical Centers. VARA investigators capture clinical and laboratory disease activity measures (DAMs) during clinic visits via standardized templates in the electronic health record (EHR). Six clinical (tender/swollen joints, patient/provider global, MD-HAQ, pain) and 2 laboratory (ESR, CRP) DAMs are extracted post-visit using natural language processing (NLP). Objectives This analysis determined the impact of an audit, feedback and data correction system on the quantity and quality of DAMs collected in the VARA registry. Methods After September 2017, VARA site investigators were provided monthly feedback reports of incomplete/missing DAMs for the prior month to allow sites to correct data entry errors. Updated and/or corrected data were entered into the EHR via note addendums and then automatically re-extracted by NLP to complete the capture of DAM data. DAMs from October 1, 2016 to September 30, 2017 (pre-feedback implementation – Pre-IMP) was compared to October 1, 2017 to September 30, 2018 (post-feedback implementation – Post-IMP). Results During the pre-IMP period, there were 2,411 notes with DAMs collected on 1,116 unique patients compared to 2,873 notes on 1,208 unique patients in the post-IMP period - an increase of 92 (8.2%) unique patients and 460 (19.1%) notes. Enrollment in the VARA registry only increased by 121 (6.5%) during post-IMP period. During post-IMP period, there were 541 notes identified with deficiencies in clinical DAMs and monthly audit and feedback reports were provided to VARA sites to allow corrections. Individual site review resulted in 376 additional DAMs in 225 notes, with complete resolution of all error in 137 (25.3%) notes. The quantity of DAMs collected increased from 15,709 to 21,064, a 34.1% increase with the average number of DAMs collected per note rising from 4.9 to 5.6. The quality of data improved as demonstrated by the proportion of notes with all 6 clinical DAMs increasing from 52.5% to 81.1% and other improvements in quality/completeness as noted in table. Conclusion An audit, feedback, and efficient data collection system improved both the quantity and quality of DAMs collected. The improvement in the collection of DAMs in RA patients will further enhance epidemiologic and outcomes studies of RA and provide higher quality longitudinal data to enhance the care of RA patients. References [1] Fed Pract 2015; 32(5):24-29 Acknowledgement Work Support in Part by VA HSR&D and VA Specialty Care Centers of Innovation Disclosure of Interests Grant Cannon Grant/research support from: Amgen Inc., Jorge Rojas: None declared, Neill Bell: None declared, Namrata Singh: None declared, Ted Mikuls: None declared, Liron Caplan: None declared, Gail Kerr: None declared, Joshua Baker: None declared, Angelo Gaffo: None declared, Jennifer Barton: None declared, Deana Lazaro: None declared, J Steuart Richards: None declared, Brian Sauer Grant/research support from: Amgen Inc.

Objective To examine the potential of circulating cytokines and chemokines as biomarkers of cancer mortality risk in patients with rheumatoid arthritis (RA). Methods Male participants in the Veterans Affairs RA registry were followed up from the time of enrollment until death or December 2013. Cytokines and chemokines were measured in banked serum obtained at the time of enrollment, using a bead-based multiplex assay, and a previously developed cytokine score was calculated. Vital status and cause of death were determined through the National Death Index. Associations of cytokines with cancer mortality were examined using multivariable competing-risks regression. Results Among 1,190 men with RA, 60 cancer deaths (30 of which were attributable to lung cancer) occurred over 5,307 patient-years of follow-up. The patients had a mean age of 64.5 years, had established disease (median duration 8.7 years), were seropositive for rheumatoid factor (81%) or anti–cyclic citrullinated peptide antibody (77%), and frequently had a history of smoking (82% current or former). Seven of 17 analytes examined were individually associated with cancer mortality. The cytokine score was associated with overall cancer (subhazard ratio [SHR] 1.42, 95% confidence interval [95% CI] 1.08–1.85) and lung cancer (SHR 1.86, 95% CI 1.57–2.19) mortality in multivariable analyses. Those in the highest quartile of cytokine scores had a >2-fold increased risk of overall cancer mortality (P = 0.039) and a 6-fold increased risk of lung cancer mortality (P = 0.028) relative to the lowest quartile. A synergistic interaction between current smoking and high cytokine score was observed. Conclusion Serum cytokines and chemokines are associated with cancer and lung cancer mortality in men with RA, independent of multiple factors including age, smoking status, and prevalent cancer.

Author(s): de Lautour, Hugh; Taylor, William J; Adebajo, Ade; Alten, Rieke; Burgos-Vargas, Ruben; Chapman, Peter; Cimmino, Marco A; da Rocha Castelar Pinheiro, Geraldo; Day, Ric; Harrold, Leslie R; Helliwell, Philip; Janssen, Matthijs; Kerr, Gail; Kavanaugh, Arthur; Khanna, Dinesh; Khanna, Puja P; Lin, Chingtsai; Louthrenoo, Worawit; McCarthy, Geraldine; Vazquez-Mellado, Janitzia; Mikuls, Ted R; Neogi, Tuhina; Ogdie, Alexis; Perez-Ruiz, Fernando; Schlesinger, Naomi; Ralph Schumacher, H; Scire, Carlo A; Singh, Jasvinder A; Sivera, Francisca; Slot, Ole; Stamp, Lisa K; Tausche, Anne-Kathrin; Terkeltaub, Robert; Uhlig, Till; van de Laar, Mart; White, Douglas; Yamanaka, Hisashi; Zeng, Xuejun; Dalbeth, Nicola | Abstract: To establish consensus for potential remission criteria to use in clinical trials of gout.Experts (n = 88) in gout from multiple countries were invited to participate in a web-based questionnaire study. Three rounds of Delphi consensus exercises were conducted using SurveyMonkey, followed by a discrete-choice experiment using 1000Minds software. The exercises focused on identifying domains, definitions for each domain, and the timeframe over which remission should be defined.There were 49 respondents (56% response) to the initial survey, with subsequent response rates ranging from 57% to 90%. Consensus was reached for the inclusion of serum urate (98% agreement), flares (96%), tophi (92%), pain (83%), and patient global assessment of disease activity (93%) as measurement domains in remission criteria. Consensus was also reached for domain definitions, including serum urate (l0.36 mm), pain (l2 on a 10-point scale), and patient global assessment (l2 on a 10-point scale), all of which should be measured at least twice over a set time interval. Consensus was not achieved in the Delphi exercise for the timeframe for remission, with equal responses for 6 months (51%) and 1 year (49%). In the discrete-choice experiment, there was a preference towards 12 months as a timeframe for remission.These consensus exercises have identified domains and provisional definitions for gout remission criteria. Based on the results of these exercises, preliminary remission criteria are proposed with domains of serum urate, acute flares, tophus, pain, and patient global assessment. These preliminary criteria now require testing in clinical data sets.

Objective There has been limited investigation into cause-specific mortality and the associated risk factors in men with rheumatoid arthritis (RA). We investigated all-cause and cause-specific mortality in men with RA, examining determinants of survival. Methods Men from a longitudinal RA registry were followed from enrollment until death or through 2013. Vital status and cause of death were determined using the National Death Index. Crude mortality rates and standardized mortality ratios (SMRs) were calculated for all-cause, cardiovascular disease (CVD), cancer, and respiratory mortality. Associations with all-cause and cause-specific mortality were examined using multivariable Cox proportional hazards and competing-risks regression. Results There were 1,652 men with RA and 332 deaths. The leading causes of death were CVD (31.6%; SMR 1.77 [95% confidence interval (95% CI) 1.46–2.14]), cancer (22.9%; SMR 1.50 [95% CI 1.20–1.89]), and respiratory disease (15.1%; SMR 2.90 [95% CI 2.20–3.83]). Factors associated with all-cause mortality included older age, white race, smoking, low body weight, comorbidity, disease activity, and prednisone use. Rheumatoid factor concentration and nodules were associated with CVD mortality. There were no associations of methotrexate or biologic agent use with all-cause or cause-specific mortality. Conclusion Men in this RA cohort experienced increased all-cause and cause-specific mortality, with a 3-fold risk of respiratory-related deaths compared to age-matched men in the general population. Further studies are needed in order to examine whether interventions targeting potentially modifiable correlates of mortality might lead to improved long-term survival in men with RA.

Objective.To evaluate associations of HLA-DRB1 haplotypes and shared epitope (SE) with rheumatoid arthritis (RA) severity and all-cause mortality in RA.Methods.Patients with RA from the Veterans Affairs Rheumatoid Arthritis (VARA) registry were followed from enrollment until death or December 31, 2013. Clinical characteristics, DNA, and serum were collected at enrollment. Radiographic damage, the presence or absence of subcutaneous nodules, disease activity measures, and functional status were assessed at enrollment and updated during followup. Sixteen HLA-DRB1 haplotypes and SE status were determined from banked DNA. Associations between HLA-DRB1 haplotypes, RA disease characteristics, and mortality were assessed in multivariable regression models.Results.Within VARA, 1443 participants had genotyping and accrued 6150 patient-years of followup. Haplotypes VKA, VRA, LRA, SRA, SRE, SKR, and SEA, and SE alleles were significantly associated with seropositivity for rheumatoid factor (RF) and/or anticyclic citrullinated peptide (anti-CCP). Haplotypes VKA and SKR were associated with higher RF concentrations, while VRA, DRE, and GRQ were associated with lower RF concentrations. Haplotypes VKA, VRA, and LRA were associated with higher concentrations of anti-CCP antibody, while haplotypes SRA, SRE, LEA, SKR, and SEA were significantly associated with lower anti-CCP concentrations. Haplotype VKA (OR 1.39, 95% CI 1.08–1.80) was associated with increased frequency of radiographic damage at enrollment but none of the haplotypes were associated with the presence of subcutaneous nodules. Haplotypes SKA (HR 1.52, 95% CI 1.26–1.83) was associated with higher mortality.Conclusion.HLA-DRB1 haplotypes are independently and variably associated with seropositivity, autoantibody concentrations, and outcomes in RA.

To assess the potential utility of a cytokine measurement in rheumatoid arthritis (RA) patients with active joint disease but normal acute phase reactants (APR). RA patients in a longitudinal observational registry with available cytokine array data were included. Patients were categorized based on agreement/disagreement of physical examination and APR measurements: concordant high (CH) [high tender and/or swollen joint counts (TJC + SJC > 3) and APR (ESR ≥ 28 mm/h + CRP ≥ 1.5 mg/L)]; concordant low (CL) [TJC + SJC ≤ 3 and normal APR]. Discordant (D) [TJC + SJC > 3 and normal APR] patients were stratified into low, medium, and high-disease activity (DL, DM, DH). Weighted-average and log-transformed cytokine scores were calculated based on results of a cytokine array. Chi-square tests compared categorical variables by concordance status; t tests, Wilcoxon rank-sum tests, ANOVA models, and ordinary least squares (OLS) regressions were used to compare continuous measures. RA patients (n = 1467) were predominantly male (91%). Compared to CH patients (n = 174), D (n = 434) were younger, less frequently seropositive, with lower TJC, SJC, and DAS28-3v scores (p

Background The expanded therapeutic modalities in rheumatoid arthritis (RA) provide options to achieve low disease activity or remission. Yet, in routine care, the frequency and choice of switching of biologic DMARD (bDMARD) amongst ethnic subsets when there is inefficacy, is unknown. Objectives To evaluate frequency and choice of biologic switch in ethnic RA subsets Methods Patients enrolled in the Ethnic Minority RA Consortium (EMRAC), with at least one followup visit were analysed. Data included clinical outcomes as assessed by RAPID3 tender/swollen joint counts; medication use (prednisone, methotrexate, other DMARD), and bDMARD (Tumour Necrosis factor inhibitors (TNFi) and non-TNFi). Minimally clinical improvement (MCI) in RAPID3 was defined as a decrease of ≥3.2 points during followup. Differences between medication usage, biologic switch, and RAPID3 improvement between race and ethnicity groups while on biologics, was investigated. Results 1040 subjects with 3719 follow-up visits spanning an average of 63.2 weeks were analysed. African Americans and Hispanics comprised 24% and 15%, respectively. Compared to Whites, African Americans and Hispanics had significantly less education (p Switching between TNFi and non-TNFi was recorded in only 9 subjects, with 7 subjects switching from TNFi to non-TNFi. There was no statistical difference between race/ethnic groups in frequency of bDMARD switching, nor within bDMARD class (TNFi class, p=cc; non-TNFi class, p=bb). bDMARD treatment led to MCI in RAPID3 in 101 (38%) subjects and in more African Americans (29 [48%]) and Hispanics (12 [41%]) than in Whites (49 [37%]) (but not statistically significant). Conclusions In our cohort, disparity was seen in bDMARD use between race and ethnic groups but had similar and infrequent biologic switch. Based upon these data, efforts to eliminate biologic use disparity remains paramount and supersedes concerns regarding disparity in biologic switching. Disclosure of Interest G. Kerr Grant/research support from: BMS, Genentech, Pfizer, C. Swearingen Grant/research support from: BMS, Genentech, Pfizer, S. Hochberg: None declared, J. Ude: None declared, Y. Yazici Grant/research support from: BMS, Genentech, Pfizer

Background Hyperuricemia is common and along with comorbidities, is increasing in prevalence. Though often asymptomatic and hence, under diagnosed, it may be associated with subclinical urate deposition. Ultrasound (US) imaging can detect urate deposition in individuals with asymptomatic hyperuricemia (ASU). Objectives To evaluate the association of comorbidities with urate deposition via US in ASU. Methods ASU was defined as serum urate (sUA) >6 mg/dl; sUA Results Of 95 predominantly non-Hispanic Blacks (mean age 59.7 years, BMI ~32 kg/m2), ASU subjects (n=71, median sUA=8.0) were older men, with more frequent HTN, CVD, CKD, alcohol ingestion versus controls. In multivariate analyses adjusting for demographic characteristics, BMI, CKD, and alcohol use were positively associated with sUA >6 mg/dl; while HTN, CVD, and CKD were positively associated with sUA >8 mg/dl. Adjusting for comorbidities, sUA >8 mg/dl was significantly associated with urate deposition at knee (OR=3.20; p=0.03), quadriceps and Achilles tendons (OR=4.14; p 6 mg/dl alone, however, did not predict urate deposition. Conclusions Presence of HTN, CVD and CKD are associated with higher levels of sUA and increases the risk of urate deposition in ASU patients. Identifying a subset of ASU patients that may benefit from urate lowering therapy requires further stratification and long term follow up for incident gouty arthritis in order to alter current urate lowering treatment guidelines. Disclosure of Interest G. Kerr Grant/research support from: Ardea, Grunenthal, Horizon, S. Dowell Grant/research support from: Horizon, A. Wells: None declared, R. Haddad: None declared, P. DeMarco: None declared, J. Joseph: None declared, J. Ude: None declared, S. Hochberg: None declared, J. Huang: None declared, D. Nashel: None declared

Objective To assess disease characteristics, disease activity, and treatment patterns in rheumatoid arthritis (RA) patients with comorbid hepatitis C virus (HCV) infection. Methods RA patients with concomitant HCV were identified within the Veterans Affairs Rheumatoid Arthritis Registry. HCV was defined as at least 1 diagnostic code present in medical record databases. Generalized estimating equations in linear regression models compared component and composite measures of disease activity between HCV-positive and HCV-negative patients over the study period, accounting for within-subject correlations. Similar analysis of pharmacy databases evaluated medication use within each group. Results Ninety-two of 1,706 registry participants (5.1%) were identified with concomitant HCV. At enrollment, HCV-positive patients were younger (mean ± SD 61.7 ± 7.1 years versus 67.5 ± 11.2 years; P < 0.001), more often African American (35% versus 15%; P < 0.001), and smokers (48% versus 26%; P < 0.001). In unadjusted and adjusted analyses incorporating all study visits, patient-reported outcomes (pain, tender joints, and patient global scores) were higher in HCV-positive patients, contributing to higher disease activity scores. There was no difference in physician-reported outcomes (swollen joints or physician global scores). HCV-positive patients had lower C-reactive protein levels (β −0.30 [95% confidence interval (95% CI) −0.53, −0.07], P = 0.01). Over all visits, HCV-positive patients were less likely to receive methotrexate (odds ratio [OR] 0.27 [95% CI 0.17, 0.40], P < 0.001), and more likely to receive prednisone (OR 1.41 [95% CI 1.02, 1.97], P = 0.04) and anti–tumor necrosis factor α (anti-TNFα) therapies (OR 1.51 [95% CI 1.04, 2.19], P = 0.03). Conclusion RA patients with concomitant HCV have higher disease activity scores, driven primarily by higher patient-reported measures. HCV-positive patients were more likely to be treated with prednisone and anti-TNFα therapies and less likely to receive methotrexate compared to HCV-negative patients.

This study examines: 1) alveolar bone loss (ABL), a hallmark of periodontitis, in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) patients versus control patients with osteoarthritis (OA); and 2) the association of ABL with RA disease activity and ACPA concentrations, including multiple antigen-specific ACPA.This multicenter case-control study includes 617 patients diagnosed with RA (n = 287) or OA (n = 330). Panoramic radiographs were taken; patients were categorized into low, moderate, or high tertiles based on mean percentage ABL. Serum ACPA was measured using second-generation anticyclic citrullinated peptide enzyme-linked immunosorbent assay and a multiplex platform to assess distinct antigen-specific ACPA. A generalized linear mixed model for binary data was used to compare stratified ABL in RA versus OA patients. Associations of moderate and high ABL (versus low) with RA disease activity and severity measures were examined using multivariate regression. Antigen-specific ACPA responses were compared among ABL tertiles using significance analysis of microarrays.ACPA-positive patients with RA had a significantly higher mean percentage of sites with ABL20% compared with patients with OA (P = 0.03). After multivariate adjustment, greater ABL was significantly associated with higher serum ACPA concentration (P = 0.004), 28-joint Disease Activity Score (P = 0.023), health assessment questionnaire disability (P = 0.05), tender joint count (P = 0.02) and joint space narrowing scores (P = 0.05) among patients with RA. ACPAs targeting citrullinated vimentin and histone were significantly higher in moderate and high ABL groups versus low, regardless of smoking status (q0.1%).Greater ABL was associated with higher ACPA, consistent with findings at articular sites. ACPA targeting could provide novel insight into important linkages between RA and periodontitis.

Objective To evaluate physician adherence with gout quality indicators (QIs) for medication use and monitoring, and behavioral modification (BM). Methods Gout patients were assessed for the QIs as follows: QI 1: initial allopurinol dosage

Background Comorbidity is common in ethnic patients with rheumatoid arthritis (RA) and often impact choice of DMARD therapy and clinical outcomes. In addition to simple summation of comorbidities, composite indices have been proffered as better predictors of poor clinical outcomes in patients with rheumatoid arthritis1. However, their applicability in ethnic RA subsets is unknown. Objectives To compare composite to mean comorbidity indices in ethnic subsets with rheumatoid arthritis. Methods Patients enrolled in the Ethnic Minority RA Consortium (EMRAC), with at least 6 months of followup data were analyzed. At enrollment, sociodemographic data and RA disease status, rheumatic disease comorbidity index (RCDI)1 and comorbidity count (COUNT)1 were analyzed amongst ethnic subsets. Spearman correlation was estimated between RCDI and COUNT while Poisson regression was used to model the differences in the comorbidity indices between race groups. Results 453 EMRAC subjects were analyzed; 342 (81.4%) were female, average age was 58.9 (± 15.1) years, average duration 13.3 (±11.1) years and average follow-up length 2.1 (±1.4) years. Individual comorbid frequencies as well as comorbid indices are summarized in Table 1. Spearman correlation between overall RDCI and COUNT was 0.90 (95% CI [0.88, 0.91], P Conclusions In an ethnic RA subset, the RCDI and COUNT correlated well across ethnic groups. The comorbidity indices were not associated with RA disease activity at enrollment as assessed by the RAPID3. Hispanics had lower RCDI and COUNT scores compared to other race groups but also presented at a younger age which could account for this difference. More studies are needed to determine the predictive value of these indices in determining poor outcomes and mortality in this ethnic subset. References England, BR et al. Arthritis Care Res. 2015 Jun; 67(6): 885–872. Disclosure of Interest S. Dowell Grant/research support from: Bristol Myers Squibb, Pfizer, Genentech, Speakers bureau: Horizon Pharma, G. Kerr Grant/research support from: Bristol Myers Squibb, Pfizer, Genentech, C. Swearingen Grant/research support from: Bristol Myers Squibb, Pfizer, Genentech, M. Quinones Grant/research support from: Bristol Myers Squibb, Pfizer, Genentech, J. Berrian Grant/research support from: Bristol Myers Squibb, Pfizer, Genentech, S. Hochberg Grant/research support from: Bristol Myers Squibb, Pfizer, Genentech

The RACAT (Rheumatoid Arthritis Comparison of Active Therapies) trial found triple therapy to be noninferior to etanercept-methotrexate in patients with active rheumatoid arthritis (RA).To determine the cost-effectiveness of etanercept-methotrexate versus triple therapy as a first-line strategy.A within-trial analysis based on the 353 participants in the RACAT trial and a lifetime analysis that extrapolated costs and outcomes by using a decision analytic cohort model.The RACAT trial and sources from the literature.Patients with active RA despite at least 12 weeks of methotrexate therapy.24 weeks and lifetime.Societal and Medicare.Etanercept-methotrexate first versus triple therapy first.Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs).The within-trial analysis found that etanercept-methotrexate as first-line therapy provided marginally more QALYs but accumulated substantially higher drug costs. Differences in other costs between strategies were negligible. The ICERs for first-line etanercept-methotrexate and triple therapy were $2.7 million per QALY and $0.98 million per QALY over 24 and 48 weeks, respectively. The lifetime analysis suggested that first-line etanercept-methotrexate would result in 0.15 additional lifetime QALY, but this gain would cost an incremental $77 290, leading to an ICER of $521 520 per QALY per patient.Considering a long-term perspective, an initial strategy of etanercept-methotrexate and biologics with similar cost and efficacy is unlikely to be cost-effective compared with using triple therapy first, even under optimistic assumptions.Data on the long-term benefit of triple therapy are uncertain.Initiating biologic therapy without trying triple therapy first increases costs while providing minimal incremental benefit.The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, Canadian Institutes for Health Research, and an interagency agreement with the National Institutes of Health-American Recovery and Reinvestment Act.

Objective To evaluate the association of hydroxychloroquine (HCQ) use with lipid profiles in a Veterans Affairs Rheumatoid Arthritis (VARA) cohort. Methods Lipid profiles in HCQ users were compared with HCQ nonusers, adjusting for potential confounders (age, sex, race, disease activity, prednisone, disease-modifying antirheumatic drugs, diabetes mellitus, and statin use). Applying current National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines for reduction of cardiovascular disease (CVD) events risk, the frequency of target lipid profiles with HCQ status was evaluated. Varied periods of HCQ exposure were compared to ascertain pharmacologic associations with lipid values. CVDs were compared between HCQ users and nonusers. Results In an elderly, predominantly male VARA cohort, 1,011 patients had lipid profiles; 787 patients (77.8%) were white. Statin use was recorded in 11.6% of patients, diabetes mellitus in 33.5%, and CVD in 31.2%. HCQ users (n = 150) were older, had longer rheumatoid arthritis (RA) disease duration, and had lower disease activity. Optimum lipid profiles, including total cholesterol:high-density lipoprotein (HDL) and HDL:low-density lipoprotein ratios (P ≤ 0.001), were more frequent in HCQ users, with the exception of HDL (P = 0.165), and persisted in multivariate analyses. Similarly, more HCQ users had NCEP-ATP III target levels. Varied periods of HCQ exposure suggested lipid changes to occur early, but lost within a year of drug discontinuation. HCQ users had less prevalent CVD. Conclusion In RA patients, HCQ use of at least 3 months' duration was associated with better lipid profiles irrespective of disease activity or statin use. Given the increased CVD risks in RA and the relative low cost and toxicity of HCQ, continued use, regardless of treatment regimen, should be considered.

Periodontitis (PD) has emerged as a risk factor in a number of health conditions including rheumatoid arthritis (RA) (1). Sharing both morphologic and histopathologic similarities with RA (2), PD is an inflammatory disease initiated by bacterial infection resulting in soft and hard tissue destruction and ultimately leading to tooth loss. In addition to shared inflammatory pathways, PD and RA share risk factors for susceptibility and progression, most notably cigarette smoking and, possibly, shared epitope-containing HLA-DRB1 alleles, the latter associated with localized aggressive periodontitis (3–10). Although a causal link between these conditions has not been established, several reports have demonstrated an increased PD prevalence in RA patients compared to controls (11–18). Growing evidence suggests that pathogens associated with PD could play a role in RA propagation. Chief among the organisms of interest is Porphyromonas gingivalis (P. gingivalis) (19). P. gingivalis is the only known pathogen expressing peptidylarginine deiminase (PPAD). Similar to its human counterpart, P. gingivalis-expressed PAD catalyzes the citrullination of arginine-containing peptides. This is noteworthy because citrullinated antigens are thought to drive adaptive immune responses that are nearly exclusive to RA. The potential role of P. gingivalis in RA pathogenesis has been borne out in epidemiologic investigations. Concentrations of circulating antibody to P. gingivalis have been demonstrated to be associated with the expression of anti-citrullinated peptide antibody (ACPA) (20–22). More recently, our group has shown that antibody to P. gingivalis is associated with the presence of RA-related autoantibody (a combination of rheumatoid factor [RF] and/or ACPA) among individuals at increased risk for disease but who have not yet developed RA symptoms (23), underscoring the potential role of this pathogen in RA development. As part of the present study, we conducted a large case-control investigation to examine the relationship of PD with established RA. We sought to examine the degree to which this relationship is impacted by shared genetic and/or environmental factors. We also sought to elucidate the degree to which the relationship of PD with RA may be related to infection and/or colonization with P. gingivalis. By using a rigorously selected control population, we attempted to mitigate issues of bias or unmeasured confounding that may have impacted other efforts often using healthy volunteers as comparators (16–18). Finally, using a multiplex approach, we examined the associations of PD and P. gingivalis with autoreactivity to several citrullinated autoantigens that have been implicated in RA disease pathogenesis.

Objective The co-occurrence of rheumatoid factor (RF) and anti–citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA-associated inflammation. Methods In a cohort of 1,488 US veterans with RA, measures of disease activity and serum levels of cytokines and multiplex ACPAs were compared between the following groups of patients: double-negative (anti–cyclic citrullinated peptide [anti-CCP]−/RF−), anti-CCP+/RF−, anti-CCP−/RF+, or double-positive (anti-CCP+/RF+). Additional studies were performed using an in vitro immune complex (IC) stimulation assay in which macrophages were incubated with ACPA ICs in the presence or absence of monoclonal IgM-RF, and tumor necrosis factor α production measured as a readout of macrophage activation. Results Compared with the double-negative subgroup (as well as each single-positive subgroup), the double-positive subgroup exhibited higher disease activity as well as higher levels of C-reactive protein and inflammatory cytokines (all P < 0.001). In vitro stimulation of macrophages by ACPA ICs increased cytokine production, and the addition of monoclonal IgM-RF significantly increased macrophage tumor necrosis factor α production (P = 0.003 versus ACPA ICs alone). Conclusion The combined presence of ACPAs and IgM-RF mediates increased proinflammatory cytokine production in vitro and is associated with increased systemic inflammation and disease activity in RA. Our data suggest that IgM-RF enhances the capacity of ACPA ICs to stimulate macrophage cytokine production, thereby providing a mechanistic link by which RF enhances the pathogenicity of ACPA ICs in RA.

The osteoporosis self-assessment tool (OST) is a screening instrument that uses age and weight as parameters to predict the risk of osteoporosis. This study was designed to evaluate OST in predicting osteoporosis in males. Male veterans aged 50yr and older with no prior diagnosis of osteoporosis and no prior bone densitometry (dual-energy X-ray absorptiometry [DXA]) testing were eligible for the study. Sociodemographic information, medical history, and risk factors for osteoporosis were recorded. Anthropometric measurements were taken and DXA testing performed. The OST index for each subject was calculated and predictive values and receiver operating characteristic (ROC) curves were evaluated for OST and osteoporosis. Five hundred eighteen subjects underwent DXA, 92 (17.8%) had osteoporosis, 281 (54.2%) had low bone mass, and 145 (28.0%) had normal bone mineral density. The OST index ranged from −8 to 23 with a mean of 4 (standard deviation ± 4.3). An OST index of 6 or lower predicted osteoporosis with a sensitivity of 82.6%, specificity of 33.6%, and an area under the curve for the ROC curve of 0.67. OST index performed better in non-Hispanic whites and males >65yr. OST predicts osteoporosis with moderate sensitivity and poor specificity in men.

In the United States, there is racial/ethnic disparity in the care of rheumatoid arthritis (RA), yet there are limited data regarding the impact of varied health care systems on treatment outcomes.The aim fo this study was to compare the frequencies of use of disease-modifying antirheumatic drugs and biologic agents in racial minorities with RA in a single-payer and variable-access health systems.Rheumatoid arthritis disease status was examined in the Ethnic Minority Rheumatoid Arthritis Consortium (EMRAC) and Veterans Affairs Rheumatoid Arthritis Registry (VARA); frequencies of prednisone and disease-modifying antirheumatic drugs and biologic agent use at enrollment were documented. Comparisons in frequencies of RA therapies between RA cohorts and white and nonwhite racial subsets were evaluated.The combined cohorts provided 2899 subjects for analysis (EMRAC = 943, VARA = 1956). Routine Assessment of Patient Index Data 3 and Disease Activity Score in 28 Joints scores were equivalent (cohort, racial subsets), as was biologic agent use (26% vs. 28%) between whites and nonwhites. Disease-modifying antirheumatic drug use was greater in EMRAC nonwhites compared with their white counterparts, but similar to all VARA patients (33% vs. 22% [P0.001], 36%, 39%, respectively). However, biologic agent use was significantly greater in EMRAC versus VARA patients (37% vs. 22%, P0.001). In VARA patients, there was no difference in biologic agent use among racial subsets (22% vs. 21%). In EMRAC patients, biologic agent use was greater in whites than in nonwhites (EMRAC white 45% vs. EMRAC nonwhite 33%, P0.001; odds ratio, 1.66) and compared with all VARA subjects (EMRAC white 45% vs. all VARA 22%, P0.001; odds ratio, 2.91). Younger age, advanced education, longstanding disease, and severe disease were associated with biologic agent use.When compared with more variable-access systems, a VA system of care that includes a single-payer insurance may afford equality in use of biologic agents among different racial subsets.

Objective To examine associations of body mass index (BMI) and weight loss with cause-specific mortality in rheumatoid arthritis (RA). Methods A cohort of US veterans with RA was followed until death or through 2013. BMI was categorized as underweight, normal, overweight, and obese. Weight loss was calculated as the 1) annualized rate of change over the preceding 13 months, and 2) cumulative percent. Vital status and cause of death were obtained from the National Death Index. Multivariable competing-risks regression models were utilized to assess the time-varying associations of BMI and weight loss with cause-specific mortality. Results Among 1,600 participants and 5,789 patient-years of followup, 303 deaths occurred (95 cardiovascular, 74 cancer, and 46 respiratory). The highest weight-loss rate and weight-loss percent were associated with a higher risk of cardiovascular mortality (rate: subdistribution hazard ratio [sHR] 2.27 [95% confidence interval (95% CI) 1.61–3.19]; percent: sHR 2.31 [95% CI 1.06–5.01]) and cancer mortality (rate: sHR 2.36 [95% CI 1.11–5.01]; percent: sHR 1.90 [95% CI 1.00–3.62]). Overweight BMI was protective of cardiovascular mortality (sHR 0.59 [95% CI 0.38–0.91]), while underweight BMI was associated with a near 3-fold increased risk of respiratory mortality (sHR 2.93 [95% CI 1.28–6.67]). Incorporation of time-varying BMI and weight loss in the same models did not substantially alter individual associations for cardiovascular and cancer mortality, but an association between weight-loss percentage and respiratory mortality was attenuated after BMI adjustment. Conclusion Both BMI and weight loss are predictors of cause-specific mortality in RA. Weight loss is a strong predictor of cardiovascular and cancer mortality, while underweight BMI is a stronger predictor of respiratory mortality.

Objective.C677T and A1298C polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with increased cardiovascular (CV) events in non-rheumatoid arthritis (RA) populations. We investigated potential associations of MTHFR polymorphisms and use of methotrexate (MTX) with time-to-CV event in data from the Veterans Affairs Rheumatoid Arthritis (VARA) registry.Methods.VARA participants were genotyped for MTHFR polymorphisms. Variables included demographic information, baseline comorbidities, RA duration, autoantibody status, and disease activity. Patients’ comorbidities and outcome variables were defined using International Classification of Diseases-9 and Current Procedural Terminology codes. The combined CV event outcome included myocardial infarction (MI), percutaneous coronary intervention, coronary artery bypass graft surgery, and stroke. Cox proportional hazards regression was used to model the time-to-CV event.Results.Data were available for 1047 subjects. Post-enrollment CV events occurred in 97 patients (9.26%). Although there was a trend toward reduced risk of CV events, MTHFR polymorphisms were not significantly associated with time-to-CV event. Time-to-CV event was associated with prior stroke (HR 2.01, 95% CI 1.03–3.90), prior MI (HR 1.70, 95% CI 1.06–2.71), hyperlipidemia (HR 1.57, 95% CI 1.01–2.43), and increased modified Charlson-Deyo index (HR 1.23, 95% CI 1.13–1.34). MTX use (HR 0.66, 95% CI 0.44–0.99) and increasing education (HR 0.87, 95% CI 0.80–0.95) were associated with a lower risk for CV events.Conclusion.Although MTHFR polymorphisms were previously associated with CV events in non-RA populations, we found only a trend toward decreased association with CV events in RA. Traditional risk factors conferred substantial CV risk, while MTX use and increasing years of education were protective.