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

BACKGROUND: The US Department of Veterans Affairs has created a portfolio of educational programs to train primary care providers (PCPs) in the evaluation and management of common musculoskeletal (MSK) conditions. Appropriate resource utilization for evaluation of knee pain, including limiting unnecessary magnetic resonance imaging (MRI) studies, is an important theme of these initiatives. The objective of this study was to report the utilization of knee MRI by PCP providers before and after the MSK education program and to determine the appropriateness of these MRI orders. METHODS: Twenty-six PCPs participated in the MSK Mini-Residency educational program held in Salt Lake City between April 2012 and October 2014. Knee MRI orders submitted by these providers 12 months before and 12 months after their participation were reviewed. Magnetic resonance imaging orders were categorized as “inappropriate,” “probably inappropriate,” or “possibly appropriate,” based on accepted guidelines for knee MRI utilization. Differences in the numbers of precourse and postcourse MRI orders for each of these categories were compared using Student t test. RESULTS: Following our program, MRI orders decreased from 130 (precourse) to 93 (postcourse), a reduction of 28% (p = 0.04). This reduction was observed entirely within the “inappropriate” and “probably inappropriate” categories; the number of orders categorized as “possibly appropriate” increased, but not significantly. CONCLUSIONS: The MSK Mini-Residency training program was a successful educational intervention and was associated with a reduction in inappropriate knee MRI utilization for some participants, while keeping appropriate MRI utilization stable.

Colon cancer–specific antigen (CCSA)-3 and CCSA-4 are novel colon cancer markers identified by focused proteomic analysis of nuclear structural proteins. The goal of these studies was to evaluate serum-based CCSA-3 and CCSA-4 in the detection of individuals with preneoplastic and neoplastic lesions using ELISAs. Serum samples from 107 subjects undergoing colonoscopy, 28 subjects with colorectal cancer, and 125 subjects with benign disease or other types of cancer were evaluated. Individuals who underwent colonoscopy were classified into mutually exclusive categories, including normal colon, hyperplastic polyp, nonadvanced adenoma, and advanced adenoma. Sensitivity and specificity for both CCSA-3 and CCSA-4 were evaluated using receiver operating characteristic (ROC) curves. At a cutoff of 2 μg/mL for CCSA-3 and 0.3 μg/mL for CCSA-4, each marker detected all 28 colorectal cancers, for a sensitivity of 100% (lower 95% confidence bound, 89.8%). The sensitivity for detection of the combined end point of colorectal cancer and advanced adenoma for CCSA-3 was 89.1% [95% confidence interval (95% CI), 76.4–96.4%] and for CCSA-4 was 84.8% (95% CI, 71.1–93.7%) and 91.3% (95% CI, 79.2–97.6%) for either marker positive. The specificity in individuals with normal, hyperplastic polyps, or nonadvanced adenomas was 82.0% (95% CI, 72.4–89.4%) and 91.0% (95% CI, 83.0–96.0%) for CCSA-3 and CCSA-4, respectively. ROC curves for CCSA-3 and CCSA-4 reveal an area under the curve of 0.94 (95% CI, 0.90–0.98%). In these initial analyses, CCSA-3 and CCSA-4 show promise as potential serum markers for detection of colorectal cancer and advanced adenomas. [Cancer Res 2007;67(12):5600–5]

Supplementary Figures 1-2 from Initial Analyses of Colon Cancer–Specific Antigen (CCSA)-3 and CCSA-4 as Colorectal Cancer–Associated Serum Markers

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

OBJECTIVE To examine the impact of major therapeutic change (MTC) on clinical response across a broad range of disease activity in US veterans with rheumatoid arthritis (RA). METHODS This historical cohort analysis evaluated patient visits from the Veterans Affairs RA registry between January 1, 2006 and September 30, 2017. Eligible patient visits were a rheumatology visit with 3 disease activity measures, including the Disease Activity Score in 28 joints, the Clinical Disease Activity Index, and the Routine Assessment of Patient Index Data 3; the follow-up visit for all 3 disease activity measures was 2-6 months later. The full population and a subset of patients with active disease (≥6 tender joints, ≥6 swollen joints) were evaluated. Clinical outcome was based on the American College of Rheumatology criteria for 20% improvement in disease activity (ACR20). The effect of MTC on ACR20 response was presented as crude descriptive statistics and evaluated using standardized regression for population- and disease activity-level conditional effects. RESULTS The full population comprised 1,208 patients (6,138 visits) and the active disease subpopulation included 383 patients (1,109 visits). Overall, visits with MTC were associated with increased likelihood of ACR20 response across all disease activity measures for the full population. Risk ratios for overall risk of ACR20 response for visits with MTC versus those without MTC ranged from 1.67 to 2.22 across disease activity measures among the full population and from 1.51 to 1.60 for the subpopulation with active disease. CONCLUSION MTC was associated with clinical improvement, even among patients with longstanding RA who had received multiple prior therapies, which emphasizes the utility of therapy modifications for patients with established and active 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.

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.

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: 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.

BACKGROUND: The relative efficacy and safety of allopurinol and febuxostat when used according to current guidelines for the treatment of hyperuricemia are unknown. This double-blind noninferiority trial examined these issues. METHODS: Participants with gout and hyperuricemia (with at least 33% having stage 3 chronic kidney disease) were randomly assigned to allopurinol or febuxostat in this 72-week trial, with doses titrated to target serum urate. The trial had three phases: titration (weeks 0 to 24), maintenance (weeks 25 to 48), and observation (weeks 49 to 72). Allopurinol and febuxostat were initiated at daily doses of 100 and 40 mg, with maximum titration to 800 and 120 mg, respectively. Antiinflammatory prophylaxis was given during phases 1 and 2. The primary end point was the proportion of patients experiencing one or more flares during phase 3, with a prespecified noninferiority margin of less than 8 percentage points between allopurinol and febuxostat. Secondary end points included efficacy in patients with chronic kidney disease, proportion achieving target serum urate levels, and serious adverse events. RESULTS: This study included 940 participants; 20.1% withdrew, with similar proportions in treatment arms. During phase 3, 36.5% of allopurinol-treated participants had one flare or more compared with 43.5% of febuxostat-treated participants (P

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.

Objective.Observational axial spondyloarthritis (axSpA) research in large datasets has been limited by a lack of adequate methods for identifying patients with axSpA, because there are no billing codes in the United States for most subtypes of axSpA. The objective of this study was to develop methods to accurately identify patients with axSpA in a large dataset.Methods.The study population included 600 chart-reviewed veterans, with and without axSpA, in the Veterans Health Administration between January 1, 2005, and June 30, 2015. AxSpA identification algorithms were developed with variables anticipated by clinical experts to be predictive of an axSpA diagnosis [demographics, billing codes, healthcare use, medications, laboratory results, and natural language processing (NLP) for key SpA features]. Random Forest and 5-fold cross validation were used for algorithm development and testing in the training subset (n = 451). The algorithms were additionally tested in an independent testing subset (n = 149).Results.Three algorithms were developed: Full algorithm, High Feasibility algorithm, and Spond NLP algorithm. In the testing subset, the areas under the curve with the receiver-operating characteristic analysis were 0.96, 0.94, and 0.86, for the Full algorithm, High Feasibility algorithm, and Spond NLP algorithm, respectively. Algorithm sensitivities ranged from 85.0% to 95.0%, specificities from 78.0% to 93.6%, and accuracies from 82.6% to 91.3%.Conclusion.Novel axSpA identification algorithms performed well in classifying patients with axSpA. These algorithms offer a range of performance and feasibility attributes that may be appropriate for a broad array of axSpA studies. Additional research is required to validate the algorithms in other cohorts.

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

Summary An informatics-driven population bone health clinic was implemented to identify, screen, and treat rural US Veterans at risk for osteoporosis. We report the results of our implementation process evaluation which demonstrated BHT to be a feasible telehealth model for delivering preventative osteoporosis services in this setting. Purpose An established and growing quality gap in osteoporosis evaluation and treatment of at-risk patients has yet to be met with corresponding clinical care models addressing osteoporosis primary prevention. The rural bone health tea m (BHT) was implemented to identify, screen, and treat rural Veterans lacking evidence of bone health care and we conducted a process evaluation to understand BHT implementation feasibility. Methods For this evaluation, we defined the primary outcome as the number of Veterans evaluated with DXA and a secondary outcome as the number of Veterans who initiated prescription therapy to reduce fracture risk. Outcomes were measured over a 15-month period and analyzed descriptively. Qualitative data to understand successful implementation were collected concurrently by conducting interviews with clinical personnel interacting with BHT and BHT staff and observations of BHT implementation processes at three site visits using the Promoting Action on Research Implementation in Health Services (PARIHS) framework. Results Of 4500 at-risk, rural Veterans offered osteoporosis screening, 1081 (24%) completed screening, and of these, 37% had normal bone density, 48% osteopenia, and 15% osteoporosis. Among Veterans with pharmacotherapy indications, 90% initiated therapy. Qualitative analyses identified barriers of rural geography, rural population characteristics, and the infrastructural resource requirement. Data infrastructure, evidence base for care delivery, stakeholder buy-in, formal and informal facilitator engagement, and focus on teamwork were identified as facilitators of implementation success. Conclusion The BHT is a feasible population telehealth model for delivering preventative osteoporosis care to rural Veterans.

An informatics-driven population bone health clinic was implemented to identify, screen, and treat rural US Veterans at risk for osteoporosis. We report the results of our implementation process evaluation which demonstrated BHT to be a feasible telehealth model for delivering preventative osteoporosis services in this setting.An established and growing quality gap in osteoporosis evaluation and treatment of at-risk patients has yet to be met with corresponding clinical care models addressing osteoporosis primary prevention. The rural bone health tea m (BHT) was implemented to identify, screen, and treat rural Veterans lacking evidence of bone health care and we conducted a process evaluation to understand BHT implementation feasibility.For this evaluation, we defined the primary outcome as the number of Veterans evaluated with DXA and a secondary outcome as the number of Veterans who initiated prescription therapy to reduce fracture risk. Outcomes were measured over a 15-month period and analyzed descriptively. Qualitative data to understand successful implementation were collected concurrently by conducting interviews with clinical personnel interacting with BHT and BHT staff and observations of BHT implementation processes at three site visits using the Promoting Action on Research Implementation in Health Services (PARIHS) framework.Of 4500 at-risk, rural Veterans offered osteoporosis screening, 1081 (24%) completed screening, and of these, 37% had normal bone density, 48% osteopenia, and 15% osteoporosis. Among Veterans with pharmacotherapy indications, 90% initiated therapy. Qualitative analyses identified barriers of rural geography, rural population characteristics, and the infrastructural resource requirement. Data infrastructure, evidence base for care delivery, stakeholder buy-in, formal and informal facilitator engagement, and focus on teamwork were identified as facilitators of implementation success.The BHT is a feasible population telehealth model for delivering preventative osteoporosis care to rural Veterans.

Background A previous analysis of the Veterans Affairs Rheumatoid Arthritis (VARA) registry showed that more than half of the patients with rheumatoid arthritis (RA) did not receive a major therapeutic change (MTC) despite moderate or severe disease activity. We aimed to empirically determine disease activity thresholds associated with a decision by rheumatologists and nurse practitioners to institute a MTC in patients with RA and to report the impact of that change on RA disease activity. Methods We analyzed data from the VARA registry between January 1, 2006, and September 30, 2017. Eligible patients had a visit with 3 disease activity measures (DAMs) recorded: Disease Activity Score for 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3). The Youden Index was used to identify disease activity thresholds that best discriminated rheumatologist/nurse practitioner decision to initiate MTC. Clinical outcome was 20% improvement in the American College of Rheumatology criteria (ACR20 response). The effect of MTC on ACR20 response was presented as crude descriptive statistics and evaluated using G-computation for marginal and conditional effects with established disease activity level combined with an empirical threshold from Youden analysis. Results The study population comprised 1776 patients (12,094 visits: 3077 with MTC, 9017 without MTC). Empirical thresholds (95% bootstrap confidence interval with 1000 replications) for MTC were 4.03 (3.70–4.36) for DAS28, 12.9 (10.4–15.4) for CDAI, and 3.81 (3.32–4.30) for RAPID3. Visits with MTC had increased likelihood of ACR20 response: risk ratios for ACR20 response for visits with MTC vs without MTC ranged 1.2–2.6 across DAMs; risk differences ranged 0.2–14.5%. Conclusions MTC was associated with clinical improvement across all DAMs with the greatest change in patients with RA disease activity above the Youden threshold identified in this work. Trial registration VARA Registry, https://www.hsrd.research.va.gov/research/abstracts.cfm?Project_ID=2141698764

For its clinical, epidemiologic, educational, and health services research, evaluation, administrative, regulatory, and accreditation purposes, the perceptions survey is a data collection tool that...

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.

Objective.To evaluate the effect of access to and distance from rheumatology care on the use of disease-modifying antirheumatic drugs (DMARD) in US veterans with inflammatory arthritis (IA).Methods.Provider encounters and DMARD dispensations for IA (rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis) were evaluated in national Veterans Affairs (VA) datasets between January 1, 2015, and December 31, 2015.Results.Among 12,589 veterans with IA, 23.5% saw a rheumatology provider. In the general IA population, 25.3% and 13.6% of veterans were exposed to a synthetic DMARD (sDMARD) and biologic DMARD (bDMARD), respectively. DMARD exposure was 2.6- to 3.4-fold higher in the subpopulation using rheumatology providers, compared to the general IA population. The distance between veterans’ homes and the closest VA rheumatology site was < 40 miles (Near) for 55.9%, 40–99 miles (Intermediate) for 31.7%, and ≥ 100 miles (Far) for 12.4%. Veterans in the Intermediate and Far groups were less likely to see a rheumatology provider than veterans in the Near group (RR = 0.72 and RR = 0.49, respectively). Exposure to bDMARD was 34% less frequent in the Far group than the Near group. In the subpopulation who used rheumatology care, the bDMARD exposure discrepancy did not persist between distance groups.Conclusion.Use of rheumatology care and DMARD was low for veterans with IA. DMARD exposure was strongly associated with rheumatology care use. Veterans in the general IA population living far from rheumatology sites accessed rheumatology care and bDMARD less frequently than veterans living close to rheumatology sites.

OBJECTIVE Many veterans enrolled in Veterans Affairs (VA) health care systems also receive care through other health care systems. Both VA and non-VA health care use must therefore be considered when conducting research in this population. This study characterized dual-care utilization in veterans with rheumatoid arthritis (RA) and explored associations with RA disease activity. METHODS Through a questionnaire mailed to RA patients at 3 VA sites, veterans reported medical services by non-VA primary care and subspecialty providers, comorbidities, non-VA medications, and hospitalizations. Disease Activity Score in 28 joints (DAS28) and Multidimensional Health Assessment Questionnaire (MD-HAQ) scores were recorded during VA clinic visits, and respondent groups were compared. RESULTS Of the 510 participants surveyed, 318 (62%) responded. Respondents were older (ages 69 versus 66 years; P = 0.006), more likely nonsmokers (80% versus 67%; P = 0.001), and had lower disease activity (DAS28 3.3 versus 3.8; P

Objective To compare persistence and adherence to triple therapy with the nonbiologic disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), hydroxychloroquine, and sulfasalazine, versus a tumor necrosis factor inhibitor (TNFi) plus MTX in patients with rheumatoid arthritis (RA). Methods Administrative and laboratory data were analyzed for US Veterans with RA initiating triple therapy or TNFi + MTX between January 2006 and December 2012. Treatment persistence 365 days postindex was calculated using 3 definitions. Definition 1 required no gap in therapy of ≥90 days for any drug in the original combination. Definition 2 required no added or switched DMARD, no decrease to nonbiologic DMARD monotherapy, and no termination of all DMARD therapies. Definition 3 was similar to definition 2 but allowed a switch to another drug within the same class. Adherence used a proportion of days covered of ≥80%. Propensity-weighted analysis with matched weights was used to balance covariates. Results The analysis included 4,364 RA patients (TNFi + MTX, n = 3,204; triple therapy, n = 1,160). In propensity-weighted analysis, patients in the TNFi + MTX group were significantly more likely than patients in the triple therapy group to satisfy all persistence criteria in definition 1 (risk difference [RD] 13.1% [95% confidence interval (95% CI) 9.2–17.0]), definition 2 (RD 6.4% [95% CI 2.3–10.5]), and definition 3 (RD 9.5% [95% CI 5.5–13.6]). Patients in the TNFi + MTX group also exhibited higher adherence during the first year (RD 7.2% [95% CI 3.8–10.5]). Conclusion US Veterans with RA were significantly more likely to be persistent and adherent to combination therapy with TNFi + MTX than triple therapy with nonbiologic DMARDs.

Background Our recent work showed that 41% of patients with moderate/severe rheumatoid arthritis (RA) by Disease Activity Score for 28 joint count (DAS28) did not have changes in RA therapy as recommended by current guidelines (1). Reasons identified for the decision not to escalate therapy was provider’s opinion that RA disease was adequately controlled despite moderate/severe disease activity by DAS28, and that changes in therapy may not produce significant improvements in disease activity (1). Objectives 1) Compare short-term differences in ACR20 response between patients with and without a major therapeutic change (MTC) over a range of disease activity; 2) Determine whether ACR20 responses vary by disease activity measures (DAMs) used to assess disease activity (i.e., DAS28, Clinical Disease Activity Index [CDAI], Routine Assessment of Patient Index Data 3 [RAPID3]). Methods Each clinic visit for US Veterans enrolled in the VA Rheumatoid Arthritis (VARA) registry was evaluated if the visit had: 1) a complete set of DAMs (DAS28, CDAI, RAPID3) recorded; 2) two other visits with all DAMs during the preceding 18 months separated by at least 60 days and one visit with all DAMs between 60 and 180 days following the visit date; 3) clinical data available for 18 months prior to visit date; and 4) ≥6 tender and ≥6 swollen joints at visit date. Each patient was assessed for MTC within 1 week before and 30 days after visit date. MTC was defined as any of the following: 1) initiation of new biologic or nonbiologic disease-modifying antirheumatic drug (DMARD) or prednisone (as new agent or after 90-day gap during baseline); 2) escalation of DMARD dose by ≥25%; or 3) increase in monthly average prednisone dose by 25%; and/or 4) injection of 2 or more joints with corticosteroids. Clinical improvement was defined as an ACR20 response comparing each eligible visit DAM to the first follow-up visit DAM observed between 60 and 180 days of the eligible visit date. ACR20 response was compared between eligible visits with and without a MTC and stratified by quartiles of disease activity by each DAM. The Generalized Estimating Equations (GEE) model was fitted using the exchangeable working covariance structure to account for clustering of visits within patients. Models for each DAM were adjusted for age, disease duration, race, seropositive status, comorbidities, disease stability, and recent medication changes in the observations period prior to the visit date. Results There were 383 patients (92% were male, mean age was 62.9 years, mean disease duration was 12.5 years, 83% tested positive for rheumatoid factor, and 79% positive for anti-cyclic citrullinated peptide antibodies) who contributed 1,193 eligible visits. Visits with a MTC had a higher rate of ACR20 response in comparison to visits without a MTC at all levels of disease activity. A MTC at a visit with the highest disease activity (quartile 4) consistently had the largest proportion of follow-up visits with an ACR20 response. The overall effect for MTC was statistically significant across all 3 DAMs. Across quartiles, the MTC group consistently had a higher proportion of follow-up visits with ACR20 response compared to the group without a MTC. Risk Ratios from the adjusted analysis are presented in the table. Conclusion All patients with active RA have a significant potential to benefit with a MTC. This potential for improvement was seen across all degrees of disease activity and with all three DAMs. Reference [1] Stever, et al. Utility of administrative and clinical data to predict major change in medical treatment in US Veterans enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry. Clin Exp Rheumatol; 2018Epub ahead of print. Disclosure of Interests Grant Cannon Grant/research support from: Amgen Inc., Wei Chen Grant/research support from: Amgen Inc., Jincheng Shen: None declared, Neil Accortt Shareholder of: Amgen Inc., Employee of: Amgen Inc., David Collier Shareholder of: Amgen Inc., Employee of: Amgen Inc., Brian Sauer Grant/research support from: Amgen Inc.

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.

Background Delays in treatment for inflammatory arthritis (IA) are associated with unfavorable outcomes, including impaired quality of life, irreversible joint damage, and disability. Objectives To characterize treatment initiation patterns in patients with newly diagnosed rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Methods Incident IA cases were identified between January 1, 2007 and December 31, 2015, in patients enrolled in the Veteran Health Administration, using International Classification of Diseases codes and natural language processing. Patterns of treatment initiation and non-treatment with disease modifying anti-rheumatic drugs (DMARDs) were assessed in the 12-month follow-up period after the incident diagnosis. Results The population consisted of 12, 118 IA patients (9,711 RA, 1,472 PsA, 935 AS), with 91.3% males and a mean age of 63.7. In total, 58.2% of patients initiated a DMARD within 12 months after diagnosis (RA 60.0%, PsA 64.3%, AS 29.6%) (Figure). A DMARD was dispensed ≤30 days after IA diagnosis in 41.2% of patients and ≤90 days in 50.0% of patients. Rheumatology specialty care was accessed during the study period, prior to DMARD dispensation, by 82.7% of patients exposed to a non-biologic DMARD and 90.0% of patients exposed to a biologic DMARD. The percentage of IA patients with DMARD exposure during the 12-month follow-up period increased from 48.8% in 2008 to 66.4% in 2015. Conclusion Approximately one-half of patients received treatment with a DMARD within 90 days after their initial IA diagnosis. DMARD treatment rates during the initial 12 months after diagnosis increased between 2007 and 2015, but non-treatment remained common, particularly in patients with AS. Timely access to a rheumatology provider is likely important for early DMARD treatment. References [1] Ng, et al. BMJ Open. 3:e002468. Disclosure of Interests Jessica A. Walsh Grant/research support from: Abbvie, Pfizer , Consultant for: Abbvie, Celgene, Lilly, Novartis , Shaobo Pei: None declared, Gopi Penmetsa: None declared, Brian Sauer Grant/research support from: Amgen, Vikas Patil: None declared, Jodi Walker Shareholder of: Abbvie, Employee of: Abbvie, Jerry Clewell Shareholder of: Abbvie, Employee of: Abbvie, Kevin Douglas Shareholder of: Abbvie, Employee of: Abbvie, Daniel Clegg Grant/research support from: Amgen grant, Grant Cannon Grant/research support from: Amgen Inc., Ahmad Halwani Grant/research support from: Bristol-Myers Squibb, Kyowa Hakko Kirin, Roche, Abbvie, Genentech, Immune Design, miRagen, Amgen, Seattle Genetics, Takeda, Pharmacyclics

Recruiting professional staff is an important business reason for hospitals allowing health trainees to engage in supervised patient care. Whereas prior studies have focused on educational institutions, this study focuses on teaching hospitals and whether trainees' clinical experiences affect their willingness to work (ie, recruitability) for the type of healthcare center where they trained.A pre-post, observational study based on Learners' Perceptions Survey data in which respondents served as their own controls.Convenience sample of 15,207 physician, 11,844 nursing, and 13,012 associated health trainees who rotated through 1 of 169 US Department of Veterans Affairs (VA) medical centers between July 1, 2014, and June 30, 2017. Generalized estimating equations computed how clinical, learning, working, and cultural experiences influenced pre-post differences in willingness to consider VA for future employment.VA recruitability increased dramatically from 55% pretraining to 75% post training (adjusted odds ratio [OR], 2.1; 95% CI, 2.0-2.1; P.001) in all 3 cohorts: physician (from 39% to 59%; OR, 1.6; 95% CI, 1.5-1.6; P.001), nursing (from 61% to 84%; OR, 2.5; 95% CI, 2.4-2.6; P.001), and associated health trainees (from 68% to 87%; OR, 2.7; 95% CI, 2.6-2.9; P.001). For all trainees, changes in recruitability (P.001) were associated with how trainees rated their clinical learning environment, personal experiences, and culture of psychological safety. Satisfaction ratings with faculty and preceptors (P.001) were associated with positive changes in recruitability among nursing and associated health students but not physician residents, whereas nursing students who gave higher ratings for interprofessional team culture became less recruitable.Academic medical centers can attract their health trainees for future employment if they provide positive clinical, working, learning, and cultural experiences.

Background Psychological safety (PS) is the perception that it is safe to take interpersonal risks in the work environment. In teaching hospitals, PS may influence the clinical learning environment for trainees. Objective We assessed whether resident physicians believe they are psychologically safe, and if PS is associated with how they rate satisfaction with their clinical learning experience. Methods Data were extracted from the Learners' Perceptions Survey (LPS) of residents who rotated through a Department of Veterans Affairs health care facility for academic years 2011–2014. Predictors of PS and its association with resident satisfaction were adjusted to account for confounding and response rate biases using generalized linear models. Results The 13 044 respondents who completed the LPS (30% response rate) were comparable to nonpediatric, non–obstetrics-gynecology residents enrolled in US residency programs. Among respondents, 11 599 (89%) agreed that “. . . members of the clinical team of which I was part are able to bring up problems and tough issues.” Residents were more likely to report PS if they were male, were in a less complex clinical facility, in an other medicine or psychiatry specialty, or cared for patients who were aged, had multiple illnesses, or had social supports. Nonpsychiatric residents felt safer when treating patients with no concurrent mental health diagnoses. PS was strongly associated with how residents rated their satisfaction across 4 domains of their clinical learning experience (P Conclusions PS appears to be an important factor in resident satisfaction across 4 domains that evaluators of graduate medical education programs should consider when assessing clinical learning experiences.

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.

Purpose Medications with non-standard dosing and unstandardized units of measurement make the estimation of prescribed dose difficult from pharmacy dispensing data. A natural language processing tool named the SIG extractor was developed to identify and extract elements from narrative medication instructions to compute average weekly doses (AWDs) for disease-modifying antirheumatic drugs. The goal of this paper is to evaluate the performance of the SIG extractor. Method This agreement study utilized Veterans Health Affairs pharmacy data from 2008 to 2012. The SIG extractor was designed to extract key elements from narrative medication schedules (SIGs) for 17 select medications to calculate AWD, and these medications were categorized by generic name and route of administration. The SIG extractor was evaluated against an annotator-derived reference standard for accuracy, which is the fraction of AWDs accurately computed. Results The overall accuracy was 89% [95% confidence interval (CI) 88%, 90%]. The accuracy was ≥85% for all medications and route combinations, except for cyclophosphamide (oral) and cyclosporine (oral), which were 79% (95%CI 72%, 85%) and 66% (95%CI 58%, 73%), respectively. Conclusions The SIG extractor performed well on the majority of medications, indicating that AWD calculated by the SIG extractor can be used to improve estimation of AWD when dispensed quantity or days' supply is questionable or improbable. The working model for annotating SIGs and the SIG extractor are generalized and can easily be applied to other medications. Copyright © 2016 John Wiley & Sons, Ltd.

Objective Unintentional weight loss is important and can be predictive of long-term outcomes in patients with rheumatoid arthritis (RA). This study was undertaken to assess how primary therapies for RA may influence changes in body mass index (BMI) in RA patients from a large administrative database. Methods Unique dispensing episodes of methotrexate, prednisone, leflunomide, and tumor necrosis factor inhibitors (TNFi) administered to RA patients were identified from the US Department of Veterans Affairs pharmacy databases. Values for C-reactive protein (CRP) level and BMI closest to the time point within 30 days of the treatment course start date and at follow-up time points were linked. Missing laboratory values were imputed. Weight loss was defined as a decrease in BMI of >1 kg/m2. Regression models were used to evaluate changes in BMI during each drug treatment as compared to treatment with methotrexate. To assess the impact of confounding by indication, propensity scores for use of each drug were incorporated in analyses using matched-weighting techniques. Results In total, 52,662 treatment courses in 32,859 RA patients were identified. At 6 months from the date of prescription fill, weight gain was seen among patients taking methotrexate, those taking prednisone, and those taking TNFi. On average, compared to methotrexate-treated patients, prednisone-treated patients had significantly more weight gain, while leflunomide-treated patients demonstrated weight loss. In multivariable models, more weight loss (β = −0.41 kg/m2, 95% confidence interval [95% CI] −0.46, −0.36; P

A cost-effective professional development program enhancing musculoskeletal (MSK) skills of physicians and allied health providers working in primary care settings has been reported at a single site. This article describes the first 2 years of the national expansion and implementation of a 3-day “MSK Mini-residency.” Faculty from Veterans Affairs (VA) medical centers worked in partnership with national program faculty from the Salt Lake City VA to present an intensive, integrated, multidisciplinary program to strengthen the skills of primary care providers in evaluating and managing MSK conditions common in primary care. Course assessments included written surveys and a two-station observed structured clinical examination (OSCE) evaluating the physical examination of the shoulder and knee. In the first 2 years of the program, 13 VA facilities participated. Two hundred twenty-seven health care providers, including 135 physicians, were trained. Two hundred seven participants (91 %) completed all pre- and post-course written assessments and the two-station OSCE. The MSK Mini-residency program is an effective and well-received mixed-method educational initiative to strengthen the skills of primary care physicians and other health care providers in evaluating and managing patients with MSK complaints and to document their competence in performing physical examinations of the shoulder and knee. The 2-year experience in implementation suggests that this model of educational partnerships is a feasible approach to disseminating innovative educational programs in a way that preserves curricular consistency yet is adaptable to local needs.

Objectives The aim was to estimate the impact of TNF inhibitor (TNFi) exposure on radiographic disease progression in US Veterans with RA during the first year after initiating therapy. Methods This historical longitudinal cohort design used clinical and claims data to evaluate radiographic progression after initiation of TNFi. US Veterans with RA initiating TNFi treatment (index date), ≥ 6 months pre-index and ≥ 12 months post-index VA enrolment/activity, and initial (6 months pre-index to 30 days post-index) and follow-up (10–18 months post-index) bilateral hand radiographs were eligible. The cumulative TNFi exposure and change in modified Sharp score (MSS) between initial and follow-up radiographs were calculated. The percentage of patients with clinically meaningful change in MSS (≥ 5) for each month of exposure was assessed using a longitudinal marginal structural model with inverse probability of treatment weights. Mean values and CIs were generated using 1000 bootstrapped samples. Results For 246 eligible patients, the mean (s.d.) age was 58 (11) years; 81% were male. The mean (s.d.) initial MSS was 19.6 (33.4) (range 0–214). The mean change (s.d.) in MSS was 0.3 (3.6) (median 0, range −19 to 22). Patients with the greatest exposure had the least radiographic progression for both crude and adjusted model analyses. Adjusted rates of MSS change ≥ 5 points (95% CI) were 10.6% (9.8%, 11.4%) for patients with 3 months of exposure compared with 5.4% (5.1%, 5.7%) for patients with 12 months of exposure. Conclusion One-year changes in radiographic progression were small. Patients with the greatest cumulative TNFi exposure experienced the least progression.

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.

Background Current rheumatoid arthritis (RA) treatment guidelines recommend the use of disease activity measures (DAMs) to guide RA therapy. These guidelines recommend considering escalation of therapy in RA patients with high or moderate disease activity. Recent work by our group has demonstrated that many RA patients with high/moderate RA by Disease Activity Score with 28 joints (DAS28) did not have therapy escalated despite active disease (DAS28 ≥3.2). Objectives 1) To determine if the rate of major therapeutic change (MTC) for RA patients with high/moderate disease activity based on DAS28 was similar when measured using two other common DAMs; 2) to compare the ability of different DAMs to predict MTC across the full spectrum of RA disease activity. Methods US Veterans enrolled in the VA Rheumatoid Arthritis (VARA) registry with 1) a complete set of DAMs (DAS28, Clinical Disease Activity Index [CDAI], Routine Assessment of Patient Index Data 3 [RAPID3]) recorded (index date), 2) two other visits during the preceding 18 months separated by at least 60 days, and 3) clinical data available for 18 months prior to through 30 days following index date were eligible. Each patient was assessed for MTC within 1 week before and 30 days after index date. MTC was defined as any of the following: 1) initiation of new biologic or nonbiologic DMARD, 2) escalation of DMARD dose by ≥25%, 3) initiation of prednisone (as new agent or after 90 day gap during baseline), or 4) increase in monthly average prednisone dose by 25% and/or 5) injection of 2 or more joints with corticosteroids. MTC was analysed by DAM severity thresholds of 1) high, moderate, low, and remission, and 2) high, high/moderate, and high/moderate/low levels. Analyses of the latter thresholds included sensitivity, specificity, predictive values, and accuracy estimations for MTC at each DAM level. Results Of 1776 eligible patients, 89% were male, mean age was 63.4 years, mean disease duration was 13.4 years, 79% tested positive for rheumatoid factor, and 63% positive for anti-cyclic citrullinated peptide antibodies. Overall, 33.1% (591/1776) of patients had an MTC. A markedly larger percentage of patients with high disease activity had MTC (range 55.1%–43.5%) compared to patients with moderate disease (range 38.7%–27.8%) (table 1). Sensitivity, specificity, predictive values, and accuracy at each DAM threshold level varied markedly by DAM, with RAPID3 having a higher sensitivity, lower specificity, and less accuracy than DAS28 or CDAI (table 2). Conclusions Most patients with high/moderate disease activity did not have a MTC. This observation was consistent regardless of which DAM was utilised. MTC increased with disease activity with all DAMs; however, DAS28 and CDAI appeared to have greater accuracy than RAPID3 at predicting MTC at all disease severity thresholds. There is need for continued evaluation of DAM thresholds for defining disease activity for MTC decisions, better DAMs, and/or better application of DAMs in clinical practice to improve the treatment of patients with active RA. Acknowledgements This study was sponsored by Immunex, a subsidiary of Amgen. Medical writing assistance provided by Amgen. Disclosure of Interest G. Cannon Grant/research support from: Amgen, C.-C. Teng Grant/research support from: Amgen, N. Accortt Shareholder of: Amgen, Employee of: Amgen, D. Collier Shareholder of: Amgen, Employee of: Amgen, T.-C. Lin Shareholder of: Amgen, Employee of: Amgen, B. Sauer Grant/research support from: Amgen Inc.

To examine factors associated with major therapeutic changes (MTC) among US Veterans with moderate/severe rheumatoid arthritis (RA) based on Disease Activity Score based on 28 joints (DAS28).We used data from patients enrolled in the Veterans Affairs Rheumatoid Arthritis (VARA) registry from 1/1/2006 through 12/31/2014. The index date was a clinic visit with DAS283.2 (moderate/severe disease) following an 18-month pre-index period that included ≥2 DAS28 measurements ≥60 days apart. The patients were followed for MTC from 7 days pre-index through 90 days post-index. Poisson multivariable regression models were used to identify associations with MTC. Chart review of a subset of randomly selected patients explored factors that impacted therapeutic decisions.Among 941 patients, 396 (42.1%) had MTC. Of these, 369 (39.2%) patients had worsening DAS28 at index, 118 (12.5%) had DAS28 improvements, and 454 (48.2%) patients had no change in DAS28 versus pre-index DAS28. Of the patients with worsening DAS28, no change in DAS28, and improved DAS28, respectively, 50.5%, 62.6%, and 70.3% had no MTC. Regression analyses showed index DAS28, oral steroid or non-biologic disease-modifying anti-rheumatic drug (nbDMARD) use in the previous year were associated with an increased likelihood of MTC; use of nbDMARDs in the previous 90 days was associated with a decreased likelihood of MTC. The most common reason for not modifying therapy despite DAS283.2 was a judgement of mild disease.Clinicians frequently do not institute major therapeutic changes despite DAS28 indicating moderate/severe disease activity; multiple factors are involved in real-world treatment decisions.

OBJECTIVE: Obese patients with rheumatoid arthritis (RA) may be more likely to discontinue therapy than non-obese patients, possibly signifying a more refractory phenotype. The purpose of this study was to examine the association between body mass index (BMI) and discontinuation rates for different RA treatments accounting for confounding factors. METHODS: Veterans Affairs administrative databases were used to define initial courses of methotrexate (MTX), hydroxychloroquine, sulfasalazine, prednisone, and self-injectable tumour necrosis factor inhibitors (TNFi). Discontinuation was defined as a lapse in drug refill >90 days. Using overweight BMI (25–30 kg/m(2)) as the referent group, multivariable Cox proportional hazards models were used to evaluate associations between BMI category and time to treatment discontinuation. RESULTS: There were 46,970 initial RA treatment courses identified from 2005–2014 among 23,669 Veterans with RA. In multivariable models, severe obesity (BMI >35 kg/m(2)), compared to overweight BMI, was not associated with treatment discontinuation with the exception of prednisone [HR 1.10 (1.04, 1.17) p

Background Big data research is important for studying uncommon diseases in real-world settings. Most big data studies in axial spondyloarthritis (axSpA) have been limited to populations identified with billing codes for ankylosing spondylitis (AS). axSpA is a more inclusive concept, and reliance on AS codes does not produce a comprehensive axSpA study population. The first objective was to describe our process for establishing an appropriate sample of patients with and without axSpA for developing accurate axSpA identification methods. The second objective was to determine the classification performance of AS billing codes against the chart-reviewed axSpA reference standard. Methods Veteran Health Affairs clinical and administrative data, between January 2005 and June 2015, were used to randomly select patients with clinical phenotypes that represented high, moderate, and low likelihoods of an axSpA diagnosis. With chart review, the sampled patients were classified as Yes axSpA, No axSpA or Uncertain axSpA, and these classification assignments were used as the reference standard for determining the positive predictive value (PPV) and sensitivity of AS ICD-9 codes for axSpA. Results Six hundred patients were classified as Yes axSpA (26.8%), No axSpA (68.3%), or Uncertain axSpA (4.8%). The PPV and sensitivity of an AS ICD-9 code for axSpA were 83.3% and 57.3%, respectively. Conclusions Standard methods of identifying axSpA patients in a large dataset lacked sensitivity. An appropriate sample of patients with and without axSpA was established and characterized for developing novel axSpA identification methods that are anticipated to enable previously impractical big data research.