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The clinical profile of patients with obstructive hypertrophic cardiomyopathy (oHC) is not well characterized, with little evidence outside selected referral populations. Using longitudinal medical claims data from a United States nationwide database, we retrospectively identified adults who were newly diagnosed with oHC. Clinical characteristics were compared from 1 year before diagnosis and at the 2-year follow-up. Patients (N = 1,841) with oHC (age 63 ± 15 years; 52% were male) with geographic representation across the United States were identified. Most patients received care within community-based cardiovascular practices and 7% at referral hypertrophic cardiomyopathy (HC) centers. Baseline diagnostic procedures included electrocardiogram (66%), echocardiogram (51%), magnetic resonance imaging (4%), and HC genetic testing (0.7%). Baseline co-morbidities were hypertension (59%), coronary artery disease (30%), diabetes (19%), and atrial fibrillation (19%). For all HC-related medications, use significantly increased after diagnosis. During follow-up, 144 patients (8%) received an implantable cardioverter-defibrillator for sudden death prevention, 99 underwent septal myectomy (5%), and 24 underwent alcohol septal ablation (1%). By the 1-year follow-up, 2% of patients had sudden cardiac arrest and 26% had atrial fibrillation, and heart failure increased from 16% to 27%. In conclusion, in a community-based population of patients with oHC, patients' age at diagnosis of oHC was older than reported for referral populations and patients had a significant co-morbidity burden. Cardiovascular medication use was appropriate, but the rate of guideline-supported surgical procedures was low.

Helen Hahn,1 Tzy-Chyi Yu,1 Chia-Chen Teng,2 Hiangkiat Tan2 1Mallinckrodt Pharmaceuticals, Hampton, NJ, USA; 2Healthcore, Inc., Wilmington, DE, USACorrespondence: Tzy-Chyi Yu, Mallinckrodt Pharmaceuticals, Shelbourne Building, 53 Frontage Road, Suite 300, Hampton, NJ, 08827, USA, Tel +1 908 238 6884, Email amanda.yu@mnk.comAim: This retrospective observational study provides a holistic view of the clinical and economic characteristics of inpatient treatment of patients with thermal burns undergoing autografting, by integrating real-world data (RWD) from medical records from healthcare providers (HCPs) and administrative claims.Methods: We identified eligible patients between July 1, 2010, and November 30, 2019, from the HealthCore Integrated Research Database® (HIRD®) and obtained their medical records from HCPs. We abstracted data from medical records to describe patient demographics and clinical characteristics and obtained costs of treatment from claims.Results: Two hundred patients were stratified into cohorts based on the percentage of total body surface area (%TBSA) burned: minor (< 10%), moderate (10%– 24%), and major (≥ 25%). Data obtained from medical records and administrative claims were comparable to previous findings from administrative claims data. This privately insured study cohort predominantly consisted of White men. Diabetes mellitus and hypertension were frequently reported in a relatively young population. Key clinical characteristics that could influence burn treatment decisions and long-term outcomes, such as body mass index, size of autograft donor site, and mesh ratio, were frequently underdocumented in patients’ medical records.Conclusion: Evidence generated from 2 orthogonal RWD sources confirmed that patients with larger %TBSA burned required more intensive care, thereby incurring higher costs. This study highlights considerable incompleteness in many critical fields in medical records, which limits the ability to generate broader insights. More comprehensive documentation of clinical characteristics and outcomes of autografts and donor sites in the operative and medical notes is critical to appropriately evaluate their impact on outcomes of burn treatments in future research using RWD.Keywords: burn injury, healthcare resource utilization, treatment patterns, real-world data

Hypertrophic cardiomyopathy (HC) is a common genetic heart disease. However, the number of gene mutation carriers who develop HC and manifest clinical symptoms is not well established. Our objective was to estimate annual prevalence and incidence rates of clinically diagnosed HC in the United States. Data from the HealthCore Integrated Research Database (HIRD) were interrogated for years 2013-2019 to identify patients with ≥1 claim of HC International Classification of Diseases, Clinical Modification Ninth and Tenth Revision diagnosis codes. In 2013, among 16,243,109 patients, 8,526 were identified with HC, yielding an estimated prevalence of clinically diagnosed HC of 0.052% (0.035% for obstructive [oHC], 0.017% for nonobstructive [nHC]). This prevalence yielded an estimated 164,403 patients with clinical diagnosis of HC. For the same year, the incidence of new HC diagnoses was 0.030% (0.020% for oHC, 0.010% for nHC). Over the following 6 years, prevalence and incidence of HC increased by 0.005%/year (p

Patients with obstructive hypertrophic cardiomyopathy (oHCM) and severe refractory symptoms may require invasive septal reduction therapies (SRTs), either surgical septal myectomy (SM) or transcatheter alcohol septal ablation (ASA). The main objective of this study was to quantify all-cause and oHCM-related healthcare resource utilization (HCRU) and costs for patients receiving SM or ASA.This retrospective study utilized medical and pharmacy claims submitted during 2012-2020. HCRU and costs for 119 adults with oHCM who had at least 1 SM (n = 95) or ASA (n = 24) were compared for baseline and follow-up periods.The mean inpatient hospitalization stay was longer for SM (8.3 days) than ASA (6.0 days). Postprocedure HCM-related medication usage was greater following SM (98%) than ASA (88%). The mean number of HCM-related outpatient visits increased from pre- to post procedure (12.2 vs 15.9 in the SM group; 7.2 vs 9.5 in the ASA group), with most patients having at least 1 cardiology visit post procedure (86% of the SM group; 83% of the ASA group). Total mean HCM-related costs (reported in United States currency) increased with both procedures ($27,045 vs $119,772 in the SM group; $11,278 vs $54,351 in the ASA group), driven by increased inpatient hospitalization ($10,325 vs $112,923 in the SM group; $5509 vs $47,450 in the ASA group) and surgical costs ($6665 vs $92,031 in the SM group; $52 vs $44,815 in the ASA group).Our results indicate increasing costs for patients undergoing SRT, driven by inpatient hospitalizations and surgical costs. Commercially insured and Medicare Advantage patients with oHCM experience high healthcare costs and economic burden attributable to SRT.

This paper examines the ways in which three external governance mechanisms, namely market preferences, institutional investors, and debtholder monitoring, influence dividend payout decisions under a family-governance system. We find that family firms issue lower dividends when the dividend premium is high in the market. Institutional investors and family-controlled governance mechanisms interact to increase dividend payouts. Family firms under greater debtholder monitoring pay out more cash to shareholders. Our findings generate important policy implications.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently used medications for pain, even though they increase the risk for adverse cardiovascular events.The objective of this study was to determine cardiovascular, cerebrovascular, and renal event rates between NSAIDs versus NSAIDs plus misoprostol.A population-based historical cohort of U.S. veterans receiving prescription NSAIDs (1,681,609) versus NSAIDs plus misoprostol (5972 misoprostol users) was followed for 5 years. In an intent-to-treat analysis, NSAID and NSAID plus misoprostol groups were compared using propensity score-weighted Poisson regression models to estimate incident rate ratio (IRR) and Cox regression to estimate hazard ratio (HR).The most prescribed NSAIDs were diclofenac and ibuprofen. The mean follow-up was 35.2 ± 14.5 months. There were 439 total cardio-renal events (5.62/1000 patient-months) in the NSAID group and 419 patients (5.01/1000 patient-months) in the NSAID plus misoprostol group (Hazard Ratio (HR): 0.89; 95% confidence interval [CI]: 0.78-1.019; p = 0.09). The risk of cardiovascular event was lower in the NSAID plus misoprostol group (HR: 0.56; 95% CI: 0.34-0.93; p 0.0001). Cerebrovascular event rates were lower in the NSAID plus misoprostol group (HR: 0.74; 95% CI: 0.60-0.94, p 0.0001) and for renal (HR: 0.67; 95% CI: 0.49-0.89, p 0.0001) events. All-cause mortality rate was not different between the two groups (HR: 1.05; 95% CI: 0.88-1.25, p = 0.61).Compared with NSAID use alone, the concomitant use of NSAID plus misoprostol is associated with a reduced risk of NSAID-induced cardiovascular, cerebrovascular, and renal adverse events. These data support the development of a safer NSAID when combined with misoprostol.

This study aimed to assess treatment patterns and frequency of inadequate response associated with advanced therapy initiation among patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in the USA.Adult patients with AS or PsA who initiated advanced therapy were identified from the HealthCore Integrated Research Database®. Inadequate response to advanced therapies (tumour necrosis factor inhibitors [TNFi] and non-TNFi biologics) was identified using a claims-based algorithm. Factors influencing inadequate response were assessed using multivariable logistic regression.In total, 646 patients with AS, and 1433 patients with PsA were evaluated. Among patients with AS (mean age, 43 years; male, 58%), 93% patients initiated TNFi, and 69% of patients had inadequate response. In patients with PsA (mean age, 49 years; male, 47%), 67% initiated TNFi, and 77% had inadequate response. Low adherence was the main predictor of inadequate response in patients with AS (56%) and PsA (63%). Inadequate responders were more likely to be female (odds ratio [OR] 2.05 for AS and 1.37 for PsA). Prior exposure to TNFi was associated with 3.89- and 2.14-fold greater odds of inadequate response in both AS and PsA patients, respectively, while patients using methotrexate were less likely to have inadequate response (OR 0.48 for AS and 0.72 for PsA; all p 0.05).Over 69% of patients with AS and 77% of patients with PsA had inadequate response to their index advanced therapy during 1 year after initiation. Health plan claims data appear useful to classify inadequate responders in AS and PsA. Key Points • Estimating inadequate response to advanced therapies and identifying factors associated with this outcome using claims data could improve treatment outcomes in AS and PsA. • In a sample of commercially insured US patients, over 69% of patients with AS and 77% of patients with PsA had inadequate response to their index advanced therapy during 1 year after initiation. Patient characteristics such as sex and prior therapy use were predictive of inadequate response to advanced therapies. • Health plan claims data appear useful to classify inadequate responders in AS and PsA and identify factors associated with this outcome.

The primary objective of this retrospective, observational study was to evaluate glycemic control over a 2 yr follow-up period among dulaglutide (DU) initiators with continuous treatment using U.S. claims data from the HealthCore Integrated Research Database (HIRD®) between May 2014 and May 2019 (index date=earliest DU fill during index period between November 2014 and May 2017). Patients (pts) ≥18 yrs old with T2D, ≥1 pharmacy claim for DU during the index period, continuous enrollment in the 6 months pre index (=baseline [BL]) and 2 yrs post index, ≥1 claim for DU or ≥60 days supply in every quarter during the 2-yr follow-up period, and ≥1 A1C result at both BL and 2 yrs were included. At BL, pts (N=872; 47.5% female) were (mean ± SD) 54.5 ± 8.2 yrs old with an A1C of 8.7 ± 1.8%. Antihyperglycemic medication use pre/post index included: insulin, 28%/35%; DPP-4 inhibitors, 37%/20%; SGLT2 inhibitors, 29%/44%. More than two-thirds were being treated for dyslipidemia, hypertension, or CVD. Key results are included in the Figure. Significant A1C reduction was observed from BL to 2 yrs (-1.3%, p Disclosure R. Mody: Employee; Self; Eli Lilly and Company. M. Yu: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; LifeLabs. Stock/Shareholder; Self; Eli Lilly and Company. M. Grabner: Research Support; Self; Eli Lilly and Company. K. Boye: Employee; Self; Lilly Diabetes. Stock/Shareholder; Self; Eli Lilly and Company. C. Teng: Research Support; Self; Eli Lilly and Company. A. Kwan: Employee; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company.

Purpose Due to the chronic and progressive nature of type 2 diabetes mellitus (T2DM), it is important to understand the long-term outcomes associated with antihyperglycemic medications. There are currently few long-term studies evaluating the real-world effectiveness of dulaglutide, a glucagon-like peptide-1 receptor agonist. The primary objective of this retrospective observational study was to evaluate glycemic control over a 24-month follow-up period among dulaglutide initiators with continuous treatment. The study used US claims data from the HealthCore Integrated Research Database between May 2014 and May 2019. Methods Patients were included if they were ≥18 years old with T2DM and had ≥1 pharmacy claim for dulaglutide during the index period between November 2014 and May 2017 (with index date = set as the earliest dulaglutide fill during index period), continuous enrollment in the 6 months' preindex and 24 months' postindex, ≥1 claim for dulaglutide or ≥60 days’ supply in every quarter during the 24-month follow-up period, and ≥1 glycosylated hemoglobin (HbA1c) result at both baseline and 24 months. Findings At baseline, 872 patients (47.5% female) had a mean (SD) age of 54.5 (8.2) years and an HbA1c value of 8.68% (1.8%) (71.36 [19.7] mmol/mol). More than two thirds were being treated for dyslipidemia, hypertension, or cardiovascular disease. A significant HbA1c reduction was observed from baseline to 24 months (−1.3% [–14.2 mmol/mol]; P Implications In this real-world study among dulaglutide initiators with continuous treatment, a clinically significant reduction in HbA1c value was seen at the 3-month assessment and persisted for up to 24 months. These data support the use of dulaglutide as an effective long-term treatment for T2DM in clinical practice.

Introduction The current literature of severe burns with autografting is scarce or limited to single data source. This study provides a wholistic view of the clinical and economic characteristics of the inpatient treatment of patients with burns using integrated medical chart abstraction with administrative claims. Methods Patients with thermal burns undergoing inpatient autografting between July 1, 2010 and November 30, 2019 were identified from large national health plans, representing over 50 million members in the US. The first observed hospitalization with autografting was regarded as the index event. Two hundred hospital patient medical records were abstracted for the clinical characteristics, using a standardized abstraction form, which were integrated with administrative data for economic characteristics. Those with large % TBSA were oversampled. Patients were stratified into three cohorts by %TBSA burned. A Bonferroni correction of alpha 0.017 was performed for post-hoc pairwise tests. Results Of 200 patients, 90 were categorized as low TBSA (< 10%), 75 moderate TBSA (10 – 24%), and 35 high TBSA (25+%). Overall, the high %TBSA cohort appeared to be younger, requiring more intensive care, and thereby incurring higher costs of care. The extent of some undocumented critical fields in the medical records was significant, for example (%undocumented): donor size (80%), BMI (31%), mesh ratio (30%), etc. 1 mean (SD) * compared with low TBSA, p< 0.017 Conclusions This study not only confirmed some conventional understanding of various TBSA cohorts, but also quantified their differences/similarities using multiple data sources. There was considerable incompleteness in many critical fields in the medical records, which limits the ability to generate broader insights. Despite the wide regard of medical records as a “gold standard” for outcomes analyses, future research should be aware of these limitations.

This paper provides empirical evidence and a behavioral explanation for the Chinese Lunar New Year (CLNY) effect and investigates whether the holiday effect weakens after market deregulation. Using emotion proxies from literature, we find that positive emotion plays an important role in contributing to higher returns surrounding the CLNY. We also show that the CLNY effect weakens when foreign investors’ participation increases, suggesting that the market deregulation may have contributed to this diminishing calendar anomaly.

This study investigates the impact of media exposure of corporate social irresponsibility (CSI) events on firm performances. Using unique data from an emerging market, we find that CSI events trigger significant and negative cumulative abnormal returns (CARs). Negative CARs are more profound for environment and safety issues as well as illegal violations. The existence of CSI events has negative impact on the subject firm's long-term operating and financial performances due to reputation damage and extra costs for regulatory compliance and rebuilding reputation. Furthermore, the number of CSI reports is negatively associated with firm performance and positively correlated with stock price crash risk. The negative effect is more profound for CSI events reported by the media than those self-reported by subject firms due to regulations. Our findings support the conjecture that media can serve as an external corporate governance mechanism, especially in emerging markets where well established governance structure is not yet available.

Objectives The purpose of this analysis was to assess the frequency of inadequate response (IR) over 1 year from advanced therapy (AT) initiation among ulcerative colitis (UC) patients in the United States using a claims-based algorithm. Baseline factors associated with IR to an AT were also analyzed. Methods This was a retrospective cohort study using claims data from the HealthCore Integrated Research Database (HIRD®). Adult patients with UC who initiated an AT (TNFi: adalimumab, golimumab, infliximab; non-TNFi: vedolizumab; other agent: tofacitinib) from 7/1/2016 to 8/31/2018 and had continuous enrollment ≥6 months before and ≥12 months after index date (date of first AT claim) were included. The index AT was defined as the first AT prescribed during the study time period. The claims-based algorithm used in this study to identify IR was originally developed and validated in rheumatoid arthritis1, and was modified for UC patients. Patients were identified as having IR to their index AT if during the 12 months after index date they had one or more of the following: low adherence (defined as proportion of days covered (PDC) Results A total of 1,692 UC patients were included in this analysis. Mean age was 42 years, 52% were male, 78% initiated a TNFi, and 22% initiated a non-TNFi as their index AT (Table 1). Over the 1-year follow-up period, 63% of UC patients had an IR to their AT: 42% of patients had low adherence, 24% switched/added a new AT, 18% added a new conventional therapy, 13% had a dose/frequency increase of their index AT, 14% had an addition/dose increase of oral glucocorticoids, 8% used a new pain medication, and 2% had surgery. Inadequate responders were more likely to be prescribed a TNFi (odds ratio (OR)=2.76; p

Objectives The purpose of this analysis was to assess the frequency of inadequate response (IR) over 1 year from biologic initiation among Crohn’s disease (CD) patients in the United States using a claims-based algorithm. Baseline factors associated with IR to a biologic were also analyzed. Methods This was a retrospective cohort study using claims data from the HealthCore Integrated Research Database. Adult patients with CD who initiated a biologic (TNFi: adalimumab, certolizumab, infliximab; non-TNFi: natalizumab, ustekinumab, and vedolizumab) from 7/1/2016 to 8/31/2018 and had continuous enrollment ≥6 months before and ≥12 months after index date (date of first biologic claim) were included. The index biologic was defined as the first biologic prescribed during the study time period. The claims-based algorithm used in this study to identify IR was originally developed and validated in rheumatoid arthritis and was modified for CD patients. Patients were identified as having IR to their index biologic if during the 12 months after index date they had one or more of the following: low adherence (defined as proportion of days covered (PDC) Results A total of 2,437 CD patients were included in this analysis. Mean age was 41 years, 53% were female, 81% initiated a TNFi, and 19% initiated a non-TNFi as their index biologic (Table 1). Over the 1-year follow-up period, 62% of CD patients had an IR to their biologic: 41% of patients had low adherence, 14% switched/added a new biologic, 13% added a new conventional therapy, 12% had a dose/frequency increase of their index biologic, 12% had an addition/dose increase of oral glucocorticoids, 8% used a new pain medication, and 5% had surgery. Inadequate responders were more likely to be female (odds ratio (OR)=1.36; p Conclusion Over 62% of CD patients had an inadequate response to their index biologic within 1 year after initiation, mostly driven by low adherence. This modified claims-based algorithm for CD appears useful to classify inadequate responders in health plan claims data. Additional research is needed to further validate this algorithm in a clinical setting.

The case–crossover (CCO) design was originally intended to study exposures characterized as intermittent with acute effects. The performance of the CCO design is not well characterized under alternative exposure and outcome relationships. The purpose of this study was to evaluate the ability of the CCO to identify simulated treatment effects under different drug exposures and outcomes relationships while varying the duration of the 1:1 matched risk and control windows. The simulated data were obtained from the Observational Medical Dataset Simulator, version 2 (OSIM2). The area under the receiver operator characteristic curve (AUC) was calculated to compare CCO performance across outcome types, simulated relative risk (RR), and duration of risk and control windows. The AUC for acute outcomes was higher for shorter risk and control windows and improved with higher simulated RR. For example, the AUC for the simulated RR of 4 was 0.95 for a 30-day window length and 0.78 for a 360-day window length. The AUC for the accumulative outcomes increased with longer risk and control windows and stronger simulated RR. For example, the AUC for the simulated RR of 4 was 0.85 for a 360-day window length and 0.23 for a 30-day window length. Risk and control window lengths did not appear to sufficiently alter the AUC for insidious onset outcomes. The CCO performed best for acute-onset outcomes, but may be useful for exploring adverse outcomes with accumulative effects. Careful consideration must be given to the hypothesized drug exposure and outcome distribution because specification of risk and control window duration affects CCO performance.

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.

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

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.

Introduction Autograft is considered the standard of care for severe burns; however, data on the economic outcomes in the pediatric population are sparse. This study assessed the healthcare resource utilization (HCRU) and costs of care among pediatric patients undergoing autografting for thermal burns. Methods The HealthCore Integrated Research Database was used to identify patients < 18 years old with thermal burns receiving the first inpatient autograft between 1/1/2011 and 6/30/2016. The first admission date was assigned as the index date; 12-month pre- and 24-month post-index-date continuous enrollment were required. Patient demographics, clinical characteristics, HCRU, and total costs were assessed. Results Of 65 identified patients, mean age was 7.2 years (standard deviation, SD=5.19), 46.2% were < 6 years old, and 69.2% were male. The majority of burn sites were in upper limbs (64.6%) and lower limbs (52.3%), followed by trunk (41.5%) and eye, face, head, and neck (24.6%). Over 80.0% of patients had third or deep third degree burns; 60% had total body surface area (TBSA) < 10% of any degree burn, and only a few patients (≤ 10) had TBSA ≥ 30%. The mean total all-cause cost in the one-year pre-index period was $14,359 (SD=$27,393), and $9,274 (SD=$25,694) of that cost were burn-related. The average length of stay of the index hospitalization was 10.9 days (SD=10.72), with mean total cost of $94,652 (SD=$162,176). The first-year post-index mean total cost was $111,536 (SD=$174,616) and 93.5% (including index hospitalization) were burn-related. On average, the index hospitalization accounted for 84.9% of the first-year costs. The second-year mean total cost was $10,734 (SD=$40,185), with 5.9% burn-related. Very few (≤ 10) patients had a burn-related hospitalization in the first year after discharge from the index hospitalization, and none had any burn-related inpatient stay in the second year. Conclusions The first-year economic burden after burn injury in this pediatric population was substantial, driven by the initial hospitalization for those undergoing autografting. Burn-related HCRU and cost reduced considerably in the second year post-index. Applicability of Research to Practice This study provided insights on the economic burden of pediatric patients with thermal burns who underwent inpatient autografting. Although autograft is part of the standard of care for severe burns, healthy skin availability and morbidity associated with skin harvest for autograft are major concerns among this vulnerable population. Innovations in burn care are warranted to ensure improved clinical and economic outcomes among patients with thermal burns.

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

According to the institution-based view of corporate governance, firm-governance efficiency is influenced by the institutional environment in which the firm operates. In this study, we examine how firms under a family-governance system adapted to institutional reforms over time. The results of the analysis indicate that institutional reforms reduce firm dependence on family governance and eliminate the negative effects on performance exerted by a controlling family’s pyramidal ownership structure. We also find that institutional reforms foster external corporate governance by domestic institutional investors. In conclusion, our study shows that institutional reforms alter the essence of family firm governance.

Objective.To compare survival in American veterans with and without the HLA-B27 (B27) gene.Methods.Mortality was evaluated in a national cohort of veterans with clinically available B27 test results between October 1, 1999, and December 31, 2011. The primary outcome was the mortality difference between B27-positive and B27-negative veterans, adjusted for age, sex, race, and diagnoses codes for diseases that may have influenced both B27 testing and mortality, including psoriasis, inflammatory bowel disease, spondyloarthritis (SpA), and other types of inflammatory arthritis. The secondary outcomes were the adjusted mortality HR for B27+ and B27− veterans, in subgroups with and without SpA.Results.Among veterans with available B27 test results, 27,652 (84.7%) were B27− and 4978 (15.3%) were B27+. The mean followup time was 4.6 years. Mortality was higher in the B27+ group than in the B27− group (HR 1.15, 95% CI 1.03–1.27). Mortality was also higher in the B27+ subgroups with SpA (HR 1.35, 95% CI 1.06–1.72) and without SpA (HR 1.11, 95% CI 0.99–1.24), but the difference was significant only in the subgroup with SpA.Conclusion.B27 positivity was associated with an increased mortality rate in a cohort of veterans clinically selected for B27 testing, after adjustment for SpA. In the subgroup with SpA, the mortality rate was associated with B27 positivity, and in the subgroup without SpA, there was a nonsignificant association between B27+ and mortality.

OBJECTIVE Combination treatments for patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX) alone include the addition of a tumor necrosis factor inhibitor (TNFi) or the addition of sulfasalazine (SSZ) and hydroxychloroquine to MTX (triple therapy). We compared persistence and adherence rates between these 2 combination therapies in US veterans and report the reasons for discontinuation of combination treatment in these groups. METHODS Using Veteran's Affairs clinical and administrative data from 2006 to 2012, veterans with RA escalating treatment from MTX to MTX-TNFi or triple therapy were examined for a 12-month period after combination initiation. Persistence was defined as treatment without a ≥90-day gap in therapy. Adherence was calculated using the proportion of days covered ≥80% at 12 months. Matching weights-adjusted models were applied to more closely mimic randomization in this study. The reasons that patients discontinued their combination regimens were identified by chart abstraction. RESULTS Full persistence at 1 year was 45% in the MTX-TNFi patients (n = 2,125) and 18% in the triple therapy patients (n = 171) (P < 0.001). Adherence was higher for the MTX-TNFi group (26%) than the triple therapy group (11%) (P < 0.0001). The triple therapy group was associated with significantly more treatment discontinuation, which was most often due to adverse drug events from SSZ. CONCLUSION Differences in persistence and adherence between the MTX-TNFi and triple therapy groups appear to be primarily related to adverse drug events that were most often attributed to SSZ.

Background There is interest in surrogate end points for clinical trials of chronic kidney disease progression because currently established end points—end-stage renal disease (ESRD) and doubling of serum creatinine level—are late events, requiring large clinical trials with long follow-up. Doubling of serum creatinine level is equivalent to a 57% decline in estimated glomerular filtration rate (eGFR). We evaluated type 1 error and required sample size for clinical trials using surrogate end points based on lesser eGFR declines. Study Design Simulation study. Setting & Participants Simulations evaluating 3,060 scenarios representative of 19 treatment comparisons in 13 chronic kidney disease clinical trials. Index Tests Surrogate end points defined as composite end points based on ESRD and either 30% or 40% eGFR declines. Reference Test Clinical outcome (ESRD) for type 1 error. Established end point (composite of ESRD and 57% eGFR decline) for required sample size. Results Use of the 40% versus 57% eGFR decline end point consistently led to a reduction in sample size > 20% while maintaining risk for type 1 error 2 ) for: (1) 2-, 3-, or 5-year trials with a high mean baseline eGFR (67.5mL/min/1.73m 2 ), and (2) 2-year trials with an intermediate mean baseline eGFR (42.5mL/min/1.73m 2 ). Use of the 30% versus the 40% eGFR decline end point often led to moderately larger reductions in sample size in the absence of an acute effect, but not in the presence of acute effects. Limitations The complexity of eGFR trajectories prevented evaluation of all scenarios for clinical trials. Conclusions Use of end points based on 30% or 40% eGFR declines is an appropriate strategy to reduce sample size in certain situations. However, risk for type 1 error is increased in the presence of acute effects, particularly for 30% eGFR declines. The decision to use these end points should be made after thorough evaluation of their expected performance under the conditions of specific clinical trials.

Purpose Outpatient infusions are commonly missing in Veterans Health Affairs (VHA) pharmacy dispensing data sets. Currently, Healthcare Common Procedure Coding System (HCPCS) codes are used to identify outpatient infusions, but concerns exist if they correctly capture all infusions and infusion-related data such as dose and date of administration. We developed natural language processing (NLP) software to extract infusion information from medical text infusion notes. The objective was to compare the sensitivity of three approaches to identify infliximab administration dates and infusion doses against a reference standard established from the Veterans Affairs rheumatoid arthritis (VARA) registry. Methods We compared the sensitivity and positive predictive value (PPV) of NLP to that of HCPCS codes in identifying the correct date and dose of infliximab infusions against a human extracted reference standard. Results The sensitivity was 0.606 (0.585-0.627) for HCPCS alone, 0.858 (0.842-0.873) for NLP alone, and 0.923 (0.911-0.934) for the two methods combined, with a PPV of 0.735 (0.716-0.754), 0.976 (0.969-0.983), and 0.957 (0.948-0.965) for each method, respectively. The mean dose of infliximab was 433mg in the reference standard, 337mg from HCPCS, 434mg from NLP, and 426mg from the combined method. Conclusions HCPCS codes alone are not sufficient to accurately identify infliximab infusion dates and doses in the VHA system. The use of NLP significantly improved the sensitivity and PPV for estimating infusion dates and doses, especially when combined with HCPCS codes. Copyright © 2014 John Wiley & Sons, Ltd. key words—natural language processing; Healthcare Common Procedure Coding System; computerized medical records systems; pharmacoepidemiology

Mechanically ventilated intensive care unit (ICU) patients are frequently managed using a continuous-infusion sedative. Although recent guidelines suggest avoiding benzodiazepines for sedation, this class of drugs is still widely used. There are limited data comparing sedative agents in terms of clinical outcomes in an ICU setting.Comparison of propofol to midazolam and lorazepam in adult ICU patients.Data were obtained from a multicenter ICU database (2003-2009). Patient selection criteria included age greater than or equal to 18 years, single ICU admission with single ventilation event (48 h), and treatment with continuously infused sedation (propofol, midazolam, or lorazepam). Propensity score analysis (1:1) was used and mortality measured. Cumulative incidence and competing risk methodology were used to examine time to ICU discharge and ventilator removal.There were 2,250 propofol-midazolam and 1,054 propofol-lorazepam matched patients. Hospital mortality was statistically lower in propofol-treated patients as compared with midazolam- or lorazepam-treated patients (risk ratio, 0.76; 95% confidence interval [CI], 0.69-0.82 and risk ratio, 0.78; 95% CI, 0.68-0.89, respectively). Competing risk analysis for 28-day ICU time period showed that propofol-treated patients had a statistically higher probability for ICU discharge (78.9% vs. 69.5%; 79.2% vs. 71.9%; P0.001) and earlier removal from the ventilator (84.4% vs. 75.1%; 84.3% vs. 78.8%; P0.001) when compared with midazolam- and lorazepam-treated patients, respectively.In this large, propensity-matched ICU population, patients treated with propofol had a reduced risk of mortality and had both an increased likelihood of earlier ICU discharge and earlier discontinuation of mechanical ventilation.

Introduction/Objective: Pulmonary function tests (PFTs) are objective estimates of lung function, but are not reliably stored within the Veteran Health Affairs data systems as structured data. The aim of this study was to validate the natural language processing (NLP) tool we developed—which extracts spirometric values and responses to bronchodilator administration—against expert review, and to estimate the number of additional spirometric tests identified beyond the structured data.Methods: All patients at seven Veteran Affairs Medical Centers with a diagnostic code for asthma Jan 1, 2006–Dec 31, 2012 were included. Evidence of spirometry with a bronchodilator challenge (BDC) was extracted from structured data as well as clinical documents. NLP’s performance was compared against a human reference standard using a random sample of 1,001 documents.Results: In the validation set NLP demonstrated a precision of 98.9 percent [d1] (95 percent confidence intervals (CI): 93.9 percent, 99.7 percent), recall of 97.8 percent (95 percent CI: 92.2 percent, 99.7 percent), and an F-measure of 98.3 percent for the forced vital capacity pre- and post pairs and precision of 100 percent (95 percent CI: 96.6 percent, 100 percent), recall of 100 percent (95 percent CI: 96.6 percent, 100 percent), and an F-measure of 100 percent for the forced expiratory volume in one second pre- and post pairs for bronchodilator administration. Application of the NLP increased the proportion identified with complete bronchodilator challenge by 25 percent.Discussion/Conclusion: This technology can improve identification of PFTs for epidemiologic research. Caution must be taken in assuming that a single domain of clinical data can completely capture the scope of a disease, treatment, or clinical test.Key words: asthma, bronchodilator challenge, natural language processing, pulmonary function

Large database research in axial spondyloarthritis (SpA) is limited by a lack of methods for identifying most types of axial SpA. Our objective was to develop methods for identifying axial SpA concepts in the free text of documents from electronic medical records.Veterans with documents in the national Veterans Health Administration Corporate Data Warehouse between January 1, 2005 and June 30, 2015 were included. Methods were developed for exploring, selecting, and extracting meaningful terms that were likely to represent axial SpA concepts. With annotation, clinical experts reviewed sections of text containing the meaningful terms (snippets) and classified the snippets according to whether or not they represented the intended axial SpA concept. With natural language processing (NLP) tools, computers were trained to replicate the clinical experts' snippet classifications.Three axial SpA concepts were selected by clinical experts, including sacroiliitis, terms including the prefix spond*, and HLA-B27 positivity (HLA-B27+). With supervised machine learning on annotated snippets, NLP models were developed with accuracies of 91.1% for sacroiliitis, 93.5% for spond*, and 97.2% for HLA-B27+. With independent validation, the accuracies were 92.0% for sacroiliitis, 91.0% for spond*, and 99.0% for HLA-B27+.We developed feasible and accurate methods for identifying axial SpA concepts in the free text of clinical notes. Additional research is required to determine combinations of concepts that will accurately identify axial SpA phenotypes. These novel methods will facilitate previously impractical observational research in axial SpA and may be applied to research with other diseases.

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.

To determine annual biologic drug and administration costs to the US Veterans Health Administration (VHA) per treated patient with rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who received abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab, or ustekinumab.Adults with at least one biologic claim between January 1, 2008 and December 31, 2011 were included. Evidence of enrollment in the VHA was required from 365 days before (pre-index) to 360 days after (post-index) the date of the first biologic claim (index date). Included patients had pre-index diagnoses of RA, PsO, PsA, and/or AS. Drug costs were from Federal Supply Schedule or 'Big Four' in November 2014. Administration costs were VHA fixed costs for infused ($169) and subcutaneous ($25) biologics.Of the 20,465 patients in the analysis, 10,711 received etanercept, 7838 received adalimumab, and 1196 received infliximab as the index biologic. In these patients, across all uses studied, the VHA incurred greater annual cost per treated patient for infliximab ($18,066) compared with adalimumab ($16,523) and etanercept ($16,526). In the first year post-index, ∼80% of patients were either persistent on these index biologics or re-started these index biologics after a ≥45-day treatment gap. Other biologics comprised5% of the study population, with sample sizes ranging from 3-374 patients each. Cost by indication for biologics used by20 patients ranged from $15,056 (etanercept) to $17,050 (abatacept) for RA; $16,697 (adalimumab) to $33,163 (ustekinumab) for PsO; $15,035 (etanercept) to $20,465 (infliximab) for PsA; and $14,239 (etanercept) to $18,536 (infliximab) for AS.The model was limited to the VHA. Results for biologics other than adalimumab, etanercept, and infliximab were difficult to interpret because of small sample sizes.Infliximab has higher cost to the VHA than adalimumab or etanercept.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most commonly used prescription and over-the-counter analgesic medications worldwide. NSAID toxicity, however, limits their use by raising cardio-renal morbidity and mortality risk. Withdrawal of the balancing vasodilatory

Outpatient infusions are commonly missing in Veterans Health Affairs (VHA) pharmacy dispensing data sets. Currently, Healthcare Common Procedure Coding System (HCPCS) codes are used to identify outpatient infusions, but concerns exist if they correctly capture all infusions and infusion-related data such as dose and date of administration. We developed natural language processing (NLP) software to extract infusion information from medical text infusion notes. The objective was to compare the sensitivity of three approaches to identify infliximab administration dates and infusion doses against a reference standard established from the Veterans Affairs rheumatoid arthritis (VARA) registry.We compared the sensitivity and positive predictive value (PPV) of NLP to that of HCPCS codes in identifying the correct date and dose of infliximab infusions against a human extracted reference standard.The sensitivity was 0.606 (0.585-0.627) for HCPCS alone, 0.858 (0.842-0.873) for NLP alone, and 0.923 (0.911-0.934) for the two methods combined, with a PPV of 0.735 (0.716-0.754), 0.976 (0.969-0.983), and 0.957 (0.948-0.965) for each method, respectively. The mean dose of infliximab was 433 mg in the reference standard, 337 mg from HCPCS, 434 mg from NLP, and 426 mg from the combined method.HCPCS codes alone are not sufficient to accurately identify infliximab infusion dates and doses in the VHA system. The use of NLP significantly improved the sensitivity and PPV for estimating infusion dates and doses, especially when combined with HCPCS codes.

Background The ability to assess rheumatoid arthritis (RA) disease activity using administrative data could provide a potential mechanism to identify patients with high disease activity who may be candidates for enhanced RA treatment. The Veterans Affairs rheumatoid arthritis (VARA) registry is a prospective observational cohort that collects RA disease activity measurements including the 28 joint count disease activity score (DAS28) at twelve US Veterans Affairs (VA) Medical Centers. Objectives This study used VA administrative data to develop a model to predict DAS28 in US Veterans. Results We identified 1,582 US Veterans with RA who fulfilled enrollment criteria. The average age was 62.7±11.0 years, 91% male, with a disease duration 13.7±12.1 years with 78% and 74% seropositive for rheumatoid factor and anti-CCP antibodies respectively. Of the 1,275 variables evaluated, 175 had prevalence of 1% or more for consideration in the model. Of these 175 candidate variables, 32 remained in the final model. The key variables associated with disease activity were related to number of clinic visits (rheumatology, primary care, and ancillary services), numbers of laboratory tests, medication changes, imaging episodes, and surgery. The association of the predicted and observed DAS28 was relatively limited with unadjusted and adjusted R-square as 0.24 and 0.22 respectively. The model was very sensitive for detection of high/moderate disease (sensitivity =91.3%) but the specificity was only 25.3%.US Veterans with RA enrolled in the VARA registry with administrative data available for the year prior to DAS28 measurement and were evaluated. Patients were excluded if they had cancer, organ transplantation, or other autoimmune diseases. We identified 1,275 administrative data elements with suspected association with disease activity to investigate for association with DAS28 score. Least absolute shrinkage and selection operator (LASSO) was used to develop a model for the prediction of DAS28 as a continuous variable. The sensitivity, specificity, positive and negative predictive values were calculated. For these calculations, we defined high/moderate disease as DAS28>3.2 and low disease as DAS28≤3.2 in a categorical manner. Conclusions While there were multiple administrative elements that correlated with disease activity measured by DAS28, it was not possible to develop a strong predictive model using available administrative data. These observations suggest that the continued direct observation of disease activity remains the most effective measure to identify RA patients with high disease activity. However the transient nature of RA disease activity may predicate the need to refine our model to account for disease duration. Additionally a single point-in-time measurement may not be indicative of patient disease activity over a long period of time. The development of other methods that can extract information from provider assessment of disease from electronic medical records has the potential to meet this critical need. 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, M. Trivedi Shareholder of: Amgen, Employee of: Amgen, B. Sauer Grant/research support from: Amgen

Background Epidemiologic research would be significantly enhanced if accurate and reliable methods were available to assess rheumatoid arthritis (RA) disease activity using administrative data. The VA rheumatoid arthritis (VARA) registry is a prospective observational cohort that collects RA disease activity including the 28 joint count disease activity score (DAS28) and clinical disease activity index (CDAI). VA administrative data are available and can be employed to develop models to estimate RA disease activity measured by DAS28 and CDAI. Objectives 1. Use administrative data to develop models that predict disease activity. 2. Assess the accuracy of the model under different conditions including defining administrative variables as continuous (CON) and/or categorical (CAT) and stratifying by different disease durations. 3. Describe the accuracy of the models for predicting disease activity for both DAS28 and CDAI. Methods US Veterans with RA enrolled in the VARA registry without cancer, organ transplantation, or other autoimmune diseases were included in the model if they were enrolled in VA with one year of administrative data available before the first DAS28. We identified 1,275 administrative data elements with suspected association with disease activity for prediction modeling. The least absolute shrinkage and selection operator (LASSO) was used for variable selection and model development. A series of LASSO models were developed that varied the input variables. Variables were required to have ≥1% prevalence in the cohort to be included in model selection. Sub-analysis was also performed in patients with ≤2 years and ≤5 years of disease duration. Results There were 1,582 US Veterans with RA who fulfilled enrollment criteria. The average age was 62.7±11.0 years, 91% male, with a disease duration 13.7±12.1 years with 78% and 74% seropositive for rheumatoid factor and anti-CCP antibodies respectively. The adjusted r-square for the six models tested ranged from 0.20–0.24 for DAS28 and 0.17 to 0.24 for CDAI. When stratified by disease duration, the r-square associations for patients with and without ≤2 and ≤5 years of RA duration were 0.29–0.31 versus 0.22–0.27 for DAS28 and CDAI respectively. Conclusions The multiple models tested yielded very similar results with limited association of predicted disease activity with actual measured disease activity by DAS28 and CDAI in VARA. The use of CON versus CAT variables, multiple definitions for disease activity, and limitation of disease duration to early RA did drastically affect prediction accuracy. Future research should investigate additional strategies to collect components of disease activity measures directly from medical records. Disclosure of Interest G. Cannon Grant/research support from: Amgen, C.-C. Teng: None declared, N. Accortt Shareholder of: Amgen, Employee of: Amgen, D. Collier Shareholder of: Amgen, Employee of: Amgen, M. Trivedi Shareholder of: Amgen, Employee of: Amgen, B. Sauer Grant/research support from: Amgen

Background A randomized controlled trial (RTC) including US veterans with rheumatoid arthritis (RA) reported similar clinical efficacy, persistence, and adherence in a comparison of combination therapy with triple therapy (methotrexate [MTX] + hydroxychloroquine [HCQ] + sulfasalazine [SSZ]) versus tumor necrosis factor inhibitor-methotrexate (TNFi-MTX).1 In contrast, an analysis of US clinical practice based on claims data for commercially insured patients reported differences in persistence and adherence between these combinations.2 Objectives To report one-year persistence and adherence of triple therapy and TNFi-MTX in US Veterans initiating combination therapy to allow preliminary comparison of findings in clinical practice and RCT-reported data. Methods US veterans with RA initiating TNFi-MTX or triple therapy between Jan 1, 2006 and Dec 31, 2012 after 6-months of VA enrollment without prior combination therapy were evaluated for 12-months. The index date for starting combination therapy was defined as the date on which the final drug to complete each treatment combination was initiated. Three different definitions for termination of combination therapy were defined and persistence over one year calculated for each method. Method #1: ≥45-day gap for the TNFi or two drugs in triple therapy, or initiation of a non-TNFi biologic or new conventional DMARD; method #2: Same as #1 except switch to another TNFi in TNFi+MTX group or change in conventional DMARD was allowed; method #3: ≥45-day gap in any drug of the combination or initiation of any new biologic or conventional DMARD. Persistence on individual drugs within each therapy was assessed and defined as no ≥45-day gap for that drug. Adherence was defined as Proportion of Days Covered (PDC)>80% and determined for each individual drug and the combination of all drugs. Results A total of 2,936 TNFi-MTX patients and 1,125 triple therapy patients met the eligibility criteria (mean [SD] age at index 60.7 [10.8] vs. 61.8 [9.9], 13.0% vs. 9.0% female, mean [SD] Charlson comorbidity index 1.61 [1.03] vs. 1.81 [1.36]). After 12 months, persistence in the TNFi-MTX arm was significantly greater across all three approaches (p Conclusions US Veterans initiating TNFi-MTX therapy consistently showed significantly greater persistence and adherence than those initiating triple therapy during clinical practice in contrast to similar persistence and adherence reported with these combinations in a clinical trial. References O9Dell et al. N Engl J Med 2013;369:307-318. Bonafede et al. Ann Rheum Dis 2014;73:Suppl 2;335. Acknowledgements Research funded by Immunex Corporation, a wholly owned subsidiary of Amgen Inc. Disclosure of Interest G. Cannon Grant/research support from: Amgen, C. C. Teng Grant/research support from: Amgen, D. Tang Shareholder of: Amgen, Employee of: Amgen, J. Leng Grant/research support from: Amgen, D. Harrison Shareholder of: Amgen, Employee of: Amgen, B. Sauer Grant/research support from: Amgen

Background Comparison of effectiveness of biologic disease modifying anti-rheumatic drugs (DMARDs) in clinical practice may provide important insight into their clinical benefit in patients with rheumatoid arthritis (RA). A recent validated algorithm is available to evaluate clinical effectiveness in US veterans. 1 Objectives To compare the effectiveness of abatacept (ABA), adalimumab (ADA), etanercept (ETN), infliximab (INF), and rituximab (RIT) in US veterans with RA and assess the reasons for failure. Methods National Veterans Affairs (VA) pharmacy and administrative databases were evaluated on all US veterans initiating biologics from Jan 1, 2008 to Jan 1, 2012 and followed until Jan 1, 2013 to allow ≥1-year of follow-up per patient. The analysis was limited to the first treatment course beginning ≥180 days after VA enrollment, consistent with a new biologic initiation and agents with ≥100 dispensing episodes. The validated effectiveness algorithm is based on administrative claims data. Medications were classified as effective if all of the following criteria were met: high adherence, Medication Possession Ratio (MPR) >80% for self-injected biologic or receiving at least 80% of the minimum recommended number of infusions, no biologic dose increase, no switching biologics, no new non-biologic disease modifying antirheumatic drugs (DMARD), 1 Results During the study period, 19,244 RA patients were treated with biologics; 9,979 had 1-year of follow-up and 4,704 patients had their first course beginning >180 days after VA enrollment. Conclusions Algorithm-defined effectiveness was higher for injectable tumor necrosis factor inhibitors (ADA, ETN) than for infused biologics, ABA, INF, and RIT. Major factors associated with lower effectiveness were low adherence and biologic dose escalation. References Curtis et al. Arthritis Res Ther, 2011, 13(5), R155. Acknowledgements Research funded by VA Research Program and Immunex Corporation, a wholly owned subsidiary of Amgen Inc., and by Wyeth, which was acquired by Pfizer Inc. in October 2009. Disclosure of Interest G. Cannon: None declared, T. He: None declared, C.-C. Teng: None declared, J. Leng: None declared, C.-C. Lu: None declared, D. Tang Shareholder of: Amgen, Employee of: Amgen, N. Shah Shareholder of: Amgen, Employee of: Amgen, D. Harrison Shareholder of: Amgen, Employee of: Amgen, B. Sauer: None declared DOI 10.1136/annrheumdis-2014-eular.1903