The occurrence of hyponatremia and its importance as a prognostic factor in a cross-section of cancer patients.

BACKGROUND: Hyponatremia is prognostic of higher mortality in some cancers but has not been well studied in others. We used a longitudinal design to determine the incidence and prognostic importance of euvolemic and hypervolemic hyponatremia in patients following diagnosis with lymphoma, breast (BC), colorectal (CRC), small cell lung (SCLC), or non-small cell lung cancer (NSCLC). METHODS: Medical record and tumor registry data from two large integrated delivery networks were combined for patients diagnosed with lymphoma, BC, CRC, or lung cancers (2002-2010) who had ≥1 administration of radiation/chemotherapy within 6 months of diagnosis and no evidence of hypovolemic hyponatremia. Hyponatremia incidence was measured per 1000 person-years (PY). Cox proportional hazard models assessed the prognostic value of hyponatremia as a time-varying covariate on overall survival (OS) and progression-free survival (PFS). RESULTS: Hyponatremia incidence (%, rate) was 76 % each, 1193 and 2311 per 1000 PY, among NSCLC and SCLC patients, respectively; 37 %, 169 in BC; 64 %, 637 in CRC, and 60 %, 395 in lymphoma. Hyponatremia was negatively associated with OS in BC (HR 3.7; P = <.01), CRC (HR 2.4; P < .01), lung cancer (HR 2.4; P < .01), and lymphoma (HR 4.5; P < .01). Hyponatremia was marginally associated with shorter PFS (HR 1.3, P = .07) across cancer types. CONCLUSIONS: The incidence of hyponatremia is higher than previously reported in lung cancer, is high in lymphoma, BC, and CRC and is a negative prognostic indicator for survival. Hyponatremia incidence in malignancy may be underestimated. The effects of hyponatremia correction on survival in cancer patients require further study.

Development and Validation of Algorithms to Identify Statin Intolerance in a US Administrative Database.

OBJECTIVES: To develop and validate algorithms to define statin intolerance (SI) in an administrative database using electronic medical records (EMRs) as the reference comparison. METHODS: One thousand adults with one or more qualifying changes in statin therapy and one or more previous diagnoses of hyperlipidemia, hypercholesterolemia, or mixed dyslipidemia were identified from the Henry Ford Health System administrative database. Data regarding statin utilization, comorbidities, and adverse effects were extracted from the administrative database and corresponding EMR. Patients were stratified by cardiovascular (CV) risk. SI was classified as absolute intolerance or titration intolerance on the basis of changes in statin utilization and/or the occurrence of adverse effects and laboratory testing for creatine kinase. Measures of concordance (Cohen's kappa [κ]) and accuracy (sensitivity, specificity, positive predictive value [PPV], and negative predictive value) were calculated for the administrative database algorithms. RESULTS: Half of the sample population was white, 52.9% were women, mean age was 60.6 years, and 35.7% were at high CV risk. SI was identified in 11.5% and 14.0%, absolute intolerance in 2.2% and 3.1%, and titration intolerance in 9.7% and 11.8% of the patients in the EMR and the administrative database, respectively. The algorithm identifying any SI had substantial concordance (κ = 0.66) and good sensitivity (78.1%), but modest PPV (64.0%). The titration intolerance algorithm performed better (κ = 0.74; sensitivity 85.4%; PPV 70.1%) than the absolute intolerance algorithm (κ = 0.40; sensitivity 50%; PPV 35.5%) and performed best in the high CV-risk group (n = 353), with robust concordance (κ = 0.73) and good sensitivity (80.9%) and PPV (75.3%). CONCLUSIONS: Conservative but comprehensive algorithms are available to identify SI in administrative databases for application in real-world research. These are the first validated algorithms for use in administrative databases available to decision makers.

A checklist for ascertaining study cohorts in oncology health services research using secondary data: report of the ISPOR oncology good outcomes research practices working group.

OBJECTIVES: The ISPOR Oncology Special Interest Group formed a working group at the end of 2010 to develop standards for conducting oncology health services research using secondary data. The first mission of the group was to develop a checklist focused on issues specific to selection of a sample of oncology patients using a secondary data source. METHODS: A systematic review of the published literature from 2006 to 2010 was conducted to characterize the use of secondary data sources in oncology and inform the leadership of the working group prior to the construction of the checklist. A draft checklist was subsequently presented to the ISPOR membership in 2011 with subsequent feedback from the larger Oncology Special Interest Group also incorporated into the final checklist. RESULTS: The checklist includes six elements: identification of the cancer to be studied, selection of an appropriate data source, evaluation of the applicability of published algorithms, development of custom algorithms (if needed), validation of the custom algorithm, and reporting and discussions of the ascertainment criteria. The checklist was intended to be applicable to various types of secondary data sources, including cancer registries, claims databases, electronic medical records, and others. CONCLUSIONS: This checklist makes two important contributions to oncology health services research. First, it can assist decision makers and reviewers in evaluating the quality of studies using secondary data. Second, it highlights methodological issues to be considered when researchers are constructing a study cohort from a secondary data source.

Incremental healthcare cost burden in patients with atrial flutter only.

Background: Limited information is available on the costs related to atrial flutter only. This study provides a comprehensive estimate of the cost in patients with atrial flutter only versus matched patients without any atrial arrhythmia. Methods: Patients over 20 years of age with a minimum of one inpatient or two outpatient diagnosis codes for atrial flutter in 2005 and a minimum of 12 months of continuous enrollment pre- and post-index were identified using the MarketScan Commercial and Medicare databases. Atrial flutter patients were propensity matched to patients without atrial arrhythmias. Total costs for each patient for 12 months post-index were calculated. National cost was estimated using the projected prevalence of atrial flutter for 2010. Results: A total of 1,042 patients with atrial flutter only were successfully matched with comparison patients. For atrial flutter patients compared to matched controls without atrial arrhythmias, total mean annual cost per patient was 81% higher ($23,008 vs. $12,717) and mean annual inpatient expenditure was 214% higher ($8,518 vs. $2,713). When applied to national atrial flutter prevalence data, total incremental cost burden was estimated to be $687.9 million per year more than patients without atrial arrhythmias, primarily due to cardiovascular specific expenditure ($377 million, 55% of total) with 58% ($218.5 million) of the increased inpatient expenditure due to cardiovascular specific admissions and $159 million (23%) for atrial flutter specific care. Sex-related differences were also present in atrial flutter only patients. Conclusion: Although atrial flutter-only patients are less prevalent than atrial fibrillation patients, the national incremental cost burden in atrial flutter is substantial on a per-patient level.

Hematologic outcomes and blood utilization in cancer patients with chemotherapy-induced anemia (CIA) pre- and post-national coverage determination (NCD): results from a multicenter chart review.

PURPOSE: In July 2007, the Centers for Medicare and Medicaid Services (CMS) limited coverage of erythropoiesis-stimulating agents (ESAs) in cancer patients with chemotherapy-induced anemia (CIA) through a National Coverage Determination (NCD). The primary objective of this study was to compare transfusion rates in patients with CIA with lung, breast, or colorectal cancer before and after the NCD. METHODS: Adult Medicare patients with CIA treated at 49 community oncology clinics were selected from two time periods based on clinics' NCD implementation date. Chart data were abstracted for 12 weeks post-CIA episode start, defined as hemoglobin (Hb) level <11 g/dL while receiving chemotherapy or within 60 days of the last chemotherapy dose. Multivariate analyses were used to calculate the odds of transfusion and to assess the units of blood transfused, controlling for differences in demographics, clinical history, and chemotherapy. RESULTS: Eight hundred pre-NCD and 994 post-NCD patients from 49 sites were selected. Of the patients, 56% used ESAs post-NCD vs. 88% pre-NCD (p < 0.0001). The duration of ESA use decreased in the post-NCD (32.1 days) vs. pre-NCD (48.4 days, p < 0.0001) group. The post-NCD group reported significantly lower Hb levels, higher odds of receiving a transfusion (odds ratio: 1.41, 95% CI 1.05-1.89, p = 0.0238) and increased blood utilization of 53% (units transfused: OR 1.53, 95% CI 1.15-2.04, p = 0.0034). CONCLUSIONS: Decreased frequency and duration of ESA administration were reported in the post-NCD vs. pre-NCD period. Findings were accompanied by a modest but statistically significant increase in transfusions and a decrease in Hb values.

Venous thromboembolism in the US: does race matter?

Studies investigating racial differences in the prevalence of venous thromboembolism (VTE) have generally been conducted on a limited scale. This analysis measured VTE prevalence across racial groups in a population of US Medicaid enrollees from 2002 to 2005. Records for patients aged ≥ 18 years with VTE between January 1, 2002 and December 31, 2005 were retrieved from the MarketScan® Multi-State Medicaid Database from Thomson Reuters. Patients were classified as having VTE in each calendar year by the presence of a VTE diagnosis on an inpatient claim or ≥ 1 outpatient claim with VTE diagnosis plus evidence of anticoagulant use. Patients dually eligible for Medicaid and Medicare were excluded. Logistic regression was used to calculate the odds of VTE. An average of 4.5 million Medicaid enrollees were study eligible in each calendar year, 72.2% of which had deep-vein thrombosis, 22.5% pulmonary embolism, and 5.3% had both. Patients were mainly Caucasian (46.8%), African-American (26.0%), and Hispanic (14.1%). VTE prevalence per 100,000 enrollees was highest in African-American males (584 in 2002-784 in 2005), followed by Caucasian males (457-643), Caucasian females (335-446), and African-American females (348-444). Hispanic males (94-149) and females (93-154) had lower prevalence of VTE. African-Americans had a significantly higher probability of having a VTE event than Caucasians (adjusted odds ratio 1.04, 95% confidence interval 1.00-1.07, P = 0.036). VTE prevalence increased over the study period and was highest in African-American males. More coordinated efforts are required to improve VTE awareness and prevention across all racial and ethnic groups.

Virologic Outcomes Among People Living With Human Immunodeficiency Virus With High Pretherapy Viral Load Burden Initiating on Common Core Agents.

BACKGROUND: People living with human immunodeficiency virus (PLWH) initiating antiretroviral therapy (ART) with viral loads (VLs) ≥100 000 copies/mL are less likely to achieve virologic success, but few studies have characterized real-world treatment outcomes. METHODS: ART-naive PLWH with VLs ≥100 000 copies/mL initiating dolutegravir (DTG), elvitegravir (EVG), raltegravir (RAL), or darunavir (DRV) between 12 August 2013 and 31 July 2017 were identified from the OPERA database. Virologic failure was defined as (i) 2 consecutive VLs ≥200 copies/mL after 36 weeks of ART; (ii) 1 VL ≥200 copies/mL with core agent discontinuation after 36 weeks; (iii) 2 consecutive VLs ≥200 copies/mL after suppression (≤50 copies/mL) before 36 weeks; or (iv) 1 VL ≥200 copies/mL with discontinuation after suppression before 36 weeks. Cox modeling estimated the association between regimen and virologic failure. RESULTS: There were 2038 ART-naive patients with high VL who initiated DTG (36%), EVG (46%), DRV (16%), or RAL (2%). Median follow-up was 18.1 (interquartile range, 12.4-28.9) months. EVG and DTG initiators were similar at baseline, but RAL initiators were older and more likely to be female with low CD4 cell counts while DRV initiators differed notably on factors associated with treatment failure. Virologic failure was experienced by 9.2% DTG, 13.2% EVG, 18.4% RAL, and 18.8% DRV initiators. Compared to DTG, the adjusted hazard ratio (95% confidence interval) was 1.46 (1.05-2.03) for EVG, 2.24 (1.50-3.34) for DRV, and 4.13 (1.85-9.24) for RAL. CONCLUSIONS: ART-naive PLWH with high VLs initiating on DTG were significantly less likely to experience virologic failure compared to EVG, RAL, and DRV initiators.Antiretroviral therapy-naïve people living with HIV (PLWH) initiating therapy with viral loads ≥100,000 copies/mL varied markedly at baseline. In adjusted models, PLWH initiating dolutegravir-based regimens were less likely to experience virologic failure as compared to elvitegravir, raltegravir and darunavir initiators.

Clinical and economic outcomes in patients at risk of venous thromboembolism receiving appropriate enoxaparin or unfractionated heparin prophylaxis.

Clinical and economic outcomes were compared following appropriate prophylaxis with enoxaparin or unfractionated heparin (UFH) in a large, real-world population of US hospitalised medical and surgical patients at risk of venous thromboembolism (VTE). Discharges from the Thomson Reuters MarketScan Hospital Drug Database (January 2004-March 2007) of patients aged > or =40 years, at risk of VTE according to the 7(th) American College of Chest Physicians (ACCP) guidelines, who spent > or =6 days in hospital and received appropriate ACCP-recommended enoxaparin or UFH prophylaxis were included. Patients with contraindications to anticoagulation were excluded. Hospital-acquired VTE, adverse events, and hospital costs for enoxaparin versus UFH were compared using univariate and multivariate analyses. Of the 5,136 discharges included, 4,014 (78%) received enoxaparin and 1,122 (22%) received UFH. Compared with UFH, enoxaparin was associated with significantly lower risk of hospital-acquired VTE (adjusted odds ratio [OR] 0.51, 95% confidence interval [CI] 0.30-0.86, p = 0.012), pulmonary embolism (adjusted OR 0.33, 95% CI 0.14-0.79, p = 0.013) or adverse events (adjusted OR 0.73, 95% CI 0.54-0.98, p = 0.034). Total hospital costs per discharge were lower for enoxaparin (US $16,865 +/- 10,979) than UFH (US $19,252 +/- 14,970), with a mean difference of US $2,388 in favour of enoxaparin (p < 0.001) (adjusted difference US $439, 95% CI US $ -39 to 909, p = 0.072). In patients at risk of VTE, appropriate enoxaparin prophylaxis was associated with a reduction in hospital-acquired VTE, adverse events, and costs compared with appropriate UFH prophylaxis. Increased appropriate use of enoxaparin in patients at risk of VTE may help to reduce the clinical and economic burden of this condition.

Healthcare expenditure and resource utilization in patients with anaemia and chronic kidney disease: a retrospective claims database analysis.

BACKGROUND/AIMS: We conducted a retrospective claims database analysis to examine the association of anaemia and anaemia management with healthcare expenditure and utilization in patients with chronic kidney disease (CKD) before the onset of dialysis. METHODS: Claims data on patients (aged > or =15 years) with CKD were collected from the Medstat Marketscan Commercial and Medicare Databases between 2000 and 2005. Using these data, patients were evaluated for anaemia of CKD, anaemia treatment status and healthcare costs and use. RESULTS: Of the 37,105 CKD patients, 9,807 (26%) had incident anaemia; 59% of these received at least one type of anaemia treatment, with 48% receiving an erythropoiesis-stimulating agent. The total adjusted per patient per month healthcare expenditure for all CKD patients was USD 2,749. Patients with anaemia had significantly greater overall expenditure, which was 38% higher than those without anaemia. Total expenditure was 17% higher for untreated versus treated anaemic patients, largely due to higher inpatient expenditure in the untreated cohort. CONCLUSION: This analysis suggests that the presence of anaemia is associated with greater medical expenditure in patients with CKD. However, we found that anaemia management may help to lower inpatient costs associated with anaemia in the CKD population.

Benchmarking HIV Quality Measures in the US OPERA HIV Cohort.

BACKGROUND: Quality measures are effective tools to improve patient outreach, retention in care, adherence, and outcomes. This study benchmarks National Quality Forum-endorsed HIV quality measures in a US clinical cohort. METHODS: This observational study utilized prospectively captured data from the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) database over 2014-2016 to assess quality measure achievement among patients with HIV in terms of medical visit frequency (#2079), medical visit gaps (#2080), viral suppression (#2082), and antiretroviral therapy (ART) prescriptions (#2083). The proportion of patients meeting each measure was calculated. Generalized estimating equations assessed trends in measure achievement. RESULTS: The OPERA sample included 23 059-42 285 patients with similar demographics and characteristics across measurement periods. Overall, 62%-66% of patients met the visit frequency measure (#2079), 81%-85% had no gaps between visits (#2080), 71%-73% achieved viral suppression (#2082), and 92%-94% were prescribed ART (#2083). The adjusted odds of achieving viral suppression and being prescribed ART increased over time by 3% and 19%, respectively, despite a significant decline in patient engagement (16% for #2079, 25% for #2080). Patients <30 years of age were significantly less likely to meet all measures than older patients (P < .0001), with particularly low levels of engagement. Measure achievement also varied by gender, ethnicity, region, and select clinical characteristics. CONCLUSIONS: Despite gains in the rate of ART prescription and viral suppression, there remains room for improvement in the care of patients with HIV. Strategies for quality improvement may be more effective if tailored by age group.

Patterns of bisphosphonate use in the United States in the treatment of metastatic bone disease.

PURPOSE: The purpose of this study was to determine the incidence of metastatic bone disease (MBD), the frequency of intravenous (I.V.) bisphosphonate use and its impact on skeletal-related events (SREs), and opioid use. PATIENTS AND METHODS: Patients diagnosed with MBD between 2000 and 2004 were identified using 2 Thomson MarketScan Research Databases. A total of 6783 patients, 1431 with breast cancer, fulfilled the criteria. Pain was assessed as the number of days on opioids, the strength of which was categorized according to the World Health Organization 3-step ladder for pain. RESULTS: Use of I.V. bisphosphonates steadily increased for all cancers from 17% in 2000 to 38% in 2004. For all patients, 61% received mild opioids and 35% received moderate to severe opioids at baseline. Use of I.V. bisphosphonates within the first 90 days after diagnosis of MBD was associated with a 63% decrease in SREs and reduction in use of moderate to severe opioids. Among patients with breast cancer, 10.6% received oral bisphosphonates before diagnosis of MBD, and 33.8% had pain at baseline. There was a 5.4% reduction in the use of moderate to severe opioids. CONCLUSION: Our data support the role of I.V. bisphosphonates in decreasing SRE and improving the quality of life for patients with MBD; the result is less pain and fewer SREs. More than 73% of all patients and 53% of patients with breast cancer never receive I.V. bisphosphonate treatment. Educational measures are warranted to increase the awareness by patients and physicians of the value of I.V. bisphosphonates in MBD.

Major Cardiovascular Events in Patients with Gout and Associated Cardiovascular Disease or Heart Failure and Chronic Kidney Disease Initiating a Xanthine Oxidase Inhibitor.

BACKGROUND: Several observational studies and meta-analyses have suggested that treating hyperuricemia in patients with gout and moderate or severe chronic kidney disease (CKD) may improve renal and cardiovascular (CV) outcomes. OBJECTIVE: To evaluate the impact of initiating allopurinol or febuxostat treatment on major CV events in patients with gout, preexisting CV disease (CVD) or heart failure (HF), and stage 3 or 4 CKD in a real-world setting. METHODS: Patients with gout (aged >18 years) who initiated allopurinol or febuxostat treatment between 2009 and 2013 after a diagnosis of stage 3 or 4 CKD and CVD-including coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease (PVD)-or HF were selected from the MarketScan databases. The major CV events included CAD-specific, cerebrovascular disease-specific, and PVD-specific events. Cox proportional hazards modeling identified the predictors of major CV events in aggregate, and of CAD, cerebrovascular disease, and PVD events, individually. RESULTS: During follow-up, 2426 patients (370 receiving febuxostat and 2056 receiving allopurinol; 63% male; mean age, 73 years) had 162 major CV events (3.8% in those receiving febuxostat vs 7.2% in those receiving allopurinol; P = .015). The rates of major CV events per 1000 person-years were 51.8 (95% confidence interval [CI], 28-87) in patients initiating febuxostat and 99.3 (95% CI, 84-117) among those initiating allopurinol. Overall, 49.4% of patients had a CAD event, 32.5% had a PVD event, and 23.5% had a cerebrovascular disease-specific event. Febuxostat initiation was associated with a significantly lower risk for a major CV event versus patients who initiated allopurinol (hazard ratio, 0.52; P = .02), driven in large part by lower PVD-specific events (P = .026). CONCLUSION: Patients with moderate-to-severe CKD and CVD or HF who initiated febuxostat treatment had a significantly lower rate of major CV events than patients who initiated allopurinol.

Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to-Severe Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for developing gout and having refractory disease. Gout flare prevention relies heavily on urate-lowering therapies such as allopurinol and febuxostat, but clinical decision making in patients with moderate-to-severe CKD is complicated by significant comorbidity and the scarcity of real-world cost-effectiveness studies. OBJECTIVE: To compare total and disease-specific health care expenditures by line of therapy in allopurinol and febuxostat initiators after diagnosis with gout and moderate-to-severe CKD. METHODS: A retrospective observational cohort study was conducted to compare mean monthly health care cost (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated allopurinol or febuxostat. The primary outcome was total mean monthly health care expenditures, and the secondary outcome was disease-specific (gout, diabetes, renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM 274.xx) aged ≥ 18 years with concurrent CKD (stage 3 or 4) were selected from the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat initiation. Patients were followed until disenrollment, discontinuation of the qualifying study agent, or use of the alternate study agent. Patients initiating allopurinol were subsequently propensity score-matched (1:1) to patients initiating febuxostat. Five generalized linear models (GLMs) were developed, each controlling for propensity score, to identify the incremental costs (vs. allopurinol) associated with febuxostat initiation in first-line (without prior allopurinol exposure) and second-line (with prior allopurinol exposure) settings. RESULTS: Propensity score matching yielded 2 cohorts, each with 1,486 patients (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was well balanced on numerous comorbidities and medication exposures with the following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients. CONCLUSIONS: Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur. DISCLOSURES: No outside funding supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A. Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time of this study. Tidwell and Schulman are employees of Outcomes Research Solutions, consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the design of the study and to the writing and review of the manuscript. All authors read and approved the final manuscript. Tidwell and Schulman collected the data, and all authors participated in data interpretation.

Incidence and complications of interstitial lung disease in users of tocilizumab, rituximab, abatacept and anti-tumor necrosis factor α agents, a retrospective cohort study.

INTRODUCTION: Interstitial lung disease (ILD) is a common extra-articular condition in rheumatoid arthritis (RA), but few studies have systematically investigated its incidence and risk factors in patients receiving anti-tumor necrosis factor-alpha (anti-TNFα) agents or alternate mechanisms of action (MOAs) (e.g., T-cell, B-cell, and interleukin-6 inhibitors). METHODS: RA patients at least 18 years old were selected from the MarketScan databases (2010-2012) if they had at least one prescription/administration of abatacept, rituximab, tocilizumab, or anti-TNF after having discontinued a different biologic agent and meeting enrollment criteria. Cox models estimated the risk of incident ILD and ILD-related hospitalization. Sensitivity analyses used an alternate ILD case definition. RESULTS: We identified 13,795 episodes of biologic exposure in 11,219 patients. Mean (standard deviation) follow-up was 0.7 (0.5) years. Patients receiving alternate MOA agents were more likely to have had recent exposure to steroids, prior exposure to a greater number of biologics, and history of ILD, anemia, chronic obstructive pulmonary disease, and other pulmonary conditions. When the sensitive definition was used, unadjusted ILD incidence rates (95% confidence interval, or CI) ranged from 4.0 (1.6-8.2, abatacept) to 12.2 (5.6-23.2, infliximab) per 1000 person-years. Being older (hazard ratio (HR) 3.5; 95% CI 2.1-6.0), being male (HR 3.1; 95% CI 1.2-8.4), and having another pulmonary condition (HR 4.8; 95% CI 1.7-13.7) were associated with increased ILD incidence in either sensitive and/or specific models. There were no significant differences by biologic class. Hospitalization rates (95% CI) when the sensitive definition was used ranged from 55.6 (6.7-200.7, tocilizumab) to 262.5 (71.5-672.2, infliximab). In Cox models, recent methotrexate exposure was associated with reduced ILD hospitalization (HR 0.16; 95% CI 0.06-0.46), whereas being male (HR 2.5; 95% CI 1.3-4.8) and having had a hospitalization for asthma (HR 3.4; 95% CI 1.2-9.8) or ILD/pneumonia (HR 2.3; 95% CI 1.1-4.7) in the 12 months prior to index were associated with increased hospitalization risk. CONCLUSIONS: There were no significant differences in the risk of ILD and its related complications between RA patients receiving anti-TNFα agents and those receiving alternate MOA agents. Further studies are needed that account for differences in baseline characteristics in order to fully evaluate the risk of ILD and its complications.

Factors associated with gastrointestinal perforation in a cohort of patients with rheumatoid arthritis.

OBJECTIVE: To estimate the incidence and risk factors for gastrointestinal (GI) perforation among patients with rheumatoid arthritis (RA). METHODS: Claims from employer health insurance plans were used to identify RA patients and those hospitalized for upper or lower GI perforation. GI perforation cases were identified using both a sensitive and a specific definition. A Cox model using fixed and time-varying covariates was used to evaluate the risk of GI perforation. RESULTS: Among 143,433 RA patients, and using a maximally sensitive GI perforation definition, 696 hospitalizations with perforation were identified. The rate of perforation was 1.70 per 1,000 person years (PYs; 95% confidence interval [95% CI] 1.58-1.83), and most perforations (83%) occurred in the lower GI tract. The rate of perforation was lower when a more specific GI perforation definition was used (0.87; 95% CI 0.78-0.96 per 1,000 PYs). Age and diverticulitis were among the strongest risk factors for perforation (diverticulitis hazard ratio [HR] 14.5 [95% CI 11.8-17.7] for the more sensitive definition, HR 3.9 [95% CI 2.5-5.9] for the more specific definition). Among various RA medication groups and compared to methotrexate, the risk of GI perforation was highest among patients with exposure to nonsteroidal antiinflammatory drugs (NSAIDs), concomitant nonbiologic disease-modifying antirheumatic drugs, and glucocorticoids. Biologic agents without glucocorticoid exposure were not a risk factor for perforation. CONCLUSION: GI perforation is a rare but serious condition that affects patients with RA, most frequently in the lower GI tract. Clinicians should be aware of risk factors for GI perforation when managing RA patients, including age, history of diverticulitis, and use of glucocorticoids or NSAIDs.

Estimation of total incremental health care costs in patients with atrial fibrillation in the United States.

BACKGROUND: Detailed information on the cost burden of atrial fibrillation (AF) is limited. To provide an up-to-date estimate of the national cost of AF, we conducted a retrospective, observational cohort study using administrative claims from the MarketScan Commercial and Medicare Supplemental research data bases, 2004 to 2006. METHODS AND RESULTS: Patients aged ≥20 years with ≥1 inpatient or ≥2 outpatient AF diagnoses in 2005 (first diagnosis=index) and ≥12 months' enrollment before and after index were selected. AF patients were propensity score-matched (1:1) with non-AF control subjects. Medical costs (2008 US$), including AF costs, other cardiovascular, and noncardiovascular costs, were examined over 1 year after index. National incremental costs of AF were based on age-/sex-specific AF prevalence projections for 2010. In total, 89 066 AF patients were matched to non-AF control subjects. Over 1 year, 37.5% of AF versus 17.5% of control subjects were hospitalized and 2.1% versus 0.1% died during hospitalization. For AF versus control subjects, mean annual inpatient costs per patient were $7841 versus $2622 (incremental cost, $5218), outpatient medical costs were $9225 versus $5629 ($3596), and outpatient pharmacy costs were $3605 versus $3714 (-$109) (all P<0.001). The total incremental cost of AF was $8705 per patient. The national incremental cost of AF was $26.0 billion (AF, $6.0 billion; other cardiovascular, $9.9 billion; noncardiovascular, $10.1 billion). Cardiovascular costs were based on claims with a primary disease diagnosis and may be underestimates. CONCLUSIONS: On the basis of current US age- and sex-specific prevalence data, the national incremental AF cost is estimated to range from $6.0 to $26.0 billion.

Cost comparison of capecitabine in patients with breast cancer.

OBJECTIVE: Capecitabine may have a higher acquisition cost compared with other select chemotherapy agents; however, its use is not associated with many of the costs typically encountered with intravenous chemotherapy, such as costs incurred through administration procedures and the management of subsequent tolerability issues. This study compared the cost of capecitabine- and taxane-based regimens in the treatment of breast cancer. STUDY DESIGN: Thomson Reuters MarketScan, a US employer claims database, was used to identify patients with a breast cancer diagnosis between 2000 and 2005 and at least one chemotherapy claim or hormone treatment in 2004 or 2005. METHODS: Cost data for treatment administration and management of selected chemotherapy-related adverse events were collected. Multivariate analyses were performed to adjust for differences in patient demographic and clinical factors. RESULTS: A total of 3630 patients were included in this analysis; 4216 treatment episodes were recorded. Mean unadjusted total monthly expenditures were lowest for capecitabine regimens compared with taxane plus anthracycline or other taxane regimens ($8445 vs. $13,295 and $12,323, respectively; P < 0.0001). The adjusted total monthly cost for capecitabine regimens was lower than the cost for taxane plus anthracycline regimen ($10,895 vs. $13,115) and other taxane regimens ($9253 vs. $12,116). Adjusted complication costs for taxane treatment episodes were almost double than those seen with capecitabine ($5509 for anthracycline plus taxane vs. $2940, and $3829 for other taxane regimens vs. $1750). CONCLUSIONS: Lower complication-related expenditures with capecitabine therapy accounted for majority of the cost differential seen in comparison with taxane-based therapy.

Patients with locally advanced and metastatic colorectal cancer treated with capecitabine versus 5-fluorouracil as monotherapy or combination therapy with oxaliplatin: a cost comparison.

INTRODUCTION: This study quantified the costs associated with the acquisition of chemotherapy, its administration, and the management of chemotherapy-related complications, and their effect on total patient expenditures. PATIENTS AND METHODS: Patients with locally advanced and metastatic colorectal cancer treated with capecitabine or 5-fluorouracil/leucovorin (5-FU/LV) as monotherapy or combination therapy with oxaliplatin from 2003-2006 were identified in the Thomson Reuters MarketScan® databases. Selection bias between treatment groups was addressed by propensity score matching, assessment of the risk of complications using Cox models, and an estimate of expenditures using general linear models. RESULTS: In respect to monotherapy, capecitabine users (n = 1272) were propensity score matched to 5-FU/LV users on a 1:1 ratio. The adjusted mean monthly cost was significantly lower for patients treated with capecitabine versus 5-FU/LV ($6683 vs. $9304, respectively; P < .0001). Although the cost of drug acquisition was significantly higher for capecitabine than for 5-FU/LV (unadjusted P < .0001), significantly lower costs of capecitabine administration (unadjusted P < .0001) and management of complications (adjusted costs, P < .0001) offset the difference, and drove a lower overall cost. In regard to combination therapy, capecitabine/oxaliplatin users (n = 263) were propensity score matched to 5-FU/LV/oxaliplatin users (n = 526) on a 1:2 ratio. The adjusted mean monthly cost was significantly lower for capecitabine/oxaliplatin than for 5-FU/LV/oxaliplatin ($11,436 vs. $14,320, respectively; P < .0001). The cost difference was driven by the significantly lower administration costs of capecitabine-based chemotherapy (unadjusted P < .0001) and management of complications (adjusted P < .0001). CONCLUSION: The monthly cost per patient during capecitabine or capecitabine/oxaliplatin treatment is significantly lower than during 5-FU/LV or 5-FU/LV/oxaliplatin treatment because of lower costs for the administration of chemotherapy and for the management of complications.

Cost burden of cardiovascular hospitalization and mortality in ATHENA-like patients with atrial fibrillation/atrial flutter in the United States.

BACKGROUND: The ATHENA trial (A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter) demonstrated that dronedarone reduced the risk of cardiovascular (CV) hospitalization/death by 24% (P < 0.001) in patients with atrial fibrillation (AF) and atrial flutter (AFL). HYPOTHESIS: In order to estimate the cost savings associated with dronedarone use, we estimated the costs associated with CV hospitalizations and inpatient mortality in a large cohort of ATHENA-like patients. METHODS: In this retrospective analysis, we evaluated the cost of CV hospitalization/mortality in real-world ATHENA-like patients without heart failure and with employer-sponsored Medicare supplemental insurance in the United States. Patients similar to those in ATHENA (age > or = 70 years with AF/AFL and > or = 1 stroke risk factor, without heart failure) who were hospitalized between January 2, 2005, and January 1, 2007, were identified from the MarketScan databases from Thomson Reuters. Health care costs were evaluated during the 12 months following the index hospitalization. RESULTS: The analysis included 10 200 ATHENA-like patients. Hospitalization for CV causes occurred in 53.9% of patients, with a total of 6700 CV hospitalizations for fatal/nonfatal causes. The most common nonfatal causes of CV hospitalizations were AF/other supraventricular rhythm disorders (20.2% of all CV hospitalizations), congestive heart failure (CHF; 14.3%), and transient ischemic attack (TIA)/stroke (10.7%). Mean costs per CV hospitalization for nonfatal causes were $10,908. Inpatient deaths from CV causes occurred in 264 (2.6%) patients; the most common causes of CV inpatient death were intracranial/gastrointestinal hemorrhage (24.2% of CV deaths), TIA/stroke (17.0%), and CHF (15.9%). Mean hospitalization costs per CV inpatient death were $18,565. CONCLUSIONS: Health care costs associated with CV hospitalizations and inpatient deaths among ATHENA-like patients in the US are high. Novel antiarrhythmic therapies such as dronedarone, with the potential to reduce CV hospitalizations/mortality in similar patients, could decrease health care costs if adopted in clinical practice.

Costs associated with complications are lower with capecitabine than with 5-fluorouracil in patients with colorectal cancer.

BACKGROUND: Capecitabine, an oral alternative to 5-fluorouracil (5-FU) in patients with colorectal cancer (CRC), has equal clinical efficacy and a favorable safety profile; however, its use may be limited because of unit cost concerns. In this study, the authors measured the cost of chemotherapy-related complications during treatment with capecitabine- and 5-FU-based regimens. METHODS: Patients with CRC who received at least 1 administration of capecitabine or 5-FU during 2004 and 2005 were identified from the Thomson MarketScan research databases. Monthly frequency and cost for 23 complications were recorded. Logistic regression was used to predict complication probability. General linear models were used to predict monthly complication cost and total monthly expenditure. RESULTS: In total, 4973 patients with CRC met the inclusion criteria for this analysis. Although the most frequently observed complications were the same between capecitabine and 5-FU (nausea and vomiting, infection, anemia, neutropenia, diarrhea), each was observed with greater frequency in 5-FU-based regimens. The mean predicted monthly complication cost was significantly higher (by 136%) with 5-FU monotherapy than with capecitabine monotherapy (difference, $601; 95% confidence interval [95% CI], $469-$737). In addition, the mean predicted monthly complication cost for 5-FU+oxaliplatin was higher than the cost with capecitabine plus oxaliplatin (difference, $1165; 95% CI, $892-$1595). When acquisition, administration, and complication costs were taken into consideration, there were no significant differences in the total cost between capecitabine regimens and 5-FU regimens. CONCLUSIONS: Capecitabine compared well with 5-FU-based therapy in patients with CRC and was associated with lower complication rates and associated costs.