A longitudinal analysis of costs associated with change in disease activity in systemic lupus erythematosus.

OBJECTIVES: To estimate the economic consequences of changes in disease activity on healthcare resource utilization (HRU) and costs. METHODS: A retrospective longitudinal study of systemic lupus erythematosus (SLE) patients receiving care in a regional integrated health delivery system in the US from 01/2004 through 03/2011 was conducted using electronic health records, medical chart reviews, and claims. Eligible patients were ≥18 years old, with ≥1 rheumatologist-confirmed SLE diagnosis and ≥1 eligible rheumatology encounter. Patients were continuously enrolled ≥90 days before and ≥30 days after the encounters. Charts were manually reviewed to estimate SLEDAI scores. Average unit costs of each medical procedure, facility use, and prescription were estimated from a payer perspective (2011 USD) using a managed care claims database. HRU and costs were calculated for the 30-day period surrounding every SLEDAI score date (10 days before and 19 after). Relationships between HRU/costs and SLEDAI scores were estimated using mixed-effect models. RESULTS: Overall, 178 SLE patients were included; mean age was 50.6 years, 91% were female, and 95.5% Caucasian. Patients had a total of 1343 encounters with SLEDAI scores over an average period of 1035 days. Reductions of SLEDAI scores were associated with reductions in HRU and costs. SLEDAI score reductions of 4-points were associated with reductions of 10% HRU and 14% costs over a 30-day period; reductions of 8-points had associated reductions of 19% HRU and 26% costs; and reductions of 10-points had associated reductions of 23% HRU and 31% costs. Annualized, changes in SLEDAI scores are associated with changes of $2485 (SLEDAI score change: 10-6), $4624 (10-2), and $5579 (10-0), respectively. CONCLUSION: Reductions in disease activity were associated with substantial reductions of HRU and costs. LIMITATIONS: Only short-term effects of disease activity change were investigated, disregarding other potential benefits of low disease activity on long-term organ damage prevention or comorbidities.

Outcomes in atrial fibrillation patients on combined warfarin & antiarrhythmic therapy.

BACKGROUND: This retrospective cohort study compared rates of treatment persistence, incidences of de novo stroke, arterial embolism, and hemorrhage/bleeding, and healthcare resource use and costs between atrial fibrillation/flutter (AF/AFL) patients receiving concomitant warfarin (W)+amiodarone (A) or warfarin+other antiarrhythmic drug (OAAD) therapy in real-world practice. METHODS: The Ingenix IMPACT database (1997-2009) was used to identify patients with ≥ 1 diagnostic claim for AF/AFL and concurrent pharmacy claims (≥ 60 days' supply) for W and A (n=4238) or W+OAAD (n=6332) within the first 90 days of initiating therapy. Outcomes of interest were assessed over 12 months following initiation of dual therapy. RESULTS: The W+A cohort was older than the W+OAAD cohort (mean 66.5 vs. 61.9 years) and had greater baseline comorbidity. The W+A cohort had significantly 1) lower rates of treatment persistence; 2) higher incidences of de novo stroke (hazard ratio [HR] 1.24), arterial embolism (HR 1.48) and combined stroke/hemorrhage/bleeding/arterial embolism (HR 1.25); 3) more frequent inpatient (incidence rate ratio [IRR] 1.25), emergency room (IRR 1.16) and outpatient (IRR 1.07) admissions; and 4) higher incidences of cardiovascular- (IRR 1.35) and arterial embolism- (IRR 1.94) related healthcare use than the W+OAAD cohort. Incremental total healthcare costs over 12 months were $4114 ($2397 inpatient; $1171 outpatient). CONCLUSIONS: Allowing for differences in prescribing practice, AF/AFL patients treated with W+A are at higher risk of stroke and arterial embolism, and have higher healthcare use and costs, than patients receiving W+OAAD.

Monitoring and switching patterns of patients with chronic myeloid leukemia treated with imatinib in community settings: a chart review analysis.

OBJECTIVES: Monitoring treatment response is an integral part of chronic myeloid leukemia (CML) treatment. The guidelines recommend regular monitoring using standard methods (e.g., real-time quantitative polymerase chain reaction based on the international scale for molecular response) and treatment adjustment when failure is detected among patients treated with imatinib. The objective of this study was to assess the real-world monitoring and therapy adjustment in this patient population in the US. METHODS: Twenty-nine physicians from community practices across the US participated in an online chart review. Adult patients with chronic phase CML who initiated imatinib as first-line therapy during 2006-2010 were selected. Information was collected up to 36 months after imatinib initiation, including response monitoring, response status, and therapy adjustment upon treatment failure. RESULTS: The study included 297 eligible patients. By 18 months, 47% of patients had received cytogenetic response assessment continuously as recommended by the guidelines. The corresponding proportion was 39% for continuous molecular response assessment. Among patients who experienced treatment failure by 18 months, only 14%-38% of patients switched to a second-generation tyrosine kinase inhibitor as recommended by the National Comprehensive Cancer Network and the European Leukemia Net guidelines. LIMITATIONS: Major limitations included limited generalizability and the inability to accurately assess molecular response due to the variations in testing methods during the study period. CONCLUSIONS: Based on the guidelines, the rates of treatment monitoring and switching upon failure were low, demonstrating the need for improvement in CML care in community settings in the US.

Treatment patterns and economic burden of metastatic and recurrent locally-advanced head and neck cancer patients.

OBJECTIVE: To characterize treatment patterns and measure the economic burden associated with metastatic (mHNC) and recurrent, locally-advanced head and neck cancer (rHNC). METHODS: Administrative claims from Medicare- and privately-insured individuals during 2004-2008 were used in this retrospective database study of patients with advanced HNC. Patients diagnosed with HNC were matched 1:1 to cancer-free controls to measure the incremental economic burden of HNC. Outcomes of interest were measured during the 6 months following the date of a secondary tumor diagnosis for metastatic patients or the date of a diagnosis indicating rHNC. To assess treatment patterns, HNC patients were evaluated for the use frequency of treatments (radiotherapy, chemotherapy and surgery). Costs were reported in 2008 US$ from a third-party payer perspective and were analyzed using generalized linear models and two-part regression models adjusting for differences in age and baseline Charlson Comorbidity Index (excluding cancer diagnoses) between the HNC and control cohorts. Components of cost included inpatient, outpatient and other medical services as well as pharmacy costs. RESULTS: The mHNC cohort consisted of 1042 patients and the rHNC cohort included 324 patients. The most common treatments for mHNC patients were supportive care (90.2%), radiation therapy (48.5%), surgery (41.9%) and chemotherapy (38.3%). Patients with rHNC frequently received HNC-related supportive care (71.0%), radiation therapy (67.9%) and chemotherapy (27.2%); HNC-related surgery was infrequent (12.7%) during the study period. The 6-month incremental adjusted total costs were $60,414 per patient for mHNC and $21,141 per patient for rHNC (p<0.0001). Approximately 46-58% of the incremental cost was attributable to outpatient visits, 27-37% to inpatient costs and 11-13% to pharmacy, depending on the HNC cohort. LIMITATIONS: The identification of mHNC/rHNC was based on diagnosis codes and treatment patterns with the limitation of the claims database. CONCLUSIONS: Metastatic and recurrent, locally-advanced HNC patients frequently receive cancer-related treatments and incur substantial economic burden.

Treatment persistence & health care costs of adult MDD patients treated with escitalopram vs. citalopram in a medicaid population.

OBJECTIVE: Compare treatment persistence and health care costs of major depressive disorder (MDD) Medicaid patients treated with escitalopram versus citalopram. DESIGN: Retrospective analysis of Medicaid administrative claims data. METHODOLOGY: Analyzed administrative claims data from the Florida Medicaid program (07/2002-06/2006) for patients ages 18-64 years with 21 inpatient claim or 2 independent medical claims for MDD. Outcomes included discontinuation and switching rates and prescription drug, medical, and total health care costs, all-cause and related to mental disorder. Contingency table analysis and survival analysis were used to compare outcomes between treatment groups, using both unadjusted analysis and multivariate analysis adjusting for baseline characteristics. RESULTS: The study included 2,650 patients initiated on escitalopram and 630 patients initiated on citalopram. Patients treated with escitalopram were less likely to discontinue the index drug (63.7% vs. 68.9%, P=0.015) or to switch to another second-generation antidepressant (14.9% vs. 18.4%, P=0.029) over the six months post-index date. Patients treated with escitalopram had $1,014 lower total health care costs (P=0.032) and $519 lower health care costs related to mental disorder (P=0.023). More than half of the total cost difference was attributable to savings in inpatient hospitalizations related to mental disorder ($571, P=0.003) and to outpatient costs ($53, P<0.001). Escitalopram therapy was also associated with $736 lower medical costs related to mental disorder (P=0.009). CONCLUSION: In the Florida Medicaid program, compared to adult MDD patients initiated on citalopram, escitalopram patients have better treatment persistence and lower total health care costs due to any cause and due to mental disorder, mostly driven by lower hospitalization costs related to mental disorder.

Hypoglycemia, treatment discontinuation, and costs in patients with type 2 diabetes mellitus on oral antidiabetic drugs.

OBJECTIVE: To investigate the rate and impact of hypoglycemic events among patients with type 2 diabetes mellitus (T2DM) receiving different classes of oral antidiabetic drugs (OADs). RESEARCH DESIGN AND METHODS: Adult patients with T2DM were extracted from the Ingenix IMPACT claims database. The mean number of health care visits due to hypoglycemic events per patient-year was estimated. Multivariate regression models were used to: 1) assess the risk factors for experiencing a hypoglycemic event; 2) assess the effect of experiencing hypoglycemic events on antidiabetic treatment discontinuation; and 3) compare 12-month post-index date costs between patients with and without hypoglycemic events. RESULTS: 212 061 patients with T2DM were included in the analysis. The estimated frequency of hypoglycemia-related health care visits was 0.054 per patient-year. Insulin use was associated with increased risk of developing hypoglycemia, followed by use of sulfonylureas and other OADs (eg, meglitinide and α-glucosidase inhibitors). The impacts of thiazolidinediones, metformin, and dipeptidyl peptidase-4 on hypoglycemia risk were relatively small. Having a hypoglycemic event was associated with significantly increased risk of antidiabetic treatment discontinuation. Patients with hypoglycemia showed significantly higher annual all-cause and diabetes-related health care costs than patients without hypoglycemia (adjusted Δ = +$5024 and +$3747, respectively; both P < 0.0001). CONCLUSION: Different OAD classes were associated with different levels of risk for hypoglycemic events. Hypoglycemia was associated with a higher risk of antidiabetic treatment discontinuation and significantly increased health care costs.

Risks of developing psychiatric disorders in pediatric patients with psoriasis.

BACKGROUND: Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people. OBJECTIVE: We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects. METHODS: Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1:5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders. RESULTS: Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P = .0001; hazard ratio = 1.25; P = .0001), especially depression (3.01% vs 2.42%; P = .0036; hazard ratio = 1.25; P = .0053) and anxiety (1.81% vs 1.35%; P = .0048; hazard ratio = 1.32; P = .0045). LIMITATIONS: Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures. CONCLUSIONS: Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects.

The effects of adalimumab treatment and psoriasis severity on self-reported work productivity and activity impairment for patients with moderate to severe psoriasis.

BACKGROUND: Psoriasis significantly impairs work productivity and daily activities. OBJECTIVES: We sought to examine the effects of adalimumab on psoriasis-related work productivity and activity impairment and associations between the impairment and psoriasis severity in patients with moderate to severe psoriasis. METHODS: Data were from the first 16 weeks of the Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis TriAL (REVEAL). Outcomes as measured by the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI-Psoriasis) included employment status, total work productivity impairment, and total activity impairment. Logistic regression and analyses of covariance were used to assess the effects of adalimumab and treatment response (≥ 75% improvement in Psoriasis Area and Severity Index responders) on WPAI-Psoriasis outcomes. Longitudinal generalized estimating equations and Pearson correlation coefficients were used to assess associations between WPAI outcomes and psoriasis severity. RESULTS: Greater improvements in total work productivity impairment and total activity impairment were observed with adalimumab treatment versus placebo (15.5 and 11.1 percentage points, respectively; P < .001). Unemployment rate, total work productivity impairment, and total activity impairment were significantly associated with greater baseline psoriasis severity. Changes in WPAI outcomes were significantly correlated with greater psoriasis severity. The Dermatology Life Quality Index had stronger associations with changes in WPAI outcomes compared with clinical severity measures (Psoriasis Area and Severity Index and Physician Global Assessment). LIMITATIONS: REVEAL only included WPAI data for 16 weeks. Therefore, long-term impact of adalimumab treatment on productivity outcomes could not be assessed. In addition, information on occupational job title or industry was not collected and data were not adjusted for psoriatic arthritis. CONCLUSIONS: Adalimumab reduced psoriasis-related work productivity and activity impairment in patients with moderate to severe psoriasis.

Effect of adalimumab on clinical laboratory parameters in patients with Crohn's disease: results from the CHARM trial.

BACKGROUND: Nutritional deficiencies and anemia are common in Crohn's disease (CD). METHODS: We evaluated the effect of adalimumab on changes in laboratory values using data from CHARM, in which patients were randomized to adalimumab 40 mg every other week (eow), adalimumab 40 mg weekly, or placebo for 56 weeks. Mean changes in laboratory values from baseline to Weeks 26 and 56 were compared between adalimumab and placebo using analysis of covariance models. Percentages of patients with suboptimal laboratory values at Weeks 26 and 56 were compared between treatment groups using Cochran-Mantel-Haenszel (CMH) tests. Pearson correlation coefficients for associations between changes in Crohn's Disease Activity Index (CDAI) score and changes in laboratory values were estimated at Weeks 4, 26, and 56. RESULTS: The intention-to-treat analysis included 778 patients randomized to adalimumab eow (N = 260), adalimumab weekly (N = 257), or placebo (N = 261). Baseline abnormalities in laboratory values were common across treatment groups. CMH tests revealed significantly lesser rates of suboptimal laboratory values with adalimumab vs. placebo at Week 26, including hypoalbuminemia, calcium deficiency, low hemoglobin, low hematocrit, low red blood cell count, elevated platelet count, and elevated C-reactive protein concentration (all P < 0.05). These improvements persisted at Week 56. Improvements in CDAI from baseline to Weeks 4, 26, and 56 were significantly correlated with changes from baseline for albumin, hemoglobin, and C-reactive protein (all P < 0.001). CONCLUSIONS: Adalimumab therapy for moderately to severely active CD was associated with significant improvements in nutritional, hematologic, and inflammatory markers.

Comorbidity burden, healthcare resource utilization, and costs in chronic gout patients refractory to conventional urate-lowering therapy.

Patients with chronic gout refractory to conventional urate-lowering therapy have high rates of flares and incidence of tophi, which impose a significant disease and potentially economic burden. This study examined healthcare resource use and costs stratified by disease burden. Adult patients diagnosed with gout (ICD-9-CM:274.xx) and having had ≥3 flares defined by clinical surrogates within a 12-month period were selected for the case cohort from the Thomson MarketScan databases (2003/Q3-2008/Q3). Only patients who had received allopurinol treatment and a diagnosis of tophi (ICD-9-CM:274.8x) at any time before the first flare (index date) or within 12 months postindex were included and were matched in a 1:1 ratio with control gout-free subjects. The comorbidity burden, healthcare resource use, and annual healthcare costs (2008 US$) in the 12-month postindex period were compared between both cohorts using regression models adjusted for demographic characteristic and stratified for patients with ≥6 flares. A total of 679 gout patients met the inclusion criteria for the study and had a higher prevalence of comorbidities than their matched controls. Gout cohort had a significantly higher incidence of emergency room, hospitalizations, outpatient visits, and other medical services than did their matched controls (all comparisons, uncorrected P < 0.01). After adjusting for baseline characteristics, the refractory gout cohort incurred an incremental total annual healthcare cost of $10,222 where 40% of the annual medical cost was for gout-related care compared with control cohort (P < 0.01). Patients with refractory gout have a significant economic burden compared with a gout-free population.

Cost-effectiveness analysis of roflumilast/tiotropium therapy versus tiotropium monotherapy for treating severe-to-very severe COPD.

OBJECTIVE: To conduct a cost-effectiveness analysis comparing roflumilast/tiotropium therapy vs tiotropium monotherapy in patients with severe-to-very severe COPD. METHODS: The economic evaluation applied a disease-based Markov cohort model with five health states: (1) severe COPD, (2) severe COPD with a history of severe exacerbation, (3) very severe COPD, (4) very severe COPD with a history of severe exacerbation, and (5) death. Within a given health state, a patient may have a mild/moderate or severe exacerbation or die. Data from roflumilast clinical trials and published literature were used to populate model parameters. The model calculated health outcomes and costs for roflumilast/tiotropium therapy vs tiotropium monotherapy over a 5-year horizon. Incremental cost and benefits were then calculated as cost-effectiveness ratios, including cost per exacerbation avoided and cost per quality adjusted life year ($/QALY). RESULTS: Over a 5-year horizon, the estimated incremental costs per exacerbation and per severe exacerbation avoided were $589 and $5869, respectively, and the incremental cost per QALY was $15,815. One-way sensitivity analyses varying key parameters produced an incremental cost per QALY ranging from $1963-$32,773. LIMITATIONS: A number of key parameters used in the model were obtained from studies in the literature that were conducted under different contexts. Specifically, the relative risk estimate for severe COPD patients originates from a small trial not designed to demonstrate the impact of roflumilast on frequency of exacerbations. In addition, the model extrapolates the relative risk estimates over periods of 5-30 years, even though the estimates were only observed in trials that spanned less than a year. CONCLUSIONS: The addition of roflumilast to tiotropium is cost-effective for the treatment of severe to very severe COPD patients.

Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases.

BACKGROUND: Bone metastases are common in patients with hormone-refractory prostate cancer. In a study of autopsies of patients with prostate cancer, 65%-75% had bone metastases. Bone metastases place a substantial economic burden on payers with estimated total annual costs of $1.9 billion in the United States. Skeletal-related events (SREs), including pathologic fractures, spinal cord compression, surgery to bone, and radiation to bone, affect approximately 50% of patients with bone metastases. They are associated with a decreased quality of life and increased health care costs. Zoledronic acid is an effective treatment in preventing SREs in solid tumors and multiple myeloma. Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. A Phase 3 clinical trial (NCT00321620) demonstrated that denosumab had superior efficacy in delaying first and subsequent SREs compared with zoledronic acid. However, the economic value of denosumab has not been assessed in patients with hormone-refractory prostate cancer. OBJECTIVE: To compare the cost-effectiveness of denosumab with zoledronic acid in the treatment of bone metastases in men with hormone-refractory prostate cancer. METHODS: An Excel-based Markov model was developed to assess costs and effectiveness associated with the 2 treatments over a 1- and 3-year time horizon. Because the evaluation was conducted from the perspective of a U.S. third-party payer, only direct costs were included. Consistent with the primary outcome in the Phase 3 trial, effectiveness was assessed based on the number of SREs. The model consisted of 9 health states defined by SRE occurrence, SRE history, disease progression, and death. A hypothetical cohort of patients with hormone-refractory prostate cancer received either denosumab 120 mg or zoledronic acid 4 mg at the model entry and transitioned among the 9 health states at the beginning of each 13-week cycle. Transition probabilities associated with experiencing the first SRE, subsequent SREs, disease progression, and death were primarily derived from the results of the Phase 3 clinical trial and were supplemented with published literature. The model assumed that a maximum of 1 SRE could occur in each cycle. Drug costs included wholesale acquisition cost, health care professional costs associated with drug administration, and drug monitoring costs, if applicable. Nondrug costs included incremental costs associated with disease progression, costs associated with SREs, and terminal care costs, which were derived from the literature. Adverse event (AE) costs were estimated based on the incidence rates reported in the Phase 3 trial. Resource utilization associated with AEs was estimated based on consultation with a senior medical director employed by the study sponsor. All costs were presented in 2010 dollars. The base case estimated the incremental total cost per SRE avoided over a 1-year time horizon. Results for a 3-year time horizon were also estimated. One-way sensitivity analyses and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the model. RESULTS: In the base case, the total per patient costs incurred over 1 year were estimated at $35,341 ($19,230 drug costs and $16,111 nondrug costs) for denosumab and $27,528 ($10,960 drug costs and $16,569 nondrug costs) for zoledronic acid, with an incremental total direct cost of $7,813 for denosumab. The estimated numbers of SREs per patient during the 1-year period were 0.49 for denosumab and 0.60 for zoledronic acid, resulting in an incremental number of SREs of -0.11 in the denosumab arm. The estimated incremental total direct costs per SRE avoided with the use of denosumab instead of zoledronic acid were $71,027 for 1 year and $51,319 for 3 years. The 1-way sensitivity analysis indicated that the results were sensitive to the drug costs, median time to first SRE, and increased risk of SRE associated with disease progression. Results of the PSA showed that based on willingness-to-pay thresholds of $70,000, $50,000, and $30,000 per SRE avoided, respectively, denosumab was cost-effective compared with zoledronic acid in 49.5%, 17.5%, and 0.3% of the cases at 1 year, respectively, and 79.0%, 49.8%, and 4.1% of the cases at 3 years, respectively. CONCLUSIONS: Although denosumab has demonstrated benefits over zoledronic acid in preventing or delaying SREs in a Phase 3 trial, it may be a costly alternative to zoledronic acid from a U.S. payer perspective.

Clinical and economic outcomes of multiple versus single long-acting inhalers in COPD.

OBJECTIVE: To compare healthcare resource utilization and healthcare costs between COPD patients who used multiple long-acting inhalers versus those who used a single long-acting inhaler. METHODS: COPD patients meeting study inclusion criteria were identified in the Market Scan database (2004-2008) and were classified as being a multiple- or single-inhaler user. 11,747 multiple- and single-inhaler users were matched on baseline characteristics to balance disease severity. Patients were followed for 12 months. Incremental differences between the two groups were estimated for: number of exacerbations; time to first exacerbation; all-cause and COPD-related inpatient admissions, inpatient days, emergency room visits, urgent care visits, outpatient visits, and other medical services visits; all-cause and COPD-related healthcare costs. Multivariate regression analyses were also used to control for a number of potentially confounding factors. RESULTS: After controlling for a number of potentially confounding factors, multiple-inhaler users experienced significantly more exacerbations (0.52; p < .0001) and had a higher risk of exacerbation (HR = 1.40; p < .0001) than single-inhaler users. Multiple-inhaler users also incurred significantly more inpatient admissions (IRR = 1.15; p < .0001), inpatient days (IRR = 1.20; p < .0001), urgent care visits (IRR = 1.10; p = 0.0026), outpatient visits (IRR = 1.06; p < .0001), and other medical services visits (IRR = 1.12; p = <.001) than single-inhaler users, resulting in significantly higher all-cause health care costs ($3,319; p < .0001). Results of COPD-related resource use and costs were comparable. CONCLUSIONS: After controlling for a number of potentially confounding factors, multiple-inhaler users had more exacerbations, a higher risk of exacerbation, and higher healthcare resource utilization and costs compared to single-inhaler users.

Healthcare costs associated with bevacizumab and cetuximab in second-line treatment of metastatic colorectal cancer.

OBJECTIVE: To compare the health care costs of patients with metastatic colorectal cancer (mCRC) who received second-line treatment with Avastin (bevacizumab) versus Erbitux (cetuximab), from the third-party payer's perspective. METHODS: Patients with mCRC were selected from the PharMetrics claims database if they received second-line therapy containing either bevacizumab (second-line bevacizumab cohort) or cetuximab (second-line cetuximab cohort). Six-month costs following second-line therapy start date and average monthly healthcare costs while on second-line therapy (in 2009 US$) were calculated and compared between the two groups. RESULTS: A total of 2188 patients with mCRC who met the eligibility criteria were included in the analysis, including 1808 patients receiving bevacizumab and 380 patients receiving cetuximab in second-line treatment. Demographic and baseline characteristics were similar between the two groups. Patients' mean age was 61 years and 56% were males. In second-line treatment, bevacizumab was commonly used with oxaliplatin (43.5%) and irinotecan-based regimens (40.4%), whereas cetuximab was commonly used with irinotecan-based regimens (68.2%). Bevacizumab patients had significantly lower total all-cause healthcare costs than cetuximab patients (adjusted difference: -$10,231, p = 0.020), and lower medical costs (-$10,796, p = 0.012) during the 6 months following second-line therapy initiation. Approximately half of the difference in total all-cause healthcare costs was attributable to the lower chemotherapy and targeted therapy costs (-$5635, p = 0.032) of bevacizumab patients than those of cetuximab patients. While on second-line therapy, bevacizumab patients also had lower average monthly all-cause healthcare costs than cetuximab patients. LIMITATIONS: Second-line treatment in the current study was defined based on changes in mCRC medications, not based on disease progression due to the limited clinical information available in claims. CONCLUSION: The use of bevacizumab in second-line therapy was associated with significantly lower healthcare costs in mCRC patients, compared to the use of cetuximab.

Impact of initiation timing of SSRI or SNRI on depressed adolescent healthcare utilization and costs.

BACKGROUND: Adolescents with newly diagnosed depression may not receive timely antidepressant therapy. Clinical and economic effects of early versus late treatment initiation are unclear. OBJECTIVE: To compare effects of early versus late initiation of second-generation (SSRI/SNRI) antidepressants on emergency room (ER) visits, hospitalizations and healthcare costs in adolescents with depression. METHODS: Patients aged 12-17 with a diagnosis of depression were identified in a claims database (1999-2007). Patients initiating antidepressants within 1 month of initial diagnosis were considered early initiators; patients initiating within 2-12 months were late initiators. Clinical resource use and healthcare costs were measured during the 6-month pre-index and 12-month post-index (study) periods and compared descriptively between groups. Logistic regression compared healthcare services utilization; a generalized linear model compared costs. All models were adjusted for baseline characteristics, including demographics, comorbidities, and healthcare services utilization. RESULTS: A total of 7344 adolescents met study criteria. 4415 (60%) initiated antidepressant treatment within 1 month of diagnosis. At baseline, early initiators had more all-cause inpatient visits (14 vs. 7%) and all-cause ER visits than late initiators (25 vs. 21%, both p<0.01). They had higher medical ($1434 vs. $1160) and total costs ($1565 vs. $1290) (both p<0.01). In the study period, late initiators had higher risk of ER visits (OR=1.13, p=0.03). They incurred higher medical costs ($5415 vs. $4061) and higher total healthcare costs ($6001 vs. $4907), but lower adjusted drug costs ($767 vs. $888) (all p<0.01). LIMITATIONS: Clinical data are scarce in the claims database, and the ability to observe disease severity and reasons for delayed treatment is limited. The definition of early and late initiation was based on empirical analysis, and no clear cutoff was identified beyond what was observed in the data. CONCLUSIONS: Adolescents who initiated SSRI/SNRI therapy earlier experienced lower risk of ER visits and had lower total costs compared to late initiators.

Comparison of skeletal complications and treatment patterns associated with early vs. delayed zoledronic acid therapy in multiple myeloma.

BACKGROUND: This study retrospectively compared the risks of skeletal-related events (SREs) and zoledronic acid (ZOL) treatment discontinuation associated with early vs. delayed ZOL therapy for patients with symptomatic multiple myeloma (MM). PATIENTS AND METHODS: Data were collected from a physician-administered medical chart review among US patients with a confirmed diagnosis of symptomatic MM treated after 01/01/2002. Early and delayed ZOL therapy were defined, respectively, as initiating ZOL ≤ 60 days (N = 126) vs. > 60 days (N = 186) after the first symptomatic MM diagnosis. Kaplan-Meier analysis with a log-rank test was performed to compare the risk of SREs between the cohorts. Cox proportional hazard modeling compared the risk of SREs associated with early vs. delayed ZOL treatment, controlling for demographic factors, stage of MM, bone health status, and presence of major comorbidities at diagnosis. Time to ZOL discontinuation was evaluated using the Kaplan-Meier method, following patients from the date of ZOL initiation. RESULTS: Time to the first SRE was significantly longer for patients who received early treatment with ZOL (P = .005). At 2 years after diagnosis, the SRE-free rate was 74.6% vs. 56.5% in the early vs. delayed treatment group, respectively. Early ZOL therapy was associated with a significantly lower risk of any SRE (hazard rate [HR] = .625 vs. delayed ZOL therapy; P = .029). At 2 years from ZOL therapy initiation, rates of ZOL discontinuation were 9.6% vs. 16.4% among patients with early vs. delayed therapy, respectively (P < .05). CONCLUSION: Early treatment with ZOL was associated with significantly reduced risks of SREs and with better treatment persistence compared with delayed treatment.

Therapy persistence and adherence in patients with chronic obstructive pulmonary disease: multiple versus single long-acting maintenance inhalers.

OBJECTIVE: To compare persistence and adherence among patients with chronic obstructive pulmonary disease (COPD) treated with either multiple- or single- long-acting maintenance inhalers. METHODS: Patients with ≥2 COPD medical claims and ≥2 prescriptions for a long-acting inhaler within 1 year were classified as single- or multiple-inhaler users based on their treatment regimen (MarketScan database; 2004-2008) and matched on demographics and statistically significant baseline characteristics. Persistence, analyzed via time to treatment discontinuation, and treatment adherence, measured by proportion of days covered (PDC), were compared between the two groups over a 12-month period. Sensitivity analyses were conducted in patients with poorly and well-controlled disease. RESULTS: A total of 23,494 patients were grouped into 11,747 matched pairs. After adjusting for confounding factors, multiple-inhaler users had a significantly higher discontinuation rate [Hazard ratio = 1.40, p < 0.0001] compared with single-inhaler users. Multiple-inhaler users were less likely to be adherent than single-inhaler users with an average PDC of 0.51 (SD = 0.272) vs. 0.55 (SD = 0.279), respectively (p < 0.0001). These results were consistent for the poorly- and well-controlled disease groups. CONCLUSIONS: Multiple long-acting inhaler users demonstrated lower treatment persistence and adherence rates than single long-acting inhaler users. Limitations of the study are related to the retrospective, observational design and use of claims data.

Increased risks of developing anxiety and depression in young patients with Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is associated with substantial psychosocial burden and increased risks for mental health disorders. This retrospective cohort study compared the risks of developing anxiety disorders and depression and incidences of psychotropic medication use between young CD patients and matched CD-free controls. METHODS: Medical claims, prescription drug claims, enrollment, and demographic data for patients <18 years diagnosed with CD were obtained from the MarketScan database (1 January 2000-30 June 2006). Each CD patient was matched with five CD-free controls based on exact age, sex, and months of health plan enrollment. Incidence rates and risks of developing anxiety disorders and depression and psychotropic medication use in the 6 months after the index date were compared, as were risks of developing persistent anxiety or depression (receiving medical services related to a diagnosis of anxiety or depression or psychotropic therapy for >1 year). RESULTS: After adjustment for patient characteristics, the risks of developing anxiety disorders (hazard ratio (HR) [95% confidence interval (CI);[equals;2.28 [1.65-3.17]) and depression (HR [95% CI;[equals;1.74 [1.35-2.25]) after CD diagnosis were significantly greater for the CD cohort (N=2,144) than for CD-free controls (N=10,720). Patients with CD also had greater risks of developing persistent anxiety and persistent depression (HR [95% CI;[equals;4.35 [2.22-8.50] and 2.75 [1.73-4.38], respectively). CONCLUSIONS: Compared with matched CD-free controls, young patients with CD had significantly greater risks of developing anxiety disorders and depression, were more likely to receive psychotropic treatments, and had significantly greater risks of developing persistent anxiety and depression.

Incremental third-party costs associated with COPD exacerbations: a retrospective claims analysis.

BACKGROUND: Exacerbations are a major contributor to the large burden of treating chronic obstructive pulmonary disease (COPD). Estimates of exacerbation costs in the United States are limited. OBJECTIVE: To estimate incremental costs associated with COPD exacerbation, particularly severe exacerbation, in the United States. METHODS: COPD patients with at least one exacerbation were identified in the Thomson Reuters MarketScan administrative claims database. A COPD exacerbation was defined as patient use of oral or parenteral corticosteroids on the same day or within 7 days following a claim with a COPD diagnosis. Severe exacerbation was further defined if the exacerbation was associated with hospitalization or death. Healthcare costs and exacerbations were evaluated at quarterly intervals starting from patients' first observed claim with COPD diagnostic code in the database. Incremental costs associated with exacerbation were estimated as cost differences between quarters with exacerbation and quarters without exacerbation. RESULTS: A total of 2644,174 patient-quarters, derived from 228,978 COPD patients, were included in the analysis. The average patient was followed an average of 2.9 years. The mean total cost was $17,016 per patient-quarter with severe exacerbation, $6628 per patient-quarter with non-severe exacerbation, an average of $8726 per patient-quarters with any exacerbation compared to $4762 per patient-quarter with no exacerbation. After adjusting for patient demographics, the mean incremental total cost was $11,261 per patient-quarter with severe exacerbation, $1509 per patient-quarter for non-severe exacerbation, and $3439 per patient-quarter with any exacerbation compared with patient-quarters with no exacerbation. LIMITATIONS: The method used for defining exacerbations does not capture mild exacerbations. Additional limitations exist due to the nature of claims data. CONCLUSIONS: Exacerbations, especially severe ones, result in a significant economic burden for third-party payers. Effective management of COPD and prevention of exacerbations may lead to improved patient outcomes and reduction in total healthcare costs for long-term management of COPD.

Economic impact of therapeutic substitution of a brand selective serotonin reuptake inhibitor with an alternative generic selective serotonin reuptake inhibitor in patients with major depressive disorder.

BACKGROUND: To reduce pharmacy costs, managed care organizations encourage therapeutic substitution from brand to a generic product. However, little is known about whether these cost-containment strategies can also potentially lower total expenditures for payers in treatment of major depressive disorder (MDD). OBJECTIVE: To compare economic outcomes of patients with MDD who were switched from a brand selective serotonin reuptake inhibitor (SSRI) to an alternative generic SSRI for nonmedical reasons versus patients who continued on the brand SSRI. METHODS: Adult MDD patients in the Ingenix Impact Database (2003-2007) were considered "switchers" if they received treatment with a brand SSRI and were later switched to an alternative generic SSRI for nonmedical reasons. Patients who remained on the brand SSRI (nonswitchers) were matched 1:1 with switchers. All-cause, mental health-related, and MDD-related rates of hospitalizations/emergency department (ED) visits and costs over 6 months were compared both descriptively and by using adjusted regression models. A subgroup analysis on patients who were switched from escitalopram (Lexapro) to an alternative generic SSRI was also performed. RESULTS: The study included 4449 matched pairs. Compared with nonswitchers, switchers had higher risk of all-cause, mental health-related, and MDD-related use of hospitalizations/ED visits (OR 1.15, 1.34, and 1.54, respectively; all p < 0.01) and higher risk-adjusted mental health-related and MDD-related medical costs ($219 and $222, respectively; both p < 0.05). Subgroup analysis on escitalopram showed similar results; switchers experienced higher risk of any-cause, mental health-related, and MDD-related use of hospitalizations/ED visits (OR 1.21, 1.41, and 1.53, respectively; all p < 0.01) and higher risk-adjusted MDD-related medical costs ($151; p < 0.05). CONCLUSIONS: Compared with patients who continued on their patented SSRIs, patients who switched to a generic SSRI incurred more resource use of hospitalizations/ED visits and higher MDD-related health-care costs. The effects of therapeutic substitution should be carefully examined, because use of generic alternatives may not be a cost-saving strategy when total health-care costs are considered.