The Economic Benefit of Remission for Patients with Rheumatoid Arthritis.

INTRODUCTION: In patients with rheumatoid arthritis (RA), attaining remission or low disease activity (LDA), as recommended by the treat-to-target approach, has shown to yield improvement in symptoms and quality of life. However, limited evidence from real-world settings is available to support the premise that better disease control is associated with lower healthcare costs. This study fills in evidence gaps regarding the cost of care by RA disease activity (DA) states and by therapy. METHODS: This retrospective cohort study linked medical and prescription claims from Optum Clinformatics Data Mart to electronic health record data from Illumination Health over 1/1/2010-3/31/2020. Mean annual costs for payers and patients were examined, stratifying on DA state and baseline use of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biologics, and targeted synthetic (ts)DMARDs. Subgroup analysis examining within-person change in costs pre- and post-initiation of new therapy was also performed. Descriptive statistics, means, and boot-strapped confidence intervals were analyzed by DA state and by RA therapy. Furthermore, multivariate negative binomial regression analysis adjusting for key baseline characteristics was conducted. RESULTS: Of 2339 eligible patients, 19% were in remission, 40% in LDA, 29% in moderate DA (MDA), and 12% in high DA (HDA) at baseline. Mean annual costs during follow-up were substantially less for patients in remission ($40,072) versus those in MDA ($56,536) and HDA ($59,217). For patients in remission, csDMARD use was associated with the lowest mean annual cost ($25,575), tsDMARD was highest ($75,512), and tumor necrosis factor inhibitor (TNFi) ($69,846) and non-TNFi ($57,507) were intermediate. Among new TNFi (n = 137) and non-TNFi initiators (n = 107), 31% and 26% attained LDA/remission, respectively, and the time to achieve remission/LDA was numerically shorter in TNFi vs. non-TNFi initiators. For those on biologics, mean annual within-person medical and inpatient costs were lower after achieving LDA/remission, although pharmacy costs were higher. CONCLUSIONS: Cost of care increased with increasing DA state, with patients in remission having the lowest costs. Optimizing DA has the potential for substantial savings in healthcare costs, although may be partially offset by the high cost of targeted RA therapies.

The rate, cost and outcomes of parathyroidectomy in the united states dialysis population from 2016-2018.

BACKGROUND: In end-stage kidney disease, patients may undergo parathyroidectomy if secondary hyperparathyroidism cannot be managed medically. This study was designed to estimate the parathyroidectomy rate in the United States (US) and to quantify changes in costs and other outcomes after parathyroidectomy. METHODS: This was a retrospective observational cohort study using US Renal Data System data for 2015-2018. Parathyroidectomy rates were estimated for adult hemodialysis and peritoneal dialysis patients alive at the beginning of 2016, 2017, and 2018 who were followed for a year or until parathyroidectomy, death, or transplant. Incremental differences in economic and clinical outcomes were compared before and after parathyroidectomy in adult hemodialysis and peritoneal dialysis patients who received a parathyroidectomy in 2016 and 2017. RESULTS: The rate of parathyroidectomy per 1,000 person-years decreased from 6.5 (95% CI 6.2-6.8) in 2016 to 5.3 (95% CI 5.0-5.6) in 2018. The incremental increase in 12-month cost after versus before parathyroidectomy was $25,314 (95% CI $23,777-$27,078). By the second month after parathyroidectomy, 58% of patients had a corrected calcium level < 8.5 mg/dL. In the year after parathyroidectomy (versus before), hospitalizations increased by 1.4 per person-year (95% CI 1.3-1.5), hospital days increased by 12.1 per person-year (95% CI 11.2-13.0), dialysis visits decreased by 5.2 per person-year (95% CI 4.4-5.9), and office visits declined by 1.3 per person-year (95% CI 1.0-1.5). The incremental rate per 1,000 person years for hematoma/bleed was 224.4 (95% CI 152.5-303.1), for vocal cord paralysis was 124.6 (95% CI 59.1-232.1), and for seroma was 27.4 (95% CI 0.4-59.0). CONCLUSIONS: Parathyroidectomy was a relatively uncommon event in the hemodialysis and peritoneal dialysis populations. The incremental cost of parathyroidectomy was mostly attributable to the cost of the parathyroidectomy hospitalization. Hypocalcemia occurred in over half of patients, and calcium and phosphate levels were reduced. Clinicians, payers, and patients should understand the potential clinical and economic outcomes when considering parathyroidectomy.

The value of new drugs for advanced prostate cancer.

BACKGROUND: The US Food and Drug Administration has recently approved a number of new cancer drugs. The clinical trials that serve as the basis for new cancer drug approvals may not reflect how the drugs will perform in routine practice and do not measure the impact of the drugs on spending. The authors sought to evaluate the real-world effectiveness and value of drugs recently approved for advanced prostate cancer. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, the authors identified fee-for-service Medicare beneficiaries aged 65 years or older who began treatment with a drug approved for metastatic castration-resistant prostate cancer in 2007-2009, when only 1 drug was approved for metastatic castration-resistant prostate cancer, and in 2014-2016, when 5 additional drugs were approved. They calculated life expectancy and lifetime medical costs (ie, Medicare reimbursements) for each group. RESULTS: Between 2007-2009 and 2014-2016, life expectancy increased by 12.6 months. Lifetime medical costs increased by $87,000. The incremental cost per life-year gained was $83,000. CONCLUSION: The release of 5 new drugs coincided with increases in survival rates and spending. This study's estimates indicate that the new drugs collectively were cost-effective.

Clinical and economic burden of intravenous paclitaxel or nab-paclitaxel for metastatic breast cancer.

BACKGROUND: Intravenous (IV) taxane therapy for metastatic breast cancer (mBC) has been associated with toxicities and demanding dosing schedules, which can limit treatment effectiveness. OBJECTIVES: To assess treatment patterns, toxicities, and costs in women with mBC initiating IV paclitaxel or IV nab-paclitaxel. METHODS: Adult women diagnosed with BC from January 1, 2014, to September 30, 2018, were identified in the MarketScan Commercial and MarketScan Medicare Supplemental databases. Women had a metastatic disease diagnosis and newly initiated treatment with IV paclitaxel/nab-paclitaxel (first administration date was considered the index date), and continuous enrollment for at least 12 months prior to and at least 3 months following the index date. Treatment discontinuation, dose reductions, toxicities, and health care utilization and costs per patient per month (PPPM) were assessed over the full follow-up and the index line of IV paclitaxel/nab-paclitaxel therapy (Index LOT). RESULTS: The sample included 8890 women aged 54.6 (±10.9) years, followed for 18.9 (±13.5) months. Most (82.0%) initiated IV paclitaxel/nab-paclitaxel monotherapy; 83.1% had early discontinuation (<18 weeks of treatment) of the Index LOT. Among the 6943 women eligible for the dose-change analysis, 42.4% evidenced an IV paclitaxel/nab-paclitaxel dose reduction ≥10% during the Index LOT. The most common toxicities during the Index LOT were gastrointestinal upset (30.5%), myelotoxicity (27.0%), infection (26.2%), general symptoms (25.9%), and chemotherapy-induced peripheral neuropathy (22.7%). Over follow-up, 39.7% of women had an inpatient admission and 43.0% had an emergency department visit. The mean of all-cause total costs was $11,991 PPPM, while BC-related total costs were $5320 PPPM. CONCLUSIONS: Many mBC patients initiating IV paclitaxel/nab-paclitaxel experienced dose reductions, toxicities, and/or early discontinuation of the Index LOT, which may limit treatment effectiveness. More tolerable treatments with reduced dosing complexity could improve mBC treatment and help contain costs.

Chemotherapy-induced peripheral neuropathy in metastatic breast cancer patients initiating intravenous paclitaxel/nab-paclitaxel.

BACKGROUND: Intravenous (IV) taxanes for metastatic breast cancer (mBC) are associated with toxicities, such as chemotherapy-induced peripheral neuropathy (CIPN), which can detrimentally impact outcomes. OBJECTIVE: To assess the impact of CIPN on clinical and economic outcomes in women with mBC, initiating IV paclitaxel/ nab-paclitaxel. METHODS: Adult women in the MarketScan Commercial and Medicare Supplemental Database with a mBC diagnosis, initiating IV paclitaxel or IV nab-paclitaxel (index date = first administration) from November 1, 2013, to September 30, 2018, who had no prior neuropathy diagnoses, and continuous enrollment 12 months prior to and ≥ 3 months following index were selected. Propensity score-matched CIPN and non-CIPN cohorts were defined, based on postindex CIPN diagnosis. Clinical characteristics and all-cause and breast cancer (BC)-related health care utilization and costs per patient per month (PPPM) were compared between matched CIPN and non-CIPN cohorts during follow-up. RESULTS: Among the 5870 women with mBC initiating IV paclitaxel/nab-paclitaxel, 42.7% developed CIPN. The matched cohorts each included 1950 women. Patients with CIPN were more likely to have a dose reduction (46.1% vs 38.2%, P < .001) or develop depression, diabetes, insomnia, liver dysfunction, or arthritis compared with the non-CIPN cohort, P < .05. Patients with CIPN were more likely to have an inpatient admission (39.2% vs 34.9%, P < .01) or emergency department visit (46.7% vs 35.6%, P < .001), as well as all-cause and BC-related costs that were $1102 and $725 PPPM higher, respectively, than women without CIPN (P < .01). CONCLUSIONS: CIPN was common in women, following IV paclitaxel/nab-paclitaxel treatment and was associated with dose reductions, the development of comorbidities, and elevated health care costs. Therapies for mBC that offer increased tolerability are needed to help improve patient outcomes and control costs.

Cost of home vs clinic administration of paclitaxel in metastatic breast cancer.

OBJECTIVES: To estimate the costs associated with home administration of oral paclitaxel and encequidar (novel P-glycoprotein pump inhibitor allowing oral paclitaxel bioavailability) compared with clinic/office administration of intravenous (IV) paclitaxel (175 mg/m2) and protein-bound paclitaxel in US patients with metastatic breast cancer. STUDY DESIGN: Economic analysis. METHODS: A cost calculator was constructed from a payer's perspective including all costs related to administration of the chemotherapies, including drug administration, premedications and concomitant medications, oncologist office visits, laboratory testing, and administration-related adverse events. Total administration cost per patient per month (PPPM) and 6-month costs per patient were estimated for oral paclitaxel and encequidar, 175 mg/m2 IV paclitaxel, and protein-bound paclitaxel. Three scenarios for oral paclitaxel and encequidar, a weekly IV paclitaxel scenario (80-100 mg/m2), and univariate sensitivity analyses were conducted. RESULTS: Home administration of oral paclitaxel and encequidar was associated with a total administration cost of $523 PPPM, 64.4% lower than once-every-3-weeks IV paclitaxel (175 mg/m2; $1469 PPPM) and 63.8% lower than protein-bound paclitaxel (260 mg/m2; $1445 PPPM). Difference in costs was driven largely by higher administration and premedication costs associated with IV therapies. Scenario analyses showed that increased clinical experience with home administration of oral paclitaxel and encequidar was associated with reduction in cost of care associated with its administration over time. For the weekly IV (80-100 mg/m2) paclitaxel scenario, the total administration cost was $2510 PPPM (4.8 times higher than for oral paclitaxel and encequidar). Univariate sensitivity analysis demonstrated that the model findings were robust. CONCLUSIONS: Home administration of oral paclitaxel and encequidar was associated with lower administration costs compared with once-every-3-weeks IV paclitaxel (175 mg/m2) and protein-bound paclitaxel, resulting in potential cost savings for payers.

Real-world outcomes in patients with chronic obstructive pulmonary disease initiating long-acting mono bronchodilator therapy.

BACKGROUND: Randomized clinical trials have shown long-acting mono bronchodilator therapy to be efficacious in improving lung function and dyspnea, while reducing exacerbations; however, less is known regarding the effectiveness in routine clinical practice. This study examined treatment patterns, rescue medication use, healthcare resource utilization and costs, and exacerbations in patients with chronic obstructive pulmonary disease (COPD) who initiated long-acting mono bronchodilator therapy in real-world settings. METHODS: This retrospective study used US claims data from adult patients with COPD initiating long-acting mono bronchodilator therapy between 1 January 2008 and 31 January 2015. Patients were required to have continuous health plan enrollment 12 months prior to (baseline period) and 12 months following therapy initiation (follow-up period). Outcomes, including treatment patterns, rescue medication use, exacerbations, and healthcare utilization and costs, were measured until the earliest of treatment augmentation or discontinuation, death, health plan disenrollment, or the end of the study period. Results were analyzed descriptively for all measures. Baseline and follow-up measures of all-cause and COPD-related healthcare costs and exacerbations [per patient per month (PPPM)] were compared using paired t tests. RESULTS: Among 27,394 patients with a mean follow up of 6.3 months, 18.2% augmented, 74.2% discontinued, and 7.6% continued long-acting mono bronchodilator therapy. Rescue medication use was prevalent during the follow-up period, with an average of 1.0 short-acting ß agonist (SABA) fills/month and 0.8 short-acting muscarinic antagonist (SAMA) fills/month, among patients with at least one fill for the medication of interest. PPPM mean number of exacerbations was more than triple (0.17 versus 0.05, p < 0.001) and PPPM exacerbation-related costs were more than double over the follow-up period compared with baseline ($1070 versus $485). COPD-related costs accounted for 50% of all-cause costs during the follow-up period and were significantly higher compared with baseline ($1206 versus $592, p < 0.001). CONCLUSIONS: Patients initiating long-acting mono bronchodilator therapy had high rates of medication discontinuation or augmentation. Patients used more rescue medications and experienced significantly more COPD exacerbations with higher healthcare costs compared with baseline. Further research is warranted to determine whether more aggressive initial therapy would result in symptom improvement.

Impact of Nonadherence to Inhaled Corticosteroid/LABA Therapy on COPD Exacerbation Rates and Healthcare Costs in a Commercially Insured US Population.

BACKGROUND: Evidence of poor patient adherence to medications for chronic obstructive pulmonary disease (COPD) is well-documented, but its impact on disease exacerbation rates and associated healthcare costs remains unclear. OBJECTIVE: To assess the association between adherence levels to different inhaled corticosteroid/long-acting ß2-adrenergic agonist (LABA) and COPD exacerbation rates and costs in a commercially insured population. METHODS: In this observational cohort study, patients with COPD (aged ≥40 years) who were treatment-naïve to inhaled corticosteroid/LABA and were initiating budesonide plus formoterol or fluticasone plus salmeterol between March 1, 2009, and January 31, 2014, were identified in a national representative claims database and were followed for up to 12 months. The date of the first prescription fill for either drug was defined as the index date. Patients were divided into 4 cohorts based on adherence to the index therapy, which was measured by proportion of days covered (PDC); the cohorts were classified as adherent (PDC ≥0.8), mildly nonadherent (0.5 ≤ PDC <0.8), moderately nonadherent (0.3 ≤ PDC <0.5), and highly nonadherent (PDC <0.3). Each nonadherent group was matched in a 1:1 ratio to the adherent group independently, based on prognostically important variables, using propensity score analyses. Exacerbation rates and healthcare costs were analyzed for 1 year after treatment initiation. RESULTS: During the study period, 13,657 eligible patients with COPD initiated inhaled corticosteroid/LABA; of these, only 1898 (13.9%) patients were adherent during follow-up. Group matching resulted in 1572 patients per group for comparison 1 (adherent vs mildly nonadherent), 1604 patients for comparison 2 (adherent vs moderately nonadherent), and 1755 patients for comparison 3 (adherent vs highly nonadherent). The moderately and highly nonadherent cohorts had higher exacerbation rates than the adherent patients (comparison 2: rate ratio [RR], 1.11; 95% confidence interval [CI], 1.01-1.21; P = .03; comparison 3: RR, 1.11; 95% CI, 1.01-1.21; P = .02). Adherent patients incurred significantly lower healthcare costs than all the nonadherent groups (comparison 1, $22,671 vs $25,545; P <.01; comparison 2, $22,508 vs $24,303; P <.01; comparison 3, $22,460 vs $25,148; P <.01). CONCLUSIONS: Patients adhered to their inhaled corticosteroid/LABA treatments had lower COPD exacerbation rates and lower healthcare costs compared with the moderately and highly nonadherent patients. Better adherence to maintenance therapies may help to reduce the clinical and economic burdens of COPD.

Lipid-lowering treatment modifications among patients with hyperlipidemia and a prior cardiovascular event: a US retrospective cohort study.

BACKGROUND: Numerous studies demonstrate that, even with use of statins, many patients are unable to meet their LDL-C goals. This study examined modifications to statin and/or ezetimibe therapy among patients with hyperlipidemia and prior history of cardiovascular (CV) events in a US commercially insured population. METHODS: Adults (age ≥18 years) initiating statins and/or ezetimibe between 1 January 2007 and 31 December 2008 were identified from HealthCore Integrated Research Database. The index date was the initiation date of statins and/or ezetimibe. All patients had ≥1 medical claims related to myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, or percutaneous coronary intervention within 12 months prior to the index date. Treatment modifications to statins and/or ezetimibe initiated on the index date (index therapy) included permanent discontinuation of any lipid lowering therapy (LLT), rechallenge, switching, subtraction, augmentation, and dose changes. RESULTS: Among 17,902 patients, around 90% initiated with statin monotherapy, followed by statin and ezetimibe combination (3.0%: 18-64 years; 3.8%: ≥65 years). Ten percent or less initiated on high intensity statins. Most common treatment modifications were rechallenging index therapy (25.2%: 18-64 years, 27.0%: ≥65 years), switching (27.5%: 18-64 years, 24.6%: ≥65 years), and permanent discontinuation of any LLT (18.6%: 18-64 years, 21.0%: ≥65 years). Only 10% of patients in both groups underwent dose escalation. CONCLUSIONS: Real-world evidence indicates that few high-risk patients initiate therapy with high-intensity statins. More than 50% of patients underwent a rechallenge or switching. Despite high CVD risk profile, approximately 20% of patients permanently discontinued any LLT. Key limitations: Pharmacy claims do not provide information on whether patients who had a pharmacy fill actually took the medication as prescribed. It is unknown whether rechallenge was a simple delay in filling a prescription or an actual rechallenge of their index therapy. Reasons for treatment discontinuations or modifications were unavailable in claims data.

A US Claims-Based Analysis of Real-World Lipid-Lowering Treatment Patterns in Patients With High Cardiovascular Disease Risk or a Previous Coronary Event.

The objective was to examine real-world treatment patterns of lipid-lowering therapies and their possible associated intolerance and/or ineffectiveness in patients with high cardiovascular disease (CVD) risk initiating statins and/or ezetimibe. Patients aged ≥18 years who initiated statins and/or ezetimibe from January 01, 2007, to June 30, 2011, were retrospectively identified from the IMS LifeLink PharMetrics Plus commercial claims database. Patients were further classified into 2 cohorts: (1) history of cardiovascular event (CVE) and (2) history of coronary heart disease risk equivalent (CHD RE). Patients had continuous health plan enrollment ≥1 year pre- and post-index date (statin and/or ezetimibe initiation date). Primary outcomes were index statin intensity, treatment modifications, possible associated statin/nonstatin intolerance and/or ineffectiveness issues (based on treatment modification), and time-to-treatment modifications. Analyses for each cohort were stratified by age group (<65 and ≥65 years). A total of 41,934 (history of CVE) and 170,344 patients (history of CHD RE) were included. On the index date, 8.8% to 25.1% of patients were initiated on high-intensity statin. Among patients aged <65, 79.2% and 48.8% of those with history of CVE and 78.6% and 47.3% of those with a history of CHD RE had ≥1 and 2 treatment modifications, respectively. Among all patients, 24.6% to 25.6% had possible statin intolerance and/or ineffectiveness issues after accounting for second treatment modification (if any). In conclusion, in patients with high CVD risk, index statin treatment modifications that imply possible statin intolerance and/or ineffectiveness were frequent; low use of high-intensity statins indicates unmet need in the management of hyperlipidemia and possible remaining unaccounted CVD residual risk.

Clinical and economic burden associated with cardiovascular events among patients with hyperlipidemia: a retrospective cohort study.

BACKGROUND: Annual direct costs for cardiovascular (CV) diseases in the United States are approximately $195.6 billion, with many high-risk patients remaining at risk for major cardiovascular events (CVE). This study evaluated the direct clinical and economic burden associated with new CVE up to 3 years post-event among patients with hyperlipidemia. METHODS: Hyperlipidemic patients with a primary inpatient claim for new CVE (myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, percutaneous coronary intervention and heart failure) were identified using IMS LifeLink PharMetrics Plus data from January 1, 2006 through June 30, 2012. Patients were stratified by CV risk into history of CVE, modified coronary heart disease risk equivalent, moderate- and low-risk cohorts. Of the eligible patients, propensity score matched 243,640 patients with or without new CVE were included to compare healthcare resource utilization and direct costs ranging from the acute (1-month) phase through 3 years post-CVE date (follow-up period). RESULTS: Myocardial infarction was the most common CVE in all the risk cohorts. During the acute phase, among patients with new CVE, the average incremental inpatient length of stay and incremental costs ranged from 4.4-6.2 days and $25,666-$30,321, respectively. Acute-phase incremental costs accounted for 61-75% of first-year costs, but incremental costs also remained high during years 2 and 3 post-CVE. CONCLUSIONS: Among hyperlipidemic patients with new CVE, healthcare utilization and costs incurred were significantly higher than for those without CVE during the acute phase, and remained higher up to 3 years post-event, across all risk cohorts.

Burden of First and Recurrent Cardiovascular Events Among Patients With Hyperlipidemia.

BACKGROUND: Acute cardiovascular (CV) events have been evaluated in patients with specific comorbidities but have not focused on patients with hyperlipidemia or on the their long-term costs. OBJECTIVES: To evaluate incidence of CV events, costs, and resource utilization among patients with hyperlipidemia and baseline risk of CV disease (CVD). METHODS: Patients (age 18 to 64 years) diagnosed with hyperlipidemia or using lipid-modifying medications were identified from administrative claims. Patients were categorized into 3 cohorts based on pre-index clinical characteristics-secondary prevention (SP; history of CV event, n = 15 613); high risk (HR; CVD, n = 47 600); and primary prevention (PP; no CV event history or CVD, n = 60 637)-and followed up to 2 years after the CV event. RESULTS: During follow-up, ≥1 new CV event occurred in 43.0% of the SP cohort, 33.9% of HR, and 20.9% of PP; and ≥3 new events occurred in 19.8% of the SP cohort, 12.9% of HR, and 5.5% of PP. Incremental total costs were $19 320 for SP, $20 003 for HR, and $17 650 for PP. Compared with patients with only 1 CV event, the mean 2-year cost was 30% higher in patients with 2 CV events and 48% higher in patients with 3 CV events. Only 50% of HR patients (with or without CV events) received statins. CONCLUSIONS: Patients with recurrent CV events had higher total health care costs during 24-month follow-up for each type of CV event. Total health care costs among patients with a CV event were higher for the initial as well as subsequent events. Statins and lipid-modifying medications were significantly underutilized in all cohorts, despite the presence of CVD.

Treatment patterns following discontinuation of adalimumab, etanercept, and infliximab in a US managed care sample.

OBJECTIVES: Because clinical guidelines do not offer clear recommendations for treatment options after discontinuing a tumor necrosis factor (TNF) blocker, this study evaluated treatment patterns within 360 days after discontinuation of TNF-blocker treatment. METHODS: The IMS LifeLink Health Plan Claims database was used to identify patients diagnosed with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis who received etanercept, adalimumab, or infliximab between January 1, 2005 and March 31, 2009. Discontinuation from index (first) TNF blocker was defined as switching to a different TNF blocker or a >45-day gap in therapy. Patients were categorized into mutually exclusive groups in descending order: (a) restart of index TNF blocker; (b) switch to another TNF blocker; (c) switch to a different biologic; (d) switch to nonbiologic therapy; or (e) no new treatment. RESULTS: Among 27,704 patients who initiated TNF-blocker therapy, 14,707 (53%) patients discontinued treatment over 1-3 years of follow-up. Within 360 days of discontinuing index TNF blocker, 53.4% of patients restarted index therapy: etanercept 59.9%, adalimumab 46.5%, and infliximab 43.1% (P < 0.001 for etanercept vs. adalimumab and infliximab). The majority of therapy restarts occurred within the first 3 months after discontinuation. Other patients switched to another TNF blocker: etanercept 17.1%, adalimumab 19.1% (P = 0.010 vs. etanercept), and infliximab 15.0% (P = 0.009 vs. etanercept). Switches from index TNF blocker to non-TNF-blocker biologic therapy were low: etanercept 1.9%, adalimumab 4.1%, and infliximab 10.7% (P < 0.001 for etanercept vs. adalimumab and infliximab). Switches from index TNF blocker to nonbiologic treatments were 5.4% for etanercept, 6.5% for adalimumab, and 6.9% for infliximab. CONCLUSIONS: Restarting of index TNF-blocker therapy occurs frequently after discontinuation, suggesting that long gaps in TNF-blocker therapy may be common. A significantly higher proportion of etanercept patients restarted their index TNF blocker within 3 months of discontinuation, compared with adalimumab and infliximab patients.

National and regional dose escalation and cost of tumor necrosis factor blocker therapy in biologic-naïve rheumatoid arthritis patients in US health plans.

OBJECTIVE: This study examined the proportion and magnitude of dose escalation nationally and regionally among rheumatoid arthritis (RA) patients treated with TNF-blockers and estimated the costs of TNF-blocker therapy. METHODS: This retrospective cohort study used claims data from US commercially-insured adult RA patients who initiated adalimumab, etanercept, or infliximab therapy between 2005-2009. Biologic-naïve patients enrolled in the health plan for ≥6 months before and ≥12 months after therapy initiation were followed for 12 months. Dose escalation was assessed using three methods: (1) average weekly dose > recommended label dose, (2) average ending dispensed dose > maintenance dose, and (3) average dose after maintenance dose > maintenance dose. Annual cost of therapy included costs for mean dose and drug administration fees. RESULTS: Overall, 1420 etanercept, 874 adalimumab, and 454 infliximab patients were included. A significantly lower proportion of etanercept-treated patients had dose escalation using the average weekly dose (3.9% vs 21.4% adalimumab and 69.6% infliximab; p < 0.0001), average ending dispensed dose (1.1% vs 10.6% adalimumab and 63.0% infliximab; p < 0.0001), and average dose after maintenance dose methods (2.8% vs 15.7% adalimumab and 69.6% infliximab; p < 0.0001). Regional dose escalation rates and magnitudes of escalation were directionally consistent with national rates. Etanercept had the lowest cost per treated RA patient ($19,690) compared to adalimumab ($23,020) and infliximab ($24,030). LIMITATIONS: Exclusion of patients not on continuous TNF-blocker therapy limits the generalizability; however, ∼50% of patients were persistent on therapy for 12 months. The study population comprised RA patients in commercial health plans, thus the results may not be generalizable to Medicare or uninsured populations. CONCLUSIONS: In this retrospective study, etanercept patients had the lowest proportions and magnitudes of dose escalation across all methods compared to adalimumab and infliximab patients nationally and regionally. Mean annual cost was lowest for etanercept-treated patients.

Dosing patterns of three tumor necrosis factor blockers among patients with rheumatoid arthritis in a large United States managed care population.

OBJECTIVE: To describe dosing patterns of etanercept, adalimumab, and infliximab in rheumatoid arthritis (RA) patients in US managed care. METHODS: This retrospective analysis included adult (18-64 years) RA patients in the HealthCore Integrated Research Database with ≥ 1 claim for etanercept, adalimumab, or infliximab between 7/1/2007 and 1/31/2010. Patients had 6 months pre-index and 12 months post-index claim eligibility. Patients without any TNF blocker claim during the pre-index period were considered new patients and patients with a TNF blocker claim during the pre-index period were considered continuing patients. Persistence, discontinuation, switch, and dose escalation patterns were evaluated. Patients with 1-year persistence were evaluated for dose escalation using two methods: (1) average weekly dose and (2) increase from 50 mg to 75 mg or 100 mg weekly of etanercept or from 40 mg every other week to 40 mg weekly of adalimumab or increase in vial or decreased infusion interval for infliximab. RESULTS: Data from 2426 patients were analyzed (1595 etanercept; 417 adalimumab; 414 infliximab). Persistence ≥ 1 year on index medication was reported in 62.2% and 89.2% of new and continuing patients on etanercept, respectively, 66.0% and 94.0% on adalimumab, and 68.9% and 96.4% on infliximab. Discontinuation occurred in 19.7% and 7.9% of new and continuing patients on etanercept, respectively, 20.6% and 4.5% on adalimumab, and 18.8% and 2.1% on infliximab. Switching occurred in 12.2% and 4.3% of new and continuing patients on etanercept, respectively, 9.1% and 1.8% on adalimumab, and 10.4% and 2.1% on infliximab. Dose escalation was lower with etanercept (0.4-2.6%) than adalimumab (12.6-24.3%) or infliximab (40.0-79.5%) (P < 0.0001). CONCLUSIONS: Discontinuation and switching were common within 1 year of initiating etanercept, adalimumab, and infliximab in patients with RA in this analysis. Study limitations included the restricted patient age range; analysis of three TNF blockers; study period (prior to approval of additional agents); and missing reasons for treatment changes.

Treatment patterns in the first year after initiating tumor necrosis factor blockers in real-world settings.

BACKGROUND: Tumor necrosis factor (TNF)-blockers are approved for use in several immune-related conditions, but treatment patterns, such as switching between TNF blockers or restarting treatment after a gap in therapy, are not clearly established. This analysis examined TNF blocker treatment patterns within the first year after initiating treatment with etanercept, adalimumab, or infliximab in patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. METHODS: Administrative claims data from the MarketScan® Commercial Claims and Encounters Database (Thomson Reuters, Ann Arbor, MI, USA) were analyzed for patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis who were continuously enrolled and newly initiated etanercept, adalimumab, or infliximab treatment between January 1, 2005 and July 1, 2009. Persistence (no treatment gap ≥45 days), restarting index therapy (after a ≥45-day treatment gap), switching to a different biologic of interest (certolizumab, golimumab, ustekinumab, alefacept, abatacept, rituximab, or tocilizumab), and stopping (≥45-day treatment gap with no restart or switch) were analyzed for the first year after the index date. RESULTS: A total of 8,454 patients had an index claim for etanercept (n = 4,224), adalimumab (n = 2,941), or infliximab (n = 1,289). Treatment patterns in the first year across all four conditions combined for etanercept, adalimumab, or infliximab, respectively, were: persistence, 42%, 47%, and 56%; restarting, 25%, 19%, and 12%; switching, 13%, 12%, and 13%; and stopping, 20%, 22%, and 19%. The combined rates of either persistence or restarting initial therapy after a treatment gap were 67%, 66%, and 68%, for etanercept, adalimumab, and infliximab, respectively. Most switches (66-92%) were between the three TNF blockers. CONCLUSION: In the first year after initiating TNF blocker therapy, patients often have a ≥45-day treatment gap; however, approximately two-thirds of patients are either persistent with or restart their index therapy in the year following TNF blocker initiation.

Etanercept and adalimumab treatment patterns in psoriatic arthritis patients enrolled in a commercial health plan.

INTRODUCTION: Treatment patterns, including persistence, gaps in therapy, switching, and discontinuation, were examined in patients with psoriatic arthritis (PsA) who received the tumor necrosis factor (TNF)-blockers etanercept or adalimumab. METHODS: This retrospective study utilized administrative claims data from a United States commercial health plan. Adults (age 18-64 years) with PsA who started therapy with etanercept or adalimumab as index therapy between January 1, 2006 and December 31, 2008 were included in the analysis. Patients were continuously enrolled in the health plan for at least 6 months before and at least 12 months after the start of index therapy. Initial TNF-blocker dose and rates of therapy persistence (continuous use of index medication without a gap of at least 60 days), therapy gaps, and discontinuation (gap in therapy of at least 60 days) were estimated. Those who discontinued were further classified as: (1) discontinued all biologic therapy, (2) restarted index medication, (3) switched to another biologic therapy, or (4) other. RESULTS: A total of 346 patients with PsA (202 etanercept, 144 adalimumab) were eligible. Most (90.6% etanercept; 88.9% adalimumab) started index therapy at the labeled dose. Persistence with index therapy for 12 months was observed in 50% of patients on etanercept and 45% of patients on adalimumab (P = 0.37). Patients on etanercept had a longer duration of persistence (434 vs. 353 days; P = 0.02), more pauses of at least 7 days (4.7 vs. 3.5; P = 0.004), and a longer mean pause length (48.6 vs. 29.3 days; P = 0.01) than patients on adalimumab. Of patients who discontinued (24.8% etanercept; 35.1% adalimumab), 46.4% and 41.5% restarted etanercept and adalimumab, respectively; 24.8% and 35.1% discontinued all TNF-blockers; 20.0% and 19.2% switched to another biologic; and 8.8% and 4.3% had other therapy changes. CONCLUSIONS: Approximately half of PsA patients were persistent on their index TNF-blocker for 12 months. Pauses in therapy and therapy discontinuation were common, but more than 40% of patients restarted their index TNF-blocker after discontinuation.

Change in health status (EQ-5D) over 5 years among individuals with and without type 2 diabetes mellitus in the SHIELD longitudinal study.

BACKGROUND: Health-related quality of life studies among adults with type 2 diabetes mellitus, using the EQ-5D, have been short term and have not assessed change over years. This study assessed the change in health status and health-related quality of life over 5 years among individuals with and without diabetes. METHODS: Respondents to the US Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD) completed the EuroQol-5D (EQ-5D) at baseline (2004) and 5 years later (2009). Visual analog scale (VAS) score and health index score were computed at baseline and year 5, and the change over 5 years was measured for individuals with type 2 diabetes mellitus (T2DM) and those without diabetes, and T2DM adults with and without diabetic complications. Linear regression models were used to determine change in EQ-5D score, controlling for age, gender, race, education, household income, and body mass index (BMI). RESULTS: There was significantly greater decline in the EQ-5D index score in the T2DM group (-0.031 [SD 0.158]), compared with those without diabetes (-0.016 [0.141], p = 0.001). Compared with respondents without diabetes, those with T2DM had a larger reduction in EQ-5D index score, after controlling for demographics (p = 0.001). EQ-5D VAS score declined over 5 years for both groups: -1.42 (18.1) for the T2DM group, and -0.63 (15.8) for the group without diabetes, but the between-group difference was not significant either before (p = 0.09) or after (p = 0.12), controlling for demographics. T2DM respondents with diabetic complications had a greater decline in EQ-5D scores than T2DM respondents without complications (p < 0.05). CONCLUSION: Over a 5-year period, health status of respondents with T2DM declined significantly compared with those with no diabetes, indicating that the burden of the disease has a long-term detrimental impact. This decline in health status is likely to impact utility scores (fewer quality-adjusted life years) for economic evaluations.

Cost per treated patient for etanercept, adalimumab, and infliximab across adult indications: a claims analysis.

INTRODUCTION: This paper aims to estimate the annual cost of etanercept, adalimumab, and infliximab per treated patient across adult indications using US-managed care drug use data. METHODS: Adult patients who used etanercept, adalimumab, or infliximab were identified in the Thomson Reuters MarketScan® Commercial Claims and Encounters Database (Thomson Reuters Healthcare, Ann Arbor, MI, USA) between January 1, 2005 and June 30, 2009. The index event was the first use of etanercept, adalimumab, or infliximab preceded by a diagnosis for rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Patients were defined as either newly initiating or continuing tumor necrosis factor (TNF) blocker treatment based on their use during the 6 months before the index event. Annual cost per treated patient was the sum of the etanercept, adalimumab, and infliximab medication and administration costs during the 12 months following the index claim. Annual costs were calculated across all patients as well as within each indication group and patient type (new initiator or continuing). RESULTS: In total, 21,652 patients met the study criteria (etanercept n = 12,065; adalimumab n = 5,685; infliximab n = 3,902); 43% of patients were new initiators. Patient characteristics were similar across treatment groups in terms of age (mean = 49, SD = 10) and gender (66% female). Across indications, the mean annual TNF-blocker cost per treated patient was $15,345 for etanercept, $18,046 for adalimumab, and $24,018 for infliximab. In new initiators, the TNF-blocker cost per treated patient across indications was $14,543 for etanercept, $16,978 for adalimumab, and $21,086 for infliximab; among patients continuing therapy, annual costs were $15,836 for etanercept, $19,457 for adalimumab, and $25,748 for infliximab. CONCLUSION: Patients on etanercept had the lowest TNF-blocker cost per treated patient for adult indications when applying actual drug use from a US-managed care population. TNF-blocker costs per treated patient on adalimumab and infliximab were approximately 18% and 57% higher than etanercept, respectively, using real-world drug use data.

Tumor necrosis factor blocker dose escalation among biologic naïve rheumatoid arthritis patients in commercial managed-care plans in the 2 years following therapy initiation.

OBJECTIVE: This study uses real-world US managed-care claims data to estimate dose escalation rates over the first and second years of therapy among biologic naïve rheumatoid arthritis (RA) patients initiating tumor necrosis factor (TNF) blocker therapy with etanercept, adalimumab, or infliximab. METHODS: Non-elderly adult (age 18-65 years) RA patients initiating etanercept, adalimumab, or infliximab from July 1, 2005 to April 30, 2009, were identified using the MarketScan Commercial Database. National and regional dose-escalation patterns were evaluated 12 and 24 months after initiation. In the single-instance method, dose escalation was defined as having one average weekly dose 115%, 130%, or 150% greater than the initial average weekly dose. By the two-instances method, dose escalation was defined as having two consecutive claims with an average weekly dose 115% or 130% greater than the initial average weekly dose. RESULTS: A total of 2747 patients met the inclusion criteria (mean age 50 years [SD=10]; 74% female). More patients initiated etanercept (44%) than adalimumab (37%) or infliximab (20%). Using the single-instance method, dose escalation at 12 months ranges were 0.8-1.5% for etanercept, 10.8-12.5% for adalimumab, and 16.4-42.5% for infliximab; ranges at 24 months were 0.8-2.1% for etanercept, 14.3-17.5% for adalimumab, and 26.4-57.6% for infliximab. The two-instances method showed a similar relationship among the treatment cohorts at both 12 and 24 months, with lower dose-escalation rates for etanercept (0.8%, 0.8%) than adalimumab (8.7%, 13.3%) or infliximab (22.9%, 37.6%) at the 130% threshold (p<0.001). Dose-escalation rates for etanercept, adalimumab, and infliximab were consistent across US geographic regions. CONCLUSION: Patients initiating etanercept had lower rates of dose escalation than patients initiating adalimumab or infliximab in the first and second year following therapy initiation, as well as across US geographic regions. These results may not be generalizable to the entire US RA population.