Cost-effectiveness of Evolocumab in Patients With High Cardiovascular Risk in Spain.

PURPOSE: Our objective was to assess the cost-effectiveness of evolocumab in patients at high risk of cardiovascular (CV) events from the Spanish National Health System perspective. METHODS: A Markov model was used to assess the cost-effectiveness (incremental [∆] cost per ∆ quality-adjusted life-year [QALY]; or cost utility) of evolocumab plus standard of care (SoC; statins) versus SoC, assuming lifetime treatment. Cohorts with baseline LDL-C >100 mg/dL and familial hypercholesterolemia (FH) or CV event history (secondary prevention [SP]) were considered. Lifetime CV event rates were predicted either (1) using risk equations considering local risk factors (Spanish Familial Hypercholesterolemia Cohort Study) adjusted to reflect the increased risk of FH patients or (2) using CV event rates from local registries (Information System for the Development of Research in Primary Care) for SP patients. LDL-C relative reductions from evolocumab trials (Evolocumab 140 mg Q2W (bi-weekly) and 420 mg QM (monthly)) were converted into CV event reductions using rate ratios per millimole per liter (mmol/L; 38.67 mg/dL) from a meta-analysis of statin trials (Cholesterol Treatment Trialists' Collaboration). FINDINGS: Predicted 10-year/lifetime CV risks were 50%/95% (FH) and 62%/82% (SP) for SoC and 27%/83% (FH) and 44%/69% (SP) for evolocumab plus SoC. Predicted 10-year/lifetime major CV event risks were 42%/86% (FH) and 47%/67% (SP) for SoC and 21%/68% (FH) and 31%/52% (SP) for evolocumab plus SoC. Predicted per patient-year rates of non-fatal/fatal CV events were 2.2/0.8 (FH) and 1.1/0.6 (SP) for SoC and 1.2/0.6 (FH) and 0.7/0.5 (SP) for evolocumab plus SoC. Predicted CV event reductions per mmol/L were 17% (FH) and 15% (SP). Evolocumab treatment was associated with increased QALYs and costs compared with SoC (FH: ∆cost, €65,369; ∆QALY, 2.12; incremental cost-effectiveness ratio [ICER], €30,893; SP: ∆cost, €42,266; ∆QALY, 0.93; ICER, €45,340). IMPLICATIONS: Evolocumab plus to SoC may provide a cost-effective option for LDL-C lowering in FH and SP patients in Spain.

Longitudinal treatment patterns among US patients with atherosclerotic cardiovascular disease or familial hypercholesterolemia initiating lipid-lowering pharmacotherapy.

BACKGROUND: The most recent American College of Cardiology-American Heart Association guidelines recommend high-dose statin therapy for most patients with confirmed atherosclerotic cardiovascular disease (ASCVD) and patients with high cardiovascular risk. There is limited information regarding long-term treatment patterns among these patients. OBJECTIVE: To examine longitudinal treatment modifications in patients with ASCVD or familial hypercholesterolemia (FH). METHODS: This retrospective analysis of administrative claims data identified patients initiating statin or ezetimibe therapy between January 1, 2007, and December 31, 2012, who had evidence of ASCVD or FH. Patients were followed for up to 3 years and up to 4 treatment episodes. After initial treatment, subsequent treatment episodes began on the date of a treatment modification, which included discontinuation, statin dose change, switching, and augmentation. RESULTS: A total of 92,621 patients (mean age 64.7 years, 57.3% male) were identified; 91,740 had ASCVD, 937 had FH (56 had both). Most ASCVD (89.6%) and FH (85.8%) patients initiated on statin monotherapy. The most common treatment modification in the first treatment episode was discontinuation (ASCVD: 42.0%; FH: 58.4%); among patients who discontinued, most reinitiated therapy (70.5% of ASCVD, 76.8% of FH). Most ASCVD (68.2%) and FH (71.1%) patients initiated on moderate-dose statins; statin dose increase occurred in 10.3% of ASCVD and 18.5% of FH patients in the first episode. CONCLUSION: Among patients with high cardiovascular risk, most initiated on moderate-dose statins with infrequent uptitration. In light of the recent American College of Cardiology-American Heart Association guidelines, statin initiation practices will need to change to ensure appropriate therapy for high-risk patients.

Productivity losses associated with cardiovascular disease: a systematic review.

INTRODUCTION: People with cardiovascular disease (CVD) often require time off work to recover from illness or surgery; for example, following a myocardial infarction (MI) or stroke. These individuals incur income losses, work-related productivity is reduced for employers, and output is reduced for the wider economy. Productivity impacts to the economy also arise due to CVD-related mortality. Areas covered: A systematic literature review was conducted to identify and collate studies that report the magnitude of work-related productivity losses associated with CVD generally or specific cardiovascular (CV) events or conditions (coronary heart disease, MI, stroke, transient ischemic attack, angina, heart failure, peripheral artery disease, coronary revascularization). The search was conducted using Medline, Embase, the Cochrane Library, and Google to find studies published from January 2004 to January 2015. In total, 60 studies were identified, including 20 studies conducted in the USA, 25 studies conducted in Europe, and 18 studies conducted in other countries (three studies were conducted in multiple regions). The studies differed by the scope of losses assessed (absenteeism, presenteeism, early retirement, premature mortality) and CVD conditions/events included. Studies reported either average patient or population losses, and generally used a human capital rather than friction cost method. Outcomes were standardized and adjusted to 2015 US dollars where possible. Expert commentary: The review demonstrates that CVD imposes substantial morbidity- and mortality-related productivity costs. The studies identified in the review may be used to inform and populate societal economic evaluations in CVD, with the most appropriate source study being that most closely matching the context of the evaluation.

Systematic Review of Low-Density Lipoprotein Cholesterol Apheresis for the Treatment of Familial Hypercholesterolemia.

BACKGROUND: Apheresis is an important treatment for reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). We systematically reviewed the current literature surrounding LDL-C apheresis for FH. METHODS AND RESULTS: Electronic databases were searched for publications of LDL-C apheresis in patients with FH. Inclusion criteria include articles in English published in 2000-2013 that provide descriptions of practice patterns, efficacy/effectiveness, and costs related to LDL-C apheresis in patients with FH. Data were stratified by country and FH genotype where possible. Thirty-eight studies met the inclusion criteria: 8 open-label clinical trials, 11 observational studies, 17 reviews/guidelines, and 2 health technology assessments. The prevalence of FH was not well characterized by country, and underdiagnosis was a barrier to FH treatment. Treatment guidelines varied by country, with some guidelines recommending LDL-C apheresis as first-line treatment in patients with homozygous FH and after drug therapy failure in patients with heterozygous FH. Additionally, guidelines typically recommended weekly or biweekly LDL-C apheresis treatments conducted at apheresis centers that may last 2 to >3 hours per session. Studies reported a range for mean LDL-C reduction after apheresis: 57-75% for patients with homozygous FH and 58-63% for patients with heterozygous FH. Calculated annual costs (in US$2015) may reach US$66 374 to US$228 956 per patient for weekly treatment. CONCLUSIONS: LDL-C apheresis treatment may be necessary for patients with FH when drug therapy is inadequate in reducing LDL-C to target levels. While apheresis reduces LDL-C, high per-session costs and the frequency of guideline-recommended treatment result in substantial annual costs, which are barriers to the optimal treatment of FH.

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.

Medical costs associated with cardiovascular events among high-risk patients with hyperlipidemia.

OBJECTIVES: This study descriptively examined acute and longer term direct medical costs associated with a major cardiovascular (CV) event among high-risk coronary heart disease risk-equivalent (CHD-RE) patients. It also gives a firsthand look at fatal versus nonfatal CV events. METHODS: The MarketScan(®) Commercial Claims and Encounters Database was used to identify adults with a CV event in 2006-2012 with hyperlipidemia or lipid-lowering therapy use in the 18 months prior to one of the following inpatient CV events: myocardial infarction, ischemic stroke, unstable angina, transient ischemic attack, percutaneous coronary intervention, or coronary artery bypass graft (CABG). Patients were required to have a preindex diagnosis of at least one of the following: peripheral arterial disease, abdominal aortic aneurysm, carotid artery disease, or diabetes. A subset analysis was conducted with patients with data linkable to the Social Security Administration Master Death File. Direct medical costs were reported for each quarter following a CV event, for up to 36 months after the first CV event. RESULTS: In total, 38,609 CHD-RE patients were included, mean age 57 years, 31% female. CABG, myocardial infarction, and percutaneous coronary intervention were the most frequent and most expensive first CV events, accounting for >75% of all first CV events with mean first quarter costs ranging from $17,454 (nonfatal transient ischemic attack) to $125,690 (fatal CABG). Overall, 15% of those with a first CV event went on to have a second event during the 36-month study period with mean first quarter nonfatal and fatal costs similar to first event levels. Third CV events were rare, happening in less than 3% of patients. CONCLUSION: CV events among CHD-RE patients were costly regardless of sequence, averaging $47,433 in the first 90 days following an event and remaining high, never returning to preevent levels. When fatal, first CV event costs were 1.2 to 2.9 times higher than when nonfatal.

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.

Tumor necrosis factor-blocker dose escalation in rheumatoid arthritis patients in a pharmacy benefit management setting.

INTRODUCTION: Dose escalation with tumor necrosis factor (TNF)-blockers is poorly characterized in pharmacy benefit management (PBM) settings. METHODS: This retrospective study used integrated pharmacy and medical claims from the PBM Medco to characterize dose escalation among rheumatoid arthritis (RA) patients treated with etanercept and adalimumab. Data from adults with RA with pharmacy claims for etanercept or adalimumab between 1/1/2007 and 12/31/2009 and continuous enrollment for ≥ 6 months before and ≥ 12 months after first (index) pharmacy claim were analyzed. "New" patients had no claim for TNF-blocker in the 6 months prior to receipt of their index TNF-blocker; otherwise, they were classified as "continuing" patients. Endpoints included 12-month persistence and duration on index medication and dose escalation. Dose escalation (allowed per adalimumab label but not for etanercept) in patients' persistent ≥ 12 months was estimated using five methods: (1) average weekly dose ≥ 110% of recommended label dose; (2) average subsequent dose ≥ 130% of starting dose; (3) last dose ≥ 110% of starting dose; (4) ≥ 2 consecutive instances of dose ≥ 130% of starting dose; and (5) any instance where dose increase connoted an additional syringe/vial use. RESULTS: Data from 1,260 patients on etanercept and 852 patients on adalimumab were analyzed; 45.3 and 45.9% of new patients on etanercept and adalimumab, respectively, and 60.5 and 60.8% of continuing patients had ≥ 12 months persistence on index medication. Across all five methods used to estimate dose escalation, patients receiving etanercept had significantly lower rates of dose escalation (P < 0.001) than patients receiving adalimumab. For new patients, rates of dose escalation were 0.4-1.2% for etanercept and 8.3-14.1% for adalimumab. For continuing patients, rates ranged from 1.1 to 2.9% for etanercept and 7.0-28.3% for adalimumab. CONCLUSIONS: New and continuing patients from this PBM database on etanercept had significantly lower rates of dose escalation than patients on adalimumab.

Impact of etanercept on work and activity impairment in employed moderate to severe rheumatoid arthritis patients in the United States.

OBJECTIVE: To quantify the impact of etanercept on work and activity impairment in employed US patients with moderate to severe rheumatoid arthritis (RA). METHODS: This prospective, observational, longitudinal study recruited RA patients initiating etanercept (50 mg/week) between January 2009 and March 2010. The Work Productivity and Activity Impairment Questionnaire (WPAI) and domestic productivity questionnaire were administered by telephone interviews at baseline and at 1, 2, 3, and 6 months after etanercept initiation. The human capital approach was used to estimate the costs of work impairment. Changes in WPAI measures were analyzed using Wilcoxon's signed rank test. RESULTS: RA patients (n = 204) initiating etanercept were a mean ± SD age of 46.6 ± 10.9 years and 72% were women. After 6 months, 153 patients continued treatment (continuers) and showed significant decreases in overall work impairment (41.9% at baseline versus 25.2% at 6 months; P < 0.0001), absenteeism (8.4% versus 2.3%; P = 0.0001), presenteeism (38.9% versus 24.3%; P < 0.0001), and activity impairment (55.7% versus 30.9%; P < 0.0001) and a 76.4% reduction in work hours lost weekly due to RA (3.2 versus 0.8; P = 0.0001). The projected 12-month gain in work productivity for continuers was 284.5 hours per patient, equating to $3,233-22,533 depending on annual income level, which partially or completely offset the annual cost of etanercept ($20,190). Domestic productivity improved from 41.5% at baseline to 69.6% at 6 months (P < 0.0001). CONCLUSION: In US employed moderate to severe RA patients, etanercept led to significant reductions in overall work and activity impairment; the value of increased work productivity partially or completely offset the cost of treatment.

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 with etanercept and adalimumab for psoriatic diseases in a real-world setting.

BACKGROUND: This study examined real-world etanercept and adalimumab treatment patterns in patients with psoriasis, psoriatic arthritis, or both. METHODS: This retrospective analysis utilized data from patients with psoriasis, psoriatic arthritis, or both from a large, US claims database. Outcome measures included persistence on index therapy; pauses (7-59 days) and gaps (≥60 days) in therapy; and rates of discontinuing, switching and restarting index therapy in nonpersistent patients. RESULTS: Of 4,453 patients, 2,534 initiated etanercept and 1,919 initiated adalimumab. In psoriasis patients (n = 2,775), 46.4% and 56.8% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 49.0% and 56.3% discontinued, 23.8% and 22.4% restarted and 14.9% and 11.3% switched index therapy within 12 months. In psoriatic arthritis patients (n = 1,197), 60.7% and 63.3% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 48.3% and 51.6% discontinued, 25.8% and 20.0% restarted and 16.5% and 17.9% switched index therapy. In patients with both (n = 481), 58.1% and 59.6% on etanercept and adalimumab, respectively, were persistent for ≥12 months, 42.7% and 63.2% discontinued, 24.3% and 12.6% restarted and 21.4% and 15.8% switched index therapy. CONCLUSIONS: Treatment modifications were common in patients with psoriasis, psoriatic arthritis, or both within 12 months of initiating etanercept or adalimumab.

Psoriasis treatment patterns with etanercept and adalimumab in a United States health plan population.

BACKGROUND: A retrospective study utilizing administrative claims from a US commercial health plan was performed to examine etanercept and adalimumab treatment patterns among patients with psoriasis (PSO). METHODS: Biologic-naïve PSO patients initiating etanercept or adalimumab therapy between 18 January 2008 and 31 December 2008 were identified. Patients continuously enrolled in the health plan for 6 months before and ≥12 months after therapy initiation were followed until disenrollment from the plan or 31 December 2009. Persistence was defined as continuous use of index TNF blocker without a gap in therapy ≥60 days. Patients with gaps in index therapy ≥60 days were classified as discontinuing, switching, or restarting the index therapy. RESULTS: In total, 497 patients initiated etanercept and 330 the adalimumab therapy. Mean age for both groups was 43 years. Approximately 40-42% of patients were persistent on their index TNF blocker for 1 year. Among patients with a ≥60-day gap in therapy, discontinuation without restart or switch occurred in 37% of etanercept and 45% of adalimumab patients (p = 0.04). Differences in therapy restart or switching between the groups were not statistically significant. CONCLUSIONS: TNF-blocker therapy persistence is low among PSO patients in this health plan. More than one-third of patients restarted their index TNF blocker after a gap in therapy.

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.

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.

Transfusion burden in non-dialysis chronic kidney disease patients with persistent anemia treated in routine clinical practice: a retrospective observational study.

BACKGROUND: Transfusion patterns are not well characterized in non-dialysis (ND) chronic kidney disease (CKD) patients. This study describes the proportion of patients transfused, units of blood transfused and trigger-hemoglobin (Hb) levels for transfusions in severe anemic, ND-CKD patients in routine practice. METHODS: A retrospective cohort study of electronic medical record data from the Henry Ford Health System identified 374 adult, ND-CKD patients with severe anemia (Hb < 10 g/dL and subsequent use of erythropoiesis-stimulating agents [ESA] therapy, blood transfusions, or a second Hb < 10 g/dL) between January 2004 and June 2008. Exclusions included those with prior diagnoses of cancer, renal or liver transplant, end-stage renal disease, acute bleeding, trauma, sickle cell disease, or aplastic anemia. A gap of ≥ 1 days between units of blood transfused was counted as a separate transfusion. RESULTS: At least 1 transfusion (mean of 2 units; range, 1-4) was administered to 20% (75/374) of ND-CKD patients with mean (± SD) follow-up of 459 (± 427) days. The mean (± SD) Hb level closest and prior to a transfusion was 8.8 (± 1.5) g/dL. Patients who were hospitalized in the 6 months prior to their first anemia diagnosis were 6.3 times more likely to receive a blood transfusion than patients who were not hospitalized (p < 0.0001). Patients with peripheral vascular disease (PVD) were twice as likely to have a transfusion as patients without PVD (p = 0.04). CONCLUSIONS: Transfusions were prevalent and the trigger hemoglobin concentration was approximately 9 g/dL among ND-CKD patients with anemia. To reduce the transfusion burden, clinicians should consider other anemia treatments including ESA therapy.

Annual costs of tumor necrosis factor inhibitors using real-world data in a commercially insured population in the United States.

OBJECTIVE: To calculate annual cost per treated patient of tumor necrosis factor (TNF) inhibitors etanercept, adalimumab, and infliximab for common approved indications, based on actual TNF-inhibitor use in clinical practice. METHODS: Adults with ≥1 claim for etanercept, adalimumab, or infliximab between January 2005 and March 2009 were identified from the IMS LifeLink™ Health Plan Claims Database. Patients new to therapy or continuing therapy (i.e., a prior claim for a TNF-inhibitor) were analyzed separately. Included patients had been enrolled from 180 days before the first TNF-inhibitor claim (index date) through 360 days after the index date and had a diagnosis during the pre-index period for rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. Patients with Crohn's disease, ulcerative colitis, or juvenile idiopathic arthritis were excluded. Annual costs were calculated using wholesale acquisition costs for the TNF-inhibitor and Medicare Physician Fee Schedule for drug administration. Costs from restarting or switching TNF-inhibitor therapy during the first year were included. RESULTS: A total of 27,704 patients (11,528 new, 16,176 continuing) had claims for etanercept, adalimumab, or infliximab, most commonly (65%) for treatment of rheumatoid arthritis. The most commonly used agent was etanercept (14,777 patients; 53%), followed by adalimumab (6862 patients; 25%) and infliximab (6065 patients; 22%). Annual cost per treated patient was etanercept $14,873, adalimumab $17,766, and infliximab $21,256 across all indications. Annual cost per treated patient by disease was (etanercept/adalimumab/infliximab): rheumatoid arthritis ($14,314/$17,700/$20,390), psoriasis ($17,182/$17,682/$23,935), psoriatic arthritis ($15,030/$18,483/$24,974), and ankylosing spondylitis ($14,254/$16,925/$23,056). New and continuing patients showed similar results, with etanercept having the lowest costs. LIMITATIONS: This analysis is limited to three TNF-inhibitors and a US managed-care population. CONCLUSIONS: Based on this analysis of real-world use of TNF-inhibitors among patients in nationwide clinical practice settings, the annual TNF-inhibitor cost per treated patient was lowest for etanercept across all indications.

Darbepoetin alfa impact on health status in diabetes patients with kidney disease: a randomized trial.

BACKGROUND AND OBJECTIVES: Quality of life (QOL) is markedly impaired in patients with anemia, diabetes mellitus, and chronic kidney disease. Limited data exist regarding the effect of anemia treatment on patient perceptions. The objectives were to determine the longitudinal impact of anemia treatment on quality of life in patients with diabetes and chronic kidney disease and to determine the predictors of baseline and change in QOL. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a large, double blind study, patients with type 2 diabetes mellitus, nondialysis chronic kidney disease (estimated GFR, 20 to 60 ml/min per 1.73 m(2)), and anemia (hemoglobin 10.4 g/dl) were randomized to darbepoetin alfa or placebo. QOL was measured with Functional Assessment of Cancer Therapy-Fatigue, Short Form-36, and EuroQol scores over 97 weeks. RESULTS: Patients randomized to darbepoetin alfa reported significant improvements compared with placebo patients in Functional Assessment of Cancer Therapy-Fatigue, and EuroQol scores visual analog scores, persisting through 97 weeks. No consistent differences in Short Form-36 were noted. Consistent predictors of worse change scores include lower activity level, older age, pulmonary disease, and duration of diabetes. Interim stroke had a substantial negative impact on fatigue and physical function. CONCLUSION: Darbepoetin alfa confers a consistent, but small, improvement in fatigue and overall quality of life but not in other domains. These modest QOL benefits must be considered in the context of neutral overall effect and increased risk of stroke in a small proportion of patients. Patient's QOL and potential treatment risk should be considered in any treatment decision.