Economic burden during remission and after relapse among older patients with newly diagnosed acute myeloid leukemia without hematopoietic stem cell transplant: A retrospective study using the SEER-Medicare database.

Acute myeloid leukemia (AML) is associated with a substantial clinical and economic burden. This study characterized the magnitude of this burden following initial treatment with standard or less intensive therapies (hypomethylating agents [HMAs]) and throughout different treatment phases post-remission. The Surveillance, Epidemiology, and End Results (SEER) cancer registry (2007-2016) linked with Medicare beneficiary claims (2007-2015) was analyzed. Patients were ≥ 65 years old with AML who initiated chemotherapy or HMAs and achieved remission. Outcomes included baseline characteristics, treatment patterns, clinical outcomes, healthcare resource utilization (HRU), and costs (2019 United States dollar). Economic impacts were stratified by treatment phase (initial treatment, early post-remission, late post-remission, and post-relapse). Early and late post-remission were defined as treatment initiated ≤ 60 days and > 60 days following initial treatment, respectively. A subgroup analysis of patients receiving only HMAs as initial treatment was also conducted. Overall, 530 patients were included (mean age: 74.1 years; 53.6 % male). In the overall analysis, 68.1 % of patients received post-remission treatment; 31.9% had no post-remission treatment. Mean monthly per patient healthcare costs by treatment phase were $45,747 (initial treatment), $30,248 (early post-remission), $23,173 (late post-remission), and $37,736 (post-relapse), driven predominantly by inpatient visits. The HMA subgroup analysis comprised 71 patients (mean age: 78.8 years; 50.7 % male); mean monthly per patient healthcare costs were highest post-relapse. The economic burden of AML among older patients is substantial across all treatment phases. AML treatments that induce and prolong remission may reduce HRU and the economic burden of disease.

Treatment patterns and overall survival of patients with double-class and triple-class refractory multiple myeloma: a US electronic health record database study.

Patients with relapsed/refractory multiple myeloma (RRMM) resistant to multiple drug classes remain a high unmet need population. This longitudinal retrospective cohort study assessed real-world treatment patterns and outcomes in adults with RRMM. Patients who had three or more prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (double-exposed) were further categorized as refractory to a PI and an immunomodulatory agent (double-class refractory, n = 381) or additionally to an anti-CD38 monoclonal antibody (triple-class refractory, n = 173). Treatment options are limited for patients with double-class or triple-class refractory disease. Retreatment is a part of standard of care. Bortezomib and lenalidomide had the highest retreatment rates among double-class and triple-class refractory patients. Survival outcomes remain poor among RRMM patients with median overall survival (OS) of 22.3 and 11.6 months for double-class refractory and triple-class refractory patients, respectively. This study highlights the need for novel efficacious therapies in this heavily pretreated RRMM population.

Real-world clinical burden among patients with and without heart failure worsening after cardiac resynchronization therapy.

OBJECTIVE: Cardiac resynchronization therapy (CRT) can improve cardiac function in patients with heart failure (HF); however, in some patients, HF worsens despite CRT. This study characterized the long-term clinical burden of patients with and without HF worsening (HFW) within 6 months post CRT implantation. METHODS: A claims database (2007-2018) was used to identify two cohorts of adults: those with HFW within 180 days post-CRT and those with no HFW (NHFW). The evaluated clinical outcomes were cardiovascular events/complications, HF-related interventions, hospice enrollment, and all-cause mortality. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders; adjusted comparisons were assessed using weighted Cox proportional hazard ratios (HRs). RESULTS: Among the 12,753 adults analyzed (HFW: N = 4,785; NHFW: N = 7,968), the mean age was 72 years and the mean duration of follow-up was approximately 2 years. The clinical burden was greater for HFW than for NHFW in terms of all-cause mortality (19.7% vs. 12.1%) and occurrence of atrial fibrillation (57.4% vs. 51.2%). In the IPTW-adjusted Cox proportional hazard analyses, patients with HFW had a 54% higher average hazard of experiencing all-cause mortality compared to NHFW (adjusted average HR = 1.54, 95% confidence interval [CI]: 1.41-1.70; p < .001). Of the clinical events experienced by ≥5% of patients, the greatest differences in average hazard were for HF decompensation (adjusted average HR = 1.83, 95% CI: 1.60-2.09) and HF decompensation or death (HR = 1.63, 95%CI: 1.50-1.77). CONCLUSION: Patients with early HFW post-CRT experienced a significantly higher clinical burden than those without HFW. Vigilance for signs of worsening HF in the first 6 months post-CRT is warranted.

Indirect comparison of apomorphine sublingual film and levodopa inhalation powder for Parkinson's disease 'OFF' episodes.

Aim: To compare efficacy of apomorphine sublingual film (APL) and levodopa inhalation powder (CVT-301) for 'on-demand' treatment of Parkinson's disease 'OFF' episodes. Patients & methods: Patient-level data from an APL pivotal study were re-weighted to match average baseline characteristics from a CVT-301 study (SPAN-PD). Placebo-adjusted treatments were compared at week 12. Results: Improvements in predose Unified Parkinson's Disease Rating Scale Part III scores were significantly larger for APL versus CVT-301 at 60 min postdose (least squares mean difference-in-difference: -8.82; p = 0.002); difference at 30 min favored APL but was not statistically significant (-4.46; p = 0.103). Total daily 'OFF' time reductions were significantly larger for APL versus CVT-301 (-1.31 h; p = 0.013). Conclusion: Results suggest APL treatment may lead to improved efficacy versus CVT-301.

The Economic Burden of Thromboembolic Events Among Patients with Immune-Mediated Diseases.

INTRODUCTION: Thromboembolic events (TEs) are associated with considerable costs. However, there is a paucity of evidence quantifying the economic burden associated with TEs among patients with immune-mediated diseases (IMDs). METHODS: This retrospective cohort study used the IBM MarketScan® Commercial and Medicare Supplemental Claims databases (2014-2018). Commercially insured adults with IMDs were classified into two cohorts based on diagnosis of TEs (deep vein thrombosis, pulmonary embolism, ischemic stroke, myocardial infarction). Patients in the TE cohort were matched on type of IMD, age, sex, and year of diagnosis to patients in the no TE cohort. In the TE cohort, the index date was the date of first TE following first IMD diagnosis. In the no TE cohort, the index date was assigned so the duration from first IMD diagnosis to index date matched the duration for the corresponding patient in the TE cohort. All-cause total healthcare costs were compared between cohorts in the 30-day and 1-year periods following the index date (inclusive). Unadjusted comparisons were conducted using Wilcoxon signed-rank tests. Adjusted results were estimated using generalized estimating equations with robust sandwich estimator. RESULTS: Overall, 9681 matched patients were included in each cohort (mean age 61.1 years; 63.7% female). The TE cohort had higher proportions of comorbidities than the no TE cohort (Charlson Comorbidity Index [1.5 vs. 0.9]; p < 0.0001). Adjusted all-cause total healthcare costs were significantly greater in the TE cohort versus no TE cohort in the 30-day and 1-year periods following the index date (cost difference: 30-day, $17,574; 1-year, $36,459; both p < 0.0001) and were driven by inpatient costs (cost difference: 30-day, $14,864; 1-year, $23,360; both p < 0.0001). TE-related healthcare costs were $15,955 and $20,239 in the 30-day and 1-year periods, respectively. CONCLUSION: Among patients with IMDs, TEs are associated with substantial economic burden within 30-days and 1-year following the event.

Risk of Thromboembolic Events and Associated Healthcare Costs in Patients with Inflammatory Bowel Disease.

INTRODUCTION: Inflammatory bowel disease (IBD) is associated with greater risk of thromboembolic events (TEs) due to the link between systemic inflammation and hypercoagulability. This study assessed the rates of TEs among patients with IBD versus patients without immune-mediated disease (IMD) and the cost of TEs among patients with IBD in the United States. METHODS: This study used the IBM MarketScan® Commercial and Medicare Supplemental Databases (2014-2018). To assess the incremental rates of TEs (deep vein thrombosis [DVT], pulmonary embolism [PE], ischemic stroke [IS], myocardial infarction [MI]), patients with IBD were matched to patients without IMD. Unadjusted and adjusted incidence rate ratios (IRRs) of TEs were used to compare cohorts. To assess the cost of TEs, patients with IBD with TEs were matched to patients with IBD without TEs. Costs were assessed 30 days and 1 year post index date. RESULTS: There were 34,687 matched pairs included in the rates of TE analyses. Compared to patients without IMD, patients with IBD had greater rates of DVT (adjusted IRR [95% confidence interval] 2.44 [2.00, 2.99]; p < 0.01) and PE (1.90 [1.42, 2.54]; p < 0.01). Increased rates were not observed for IS and MI. There were 1885 matched pairs included in the cost of TE analyses. Patients with IBD with TEs incurred greater healthcare costs over 30 days and 1 year versus patients without TEs (adjusted total cost difference: 30 days $20,784; 1 year $44,630; p < 0.01 for both). CONCLUSIONS: Patients with IBD experienced greater rates of DVT and PE compared to patients without IMD; this elevated risk was associated with a substantial economic burden.

The Impact of Antipsychotic Dose Reduction on Clinical Outcomes and Health Care Resource Use Among Medicare Patients with Schizophrenia.

BACKGROUND: Antipsychotic medications are used to treat schizophrenia and may be associated with adverse effects, including tardive dyskinesia (TD), following prolonged use or upon changes in dosing regimen. OBJECTIVE: This retrospective analysis evaluated the burden of antipsychotic dose reduction in Medicare patients with schizophrenia. METHODS: This matched cohort study used Medicare claims data (2006-2017) analyzed for patients with schizophrenia and two or more claims for antipsychotics, with one or more antipsychotic monotherapy period ≥ 90 days. Cohorts were defined for patients with antipsychotic dose reductions ≥ 10% and stable doses. A separate analysis was conducted using patients with dose reductions ≥ 30%. Outcomes included all-cause emergency room (ER) visits, all-cause inpatient visits, schizophrenia relapse, other psychiatric relapse, and TD diagnosis. Covariates included age, disease duration, comorbidities, and medication use. RESULTS: The analysis included 276,030 patients with ≥ 10% dose reductions and 211,575 patients with ≥ 30% dose reductions. Patient characteristics were balanced between cohorts. Patients with ≥ 10% or ≥ 30% dose reductions had a shorter time to ER visit, inpatient visit, schizophrenia relapse, other psychiatric relapse, and TD diagnosis versus those receiving stable doses (all p < 0.001). Significance was maintained when unmatched baseline characteristics were adjusted. CONCLUSIONS: Patients with antipsychotic dose reductions may be at risk for increased ER visits, increased hospitalizations, and significant unfavorable mental health-related clinical outcomes, suggesting that dose reduction may increase overall health care burden in some patients with schizophrenia. This work highlights the need for alternative strategies in the management of patients with TD.

Risk of Thromboembolic Events and Associated Risk Factors, Including Treatments, in Patients with Immune-mediated Diseases.

PURPOSE: This study assessed the association between thromboembolic events (TEs) and immune-mediated diseases (IMDs) and characterized the risk profile of TEs among patients with IMDs. METHODS: An administrative claims database (2014-2018) was used to identify adults with ≥2 diagnoses on different dates for ≥1 IMD (IMD cohort; ankylosing spondylitis, atopic dermatitis, inflammatory bowel disease, multiple sclerosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, and systemic lupus erythematosus); patients without an IMD diagnosis were assigned to the non-IMD cohort. Patients in the IMD cohort were matched 1:1 to patients in the non-IMD cohort on age, sex, and index date. Incremental risk of TE (ie, deep vein thrombosis [DVT], pulmonary embolism [PE], myocardial infarction [MI], and ischemic stroke [IS]) was assessed using adjusted incidence rate ratios (aIRRs) to control for covariates in both cohorts. Risk factors for TEs were assessed in the IMD cohort and included age, female sex, comorbidities, baseline TEs, non-IMD treatments, and IMD treatments. FINDINGS: A total of 182,431 patients were included in each cohort (mean age, [51.3] years; 64.3% female). A higher proportion of patients in the IMD cohort versus the non-IMD cohort had ≥1 baseline TE (4.1% vs 2.7%; P < 0.0001). The IMD cohort had a 1.80 (95% CI, 1.68-1.92; P < 0.0001) times higher rate of TEs versus patients in the non-IMD cohort. After adjustments, patients in the IMD cohort had a 1.49 (95% CI, 1.40-1.59; P < 0.0001) times higher rate of TEs versus patients in the non-IMD cohort. Similar results were observed across individual TEs (DVT: aIRR = 1.78; PE: aIRR = 1.66; MI: aIRR = 1.17; IS: aIRR = 1.35; all P < 0.05). Risk factor profiles varied by TE. The greatest risk factor was respective TE during baseline (eg, patients with baseline DVT had 41.1 times the rate of DVT during the study period vs patients without baseline DVT; P < 0.001). Comorbidities, such as cardiovascular diseases, type 2 diabetes, and peripheral vascular disease, were associated with increased rates of MI (IRR = 2.60, 1.30, and 1.54, respectively; all P < 0.05) and IS (IRR = 1.53, 1.54, and 1.24, respectively; all P < 0.05). Janus kinase inhibitors were associated with an increased rate of PE (IRR = 2.52; P < 0.05) and nonsignificant, numerically higher rates of DVT (IRR = 1.23; P = NS) and IS (IRR = 1.82; P = NS). Sphingosine 1-phosphate receptor modulators were associated with decreased rates of TEs (DVT: IRR = 0.61, P = NS; PE: IRR = 0.30, P = NS; MI: IRR = 0.54, P = NS; IS: IRR = 0.33, P < 0.05). IMPLICATIONS: The risk of TEs was higher among patients with IMD versus patients without IMD; several factors may affect this risk.

Real-world migraine-related healthcare resource utilization and costs associated with improved vs. worsened/stable migraine: a panel-based chart review in France, Germany, Italy, and Spain.

OBJECTIVE: To estimate the migraine-related healthcare resource utilization (HRU) and costs among patients with improved vs. worsened/stable migraine. METHODS: This was a follow-up to a retrospective, panel-based chart review conducted in France, Germany, Italy, and Spain among a panel of physicians (neurologists, headache specialists, and pain specialists) who agreed to participate in patient studies and had treated ≥10 migraine patients in 2017. Eligible physicians extracted data for up to five adults with ≥4 monthly migraine days (MMDs) who initiated a preventive treatment on or after 1 January 2013 and received physician care for ≥6 months after the date of the most recent preventive treatment initiation (index date). Based on the trajectory of migraine severity from the 1-month pre-index period to the 6-month post-index period, cohorts were classified as improved (converting from chronic to episodic or from chronic/episodic to <4 MMDs) or stable/worsened (remaining chronic/episodic or transforming from episodic to chronic) migraine. Migraine-related HRU and costs (2017 €) during the 6-month post-index period were compared between patients with improved vs. stable/worsened migraine. RESULTS: Overall, 470 patient charts were analyzed, with 339 classified as improved migraine and 131 classified as stable/worsened migraine. After adjusting for within-physician correlation, country, sex, and presence of comorbidities before the index date, the improved migraine cohort had significantly fewer migraine-related physician office visits (-0.81; p < .001), emergency room/accident & emergency (ER/A&E) visits (-0.67; p < .001), and hospitalizations (-0.12; p < .001) in the 6-month post-index period vs. the stable/worsened migraine cohort. Consistent with HRU patterns, the adjusted migraine-related costs for physician office visits (-€42.23; p < .05), hospitalizations (-€215.56; p < .05), and total costs (-€396.81; p < .01) in the 6-month post-index period were significantly reduced for the improved migraine cohort vs. the stable/worsened migraine cohort. CONCLUSIONS: Over a 6-month period following initiation of preventive migraine treatment, patients with improved migraine had significantly lower migraine-related HRU and costs than those with stable/worsened migraine.

Correction: Burden of treatment-resistant depression in Medicare: A retrospective claims database analysis.

[This corrects the article DOI: 10.1371/journal.pone.0223255.].

Cost-Effectiveness of Apomorphine Sublingual Film as an "On-Demand" Treatment for "OFF" Episodes in Patients with Parkinson's Disease.

Background: "On-demand" treatments approved in the United States (US) for "OFF" episodes in Parkinson's disease (PD) include apomorphine hydrochloride injection (SC-APO), apomorphine sublingual film (APL), and levodopa inhalation powder (CVT-301). APL received US approval in 2020, and its cost-effectiveness has not been compared with SC-APO and CVT-301. Objective: To develop a cost-effectiveness analysis model comparing APL versus SC-APO and CVT-301 for treatment of patients with PD experiencing "OFF" episodes from a US payer perspective. Methods: The model estimated total costs and effectiveness for each comparator arm, informed from the treatments' pivotal studies or literature, over a 10-year horizon. Total and incremental patient costs (in 2020 US dollars), total time spent without "OFF" episode symptoms, and quality-adjusted life years (QALY) gained were summarized and compared. Incremental cost-effectiveness ratios for APL versus SC-APO and CVT-301 were estimated and expressed as incremental patient costs per patient QALY gained and incremental cost per "OFF" hour avoided. Scenario analyses varying inputs and including caregiver costs were also conducted. Results: In the base case, APL had the lowest total "on-demand" treatment costs ($42,095) compared with SC-APO ($276,320; difference: -$234,225) and CVT-301 ($69,577; difference: -$27,482) over the 10-year horizon. APL was also associated with the highest utility, with incremental QALYs of 0.019 versus SC-APO and 0.235 versus CVT-301. APL was dominant over CVT-301 in terms of incremental cost per "OFF" hour, and dominant over both CVT-301 and SC-APO in terms of incremental cost per QALY gained. In all scenario analyses, APL was dominant against both SC-APO and CVT-301, confirming the robustness of the base-case results. Discussion: APL was dominant compared with both comparator arms, being less costly and more effective on average than SC-APO and CVT-301 in terms of QALYs. For SC-APO, cost-effectiveness of APL was driven by lower "on-demand" treatment costs and adverse event-related disutilities. For CVT-301, cost-effectiveness of APL was driven by lower "on-demand" treatment costs and substantially higher efficacy. Conclusions: From a US payer perspective, APL represents a cost-effective option compared with SC-APO and CVT-301 for treatment of "OFF" episodes in patients with PD.

Real-World Economic Burden Among Patients With And Without Heart Failure Worsening After Cardiac Resynchronization Therapy.

INTRODUCTION: Although cardiac resynchronization therapy (CRT) has the potential to improve cardiac function in patients with heart failure (HF), a considerable portion of patients do not respond to therapy. This study assessed the economic burden among patients with and without HF worsening after receiving CRT in real-world practice. METHODS: In this retrospective claims-based study using Optum's de-identified Clinformatics® Data Mart Database (January 2007-December 2018), adults who received CRT were stratified into two cohorts based on whether they showed evidence of HF worsening within 180 days post-CRT implantation. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding, accounting for demographics (e.g., age, sex), the Quan-Charlson Comorbidity Index, other clinical characteristics, healthcare resource utilization (HRU), and healthcare costs during the 180 days pre-CRT (baseline period). Annualized all-cause and congestive HF-related HRU and healthcare costs from payer and patient perspectives were assessed from day 181 post-CRT (follow-up period), and compared between cohorts using incidence rate ratios (IRRs) and cost ratios (CRs). RESULTS: This study included 12,753 patients (n = 4785 with HF worsening; n = 7968 without). Mean age was 72 years and roughly two-thirds were male. Baseline characteristics were balanced between cohorts post-IPTW. During follow-up, patients with HF worsening had significantly greater annual all-cause inpatient [adjusted IRR (95% confidence interval) = 1.55 (1.44, 1.66), p < 0.001], outpatient [adjusted IRR = 1.46 (1.32, 1.61), p < 0.001], and emergency department [adjusted IRR = 1.31 (1.22, 1.41), p < 0.001] visits. Mean annual total per patient payer-paid amounts were significantly higher for patients with HF worsening versus without HF worsening [adjusted CR = 1.68 (1.56, 1.80), p < 0.001]. Annual patient-paid medical costs were also higher for patients with HF worsening [adjusted CR = 1.31 (1.25, 1.38), p < 0.001]. Results were similar for congestive HF-related HRU and costs. CONCLUSIONS: The incremental economic burden among patients with HF worsening following CRT is substantial. Efforts aimed at CRT optimization may help reduce this burden.

Burden of treatment-resistant depression in Medicare: A retrospective claims database analysis.

BACKGROUND: Previous studies have assessed the incremental economic burden of treatment-resistant depression (TRD) versus non-treatment-resistant major depressive disorder (i.e., non-TRD MDD) in commercially-insured and Medicaid-insured patients, but none have focused on Medicare-insured patients. OBJECTIVE: To assess healthcare resource utilization (HRU) and costs of patients with TRD versus non-TRD MDD or without major depressive disorder (MDD; i.e., non-MDD) in a Medicare-insured population. METHODS: Adult patients were retrospectively identified from the Chronic Condition Warehouse de-identified 100% Medicare database (01/2010-12/2016). MDD was defined as ≥1 MDD diagnosis and ≥1 claim for an antidepressant. Patients initiated on a third antidepressant following two antidepressant treatment regimens of adequate dose and duration were considered to have TRD. The index date was defined as the date of the first antidepressant claim for the TRD and non-TRD MDD cohorts, and as a randomly imputed date for the non-MDD cohort. Patients with TRD were matched 1:1 to non-TRD MDD patients and randomly selected non-MDD patients based on propensity scores. Analyses were also performed for a subset of patients aged ≥65. RESULTS: Of 29,543 patients with MDD, 3,225 (10.9%) met the study definition of TRD; 157,611 were included in the non-MDD cohort. Matched patients with TRD and non-TRD MDD were, on average, 58.9 and 59.0 years old, respectively. The TRD cohort had higher per-patient-per-year (PPPY) HRU than the non-TRD MDD (e.g., inpatient visits: incidence rate ratio [IRR] = 1.36) and non-MDD cohorts (e.g., inpatient visits: IRR = 1.84, all P<0.001). The TRD cohort had significantly higher total PPPY healthcare costs than the non-TRD MDD cohort ($25,517 vs. $20,425, adjusted cost difference = $3,385) and non-MDD cohort ($25,517 vs. $14,542, adjusted cost difference = $4,015, all P<0.001). Similar results were found for the subset of patients ≥65. CONCLUSION: Among Medicare-insured patients, those with TRD had higher HRU and costs compared to those with non-TRD MDD and non-MDD.

Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials.

INTRODUCTION: This study estimated the minimal clinically important difference (MCID) for Mini Mental State Examination, Clinical Dementia Rating Scale sum of boxes, and Functional Activities Questionnaire across the Alzheimer's disease (AD) spectrum. METHODS: Retrospective analysis of the National Alzheimer's Coordinating Center Uniform Data Set (9/2005-9/2016) and MCID for clinical outcomes were estimated using anchor-based (clinician's assessment of meaningful decline) and distribution-based (1/2 baseline standard deviation) approaches, stratified by severity of cognitive impairment. RESULTS: On average, a 1-3 point decrease in Mini Mental State Examination, 1-2 point increase in Clinical Dementia Scale sum of boxes, and 3-5 point increase in Functional Activities Questionnaire were indicative of a meaningful decline. The MCID values generally increased by disease severity; the effect size and standardized response mean for those with meaningful decline were consistently in the acceptable ranges for MCID. DISCUSSION: These findings can inform design and interpretation of future clinical trials.

Real-world healthcare resource utilization related to migraine treatment failure: a panel-based chart review in France, Germany, Italy, and Spain.

Aims: This retrospective chart review examined the six-month migraine-related healthcare resource use (HRU) among European patients who had ≥4 migraine days per month and previously failed at least two prophylactic migraine treatments. Methods: Neurologists, headache specialists, and pain specialists in France, Germany, Italy, and Spain who treated ≥10 patients with migraine in 2017 were recruited (April-June 2018) to extract anonymized patient-level data. Eligible physicians randomly selected charts of up to five adult patients with clinically-confirmed migraine, ≥4 migraine days in the month prior to the index date, and had previously failed at least two prophylactic migraine treatments. Treatment failure was defined as discontinuation due to lack of efficacy and/or tolerability. Demographic and disease characteristics as of the index date, and migraine-related HRU incurred during the 6-month study period, were recorded. Results: A total of 104 physicians contributed 168 charts for patients (63% female). On average, patients were 38 years old and failed 2.3 prophylactic treatments as of the index date. During the study period, 83% of patients had ≥1 outpatient visit for migraine in the physician's office, and 27% went to the ER/A&E. Approximately 5% of patients were hospitalized for migraine, with an average of one hospitalization and an average length of stay of 3 days. Approximately 39% of patients had ≥1 blood test, 22% had ≥1 magnetic resonance imaging, 17% had ≥1 electroencephalogram, and 13% had ≥1 computerized tomography scan. Visits to other healthcare providers were common. Limitations: This study is subject to the limitations of chart review studies, such as errors in data entry. Conclusions: Across four European countries, the HRU burden of migraine among patients who previously failed at least two prophylactic treatments was high, indicating a need for more effective prophylactic treatments to appropriately manage migraine and reduce the HRU burden attributable to this common disorder.

Migraine-related healthcare resource use in the emergency department setting: a panel-based chart review in France, Germany, Italy, and Spain.

Objective: Migraine is a common, disabling condition typically characterized by severe headache, nausea, and/or light and sound sensitivity. This study assessed migraine-related health resource utilization (HRU) occurring in the emergency room/accident & emergency department (ER/A&E) setting among European patients with 4 or more migraine days per month. Methods: Patient-level clinical and HRU data were collected via chart extraction by ER/A&E physicians in France, Germany, Italy, and Spain. Eligible patients had 4 or more migraine days in the month prior to a migraine-related ER/A&E visit and a history of migraine, among other criteria. The index date for each patient was defined as the date of an ER/A&E visit for migraine on or after January 1, 2013. Physician and ER/A&E characteristics, patient and disease characteristics, treatment history, migraine-medication used, and migraine-related HRU (i.e. procedures) during the ER/A&E visit were assessed. Descriptive analyses were conducted in the pooled population, and a sensitivity analysis was performed by country. Results: A total of 467 eligible patient's charts (120 in France, 120 in Germany, 107 in Italy, and 120 in Spain) were provided by 136 physicians (36 in France, 36 in Germany, 28 in Italy, and 36 in Spain). On average, patients spent nearly 8 hours in the ER/A&E. Approximately 82% of patients received a blood test, 62% received an electrocardiography, and 46% received a cranial computerized tomography scan. Despite the majority of patients already using acute or prophylactic treatment upon visiting the ER/A&E, almost all patients were administered or prescribed migraine treatment during the visit. Approximately 21% of patients were admitted to the hospital, and over half of patients were referred to a neurologist or headache specialist. Conclusions: European patients who had four or more migraine days in the month prior to a migraine-related ER/A&E visit had high HRU associated with the visit.

A Budget Impact Analysis of the Introduction of Copanlisib for Treatment of Relapsed Follicular Lymphoma in the United States.

BACKGROUND: Copanlisib was recently granted accelerated approval by the FDA for the treatment of adult patients with relapsed follicular lymphoma (FL) after 2 previous systemic therapies. It is important to assess the effect that this and other changes in the treatment landscape of relapsed FL have on a payer's budget to inform formulary decisions. OBJECTIVE: To assess the budget impact associated with the addition of copanlisib to a formulary as third- or higher-line treatment for adult patients with relapsed FL who have received at least 2 previous systemic therapies, from the perspective of a U.S. third-party payer. METHODS: A budget impact model was developed over a 1-year horizon. The model considered a hypothetical population of 1 million people enrolled in a commercial health plan; patients with relapsed FL were identified based on epidemiology data. Treatments included copanlisib and approved and off-label therapies used for management of relapsed FL. Treatment distributions within the target population were based on a market research survey. Drug acquisition, administration, prophylaxis, and monitoring costs were based on prescribing information, clinical trials, literature, and expert opinion. All costs were inflated to 2017 U.S. dollars. Total costs were compared between 2 scenarios, 1 without and 1 with copanlisib on a formulary. A deterministic sensitivity analysis (DSA) was conducted to evaluate the robustness of the model. RESULTS: Within the 1 million-member health care plan, 18 patients had relapsed FL and had received at least 2 previous systemic therapies. Over 1 year, the addition of copanlisib and an increase in the use of obinutuzumab + bendamustine (from 9.0% without copanlisib to 13.1% with copanlisib) and lenalidomide + rituximab (from 0.3% to 12.0%) were estimated to increase drug acquisition costs by $238,536, drug administration and prophylaxis costs by $3,565, and monitoring costs by $539. The increase in total budget was $242,641, corresponding to $0.02 per member per month; 21.8% of this increase was attributable to copanlisib, 12.9% to obinutuzumab + bendamustine, and 65.3% to lenalidomide + rituximab. Results were generally robust in the DSA. CONCLUSIONS: Over a 1-year period, the model found that the addition of copanlisib to a formulary resulted in a small increase in total budget of $242,641, corresponding to $0.02 per patient per month and taking into account a concurrent increase in the use of obinutuzumab + bendamustine and lenalidomide + rituximab. Therefore, adding copanlisib to a formulary appears to be an affordable option for payers. Further studies should be conducted to more comprehensively assess the clinical and economic implications of adding copanlisib to the treatment armamentarium of relapsed FL. DISCLOSURES: This study was funded by Bayer HealthCare Pharmaceuticals. The study sponsor was involved in study design, data interpretation. and data review. All authors contributed to the development of the manuscript and maintained control over the final content. Appukkuttan, Yaldo, Gharibo, and Babajanyan report employment with Bayer HealthCare Pharmaceuticals at the time of this study. Duchesneau, Zichlin, Bhak, and Duh report employment with Analysis Group, which received research funds from Bayer HealthCare Pharmaceuticals for work on this study. A synopsis of the current research was presented in poster format at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial.

BACKGROUND: The randomized phase 3 ELOQUENT-2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab plus lenalidomide and dexamethasone (ELd) versus lenalidomide and dexamethasone (Ld) in relapsed/refractory multiple myeloma (RRMM), and to date, has the longest follow-up of any monoclonal antibody in patients with RRMM. METHODS: In this extended 4-year follow-up of the ELOQUENT-2 trial, the coprimary endpoints of progression-free survival (PFS) and overall response rate as well as the secondary endpoint of overall survival were assessed. In the absence of head-to-head trials comparing Ld-based triplet regimens to guide treatment selection, 4 randomized controlled trials-ELOQUENT-2, ASPIRE, TOURMALINE-MM1, and POLLUX-were indirectly compared to provide insight into the relative efficacy of these regimens in RRMM. RESULTS: Data at 4 years were consistent with 2- and 3-year follow-up data: ELd reduced the risk of disease progression/death by 29% versus Ld (hazard ratio, 0.71) while maintaining safety. The greatest PFS benefit among the assessed subgroups was observed in patients at the median time or further from diagnosis (≥3.5 years) with 1 prior line of therapy, who had a 44% reduction in the risk of progression/death, and in patients in the high-risk category, who had a 36% reduction in favor of ELd. This regimen also showed a relative PFS benefit that was maintained beyond 50 months. CONCLUSIONS: The sustained PFS benefit and long-term safety of ELd at 4 years, similar to those observed at 2 and 3 years, support ELd as a valuable therapeutic option for the long-term treatment of patients with RRMM.

Predictors and Clinical Outcomes of Treatment Intensification in Patients With Type 2 Diabetes Uncontrolled on Basal Insulin in a Real-World Setting.

OBJECTIVE: To understand factors associated with intensification of basal insulin therapy and treatment impact on clinical outcomes in patients with type 2 diabetes (T2D). METHODS: In this retrospective, observational study of the Practice Fusion electronic health record database, eligible patients were adults with T2D, ≥1 basal insulin prescription and office visit in the 6 months before a glycated hemoglobin A1c (A1C) test >7.0% (index date), and no other injectable prescriptions in the 12 months before the index date. Patients were categorized to intensifiers with injectables (rapid-acting insulin [RAI], glucagon-like peptide-1 receptor agonist [GLP-1 RA], or other injectables) or nonintensifiers with injectables (including no change, adding an oral antidiabetes drug, or changing basal insulin dose). Principal outcomes were A1C change, hypoglycemia incidence, and change in body weight. RESULTS: Among 14,653 patients, 2,121 (14.5%) and 12,532 (85.5%) were categorized as intensifiers and nonintensifiers with injectables, respectively. Compared with nonintensifiers, intensifiers were more likely to have an endocrinologist as the prescribing physician (odds ratio [OR], 2.52 [95% confidence interval (CI), 2.16 to 2.94]), hypertension (OR, 1.26 [95% CI, 1.08 to 1.47]), higher baseline A1C (OR, 1.22 [95% CI, 1.17 to 1.26]), obesity (OR, 1.17 [95% CI, 1.01 to 1.36]), and higher body mass index (OR, 1.02 [95% CI, 1.01 to 1.03]). In GLP-1 RA intensifiers, the baseline use of dipeptidyl peptidase-4 inhibitors increased the likelihood of intensification. GLP-1 RA intensifiers had equivalent glycemic control to RAI or other injectables, with a nonsignificantly lower risk of hypoglycemia and reduction in body weight. CONCLUSION: Addition of GLP-1 RA to basal insulin may be an effective strategy for overcoming clinical inertia with injectable therapy in patients with T2D. ABBREVIATIONS: A1C = glycated hemoglobin A1c; BMI = body mass index; CI = confidence interval; DCSI = Diabetes Complications Severity Index; DPP-4 = dipeptidyl peptidase-4; EHR = electronic health record; GLP-1 RA = glucagon-like peptide-1 receptor agonist; ICD-9-CM = International Classification of Diseases-Ninth Revision-Clinical Modification; ICD-10-CM = International Classification of Diseases-Tenth Revision-Clinical Modification; OAD = oral antidiabetes drug; OR = odds ratio; RAI = rapid-acting insulin; SGLT-2 = sodium-glucose cotransporter-2; T2D = type 2 diabetes.

Real-World Economic Outcomes During Time on Treatment Among Patients Who Initiated Sunitinib or Pazopanib as First Targeted Therapy for Advanced Renal Cell Carcinoma: A Retrospective Analysis of Medicare Claims Data.

BACKGROUND: The median age at renal cell carcinoma (RCC) diagnosis is 64 years. However, few studies have assessed the real-world time on treatment (TOT), health resource utilization (HRU), costs, or treatment compliance associated with targeted therapy use among patients in this age group with RCC. OBJECTIVE: To assess the HRU, costs, and compliance during TOT among Medicare patients aged ≥ 65 years with advanced RCC (aRCC) who initiated first targeted therapy with pazopanib or sunitinib. METHODS: Patients with aRCC were identified in the 100% Medicare + Part D databases administered by the Centers for Medicare & Medicaid Services. Eligible patients initiated first targeted therapy with sunitinib or pazopanib (index drug) on or after their first diagnosis of secondary neoplasm between October 19, 2009, and January 1, 2014, and were aged ≥ 65 years as of 1 year before first targeted therapy initiation (index date). Included patients were stratified into pazopanib and sunitinib cohorts based on first targeted therapy and matched 1:1 on baseline characteristics using propensity scores. TOT was defined as the time from the index date to treatment discontinuation (prescription gap > 90 days) or death. Compliance was defined as the ratio of drug supply days to TOT. Monthly all-cause costs and costs associated with RCC diagnosis (medical and pharmacy in 2015 U.S. dollars) and HRU (inpatient [admissions, readmissions, and days], outpatient, and emergency room visits) were assessed in the 1-year post-index period during TOT. Matched cohorts' TOT was compared using Kaplan-Meier analyses and univariable Cox models, and compliance, HRU, and costs were compared using Wilcoxon signed-rank tests. RESULTS: Of 1,711 included patients, 526 initiated pazopanib and 1,185 initiated sunitinib. Before matching, more patients in the pazopanib cohort were white, diagnosed in 2010-2014 versus 2006-2009, and had lung metastases compared with the sunitinib cohort (all P < 0.05). The pazopanib cohort also had higher mean outpatient visits and costs but lower mean total all-cause pharmacy costs, than the sunitinib cohort (all P < 0.05). After matching, the pazopanib and sunitinib cohorts had similar characteristics (mean age 75 years, 58% male, and Charlson Comorbidity Index score of 9.2 in both cohorts) and median TOT (4.8 and 4.1 months, respectively). Among the 522 matched pairs, pazopanib was associated with significantly lower total all-cause health care costs ($8,527 vs. $10,924, respectively [mean difference = $2,397]); total medical costs ($3,991 vs. $5,881, respectively, [$1,890]); and inpatient costs ($2,040 vs. $3,731, respectively, [$1,692]; all P < 0.01) compared with sunitinib. Patients receiving pazopanib had significantly fewer inpatient admissions (0.179 vs. 0.289, respectively) and days (1.063 vs. 1.904, respectively; both P < 0.01) than patients receiving sunitinib. Mean treatment compliance was lower for the pazopanib versus sunitinib cohort (0.91 vs. 0.94, respectively; P < 0.01). CONCLUSIONS: In this retrospective analysis of Medicare patients with aRCC from a TOT perspective, first targeted therapy with pazopanib was associated with significantly lower all-cause health care costs and HRU, but lower compliance, compared with sunitinib. DISCLOSURES: Funding for this research was provided by Novartis Pharmaceuticals. The sponsor was involved in all stages of the study's conduct and reporting. Vogelzang has been a consultant for Novartis, Amgen, Celgene, Medivation, Eisai, Exelixis, and Roche; has spoken at Novartis, Astellas, Johnson and Johnson, Pfizer, Dendreon, Bayer/Algeta, GSK, and Veridex/Janssen; and has received research support from Novartis, Bayer, Exelixis, Progenics, Bavarian Nordic, and Viamet. Pal has been a consultant for Novartis, Pfizer, Aveo, Dendreon, and Myriad and has spoken at Novartis, Pfizer and Medivation. Agarwal has been a consultant or advisor for Novartis, Pfizer, Exelixis, Cerulean Pharma, Medivation, Eisai, and Argos Therapeutics. Swallow, Peeples, Zichlin, and Meiselbach are employees of Analysis Group, which received consultancy fees from Novartis for this project. Li was an employee of Analysis Group during the conduct of this study. Ghate is an employee of Novartis and owns stock/stock options. Perez was an employee of Novartis during the conduct of this study. A synopsis of the economic outcomes was presented at the Academy of Managed Care Pharmacy Nexus 2017 in Denver, Colorado, during March 27-30, 2017. A synopsis of the clinical outcomes was presented at the 22nd ISPOR Annual International Meeting in Boston, Massachusetts, during May 20-24, 2017.