Clinical Outcomes and Treatment Patterns in Adults With FLT3-ITDmut+ Acute Myeloid Leukemia Undergoing Allogeneic Hemopoietic Cell Transplantation in the United States and Canada.

Allogeneic hematopoietic cell transplantation (alloHCT) is used to treat patients with acute myeloid leukemia (AML) with internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITDmut+). However, the effect of different characteristics on outcomes after transplant is not fully understood. The aim of this study was to determine the impact of patient, disease, and transplant characteristics on clinical outcomes and trends in maintenance therapy for patients with FLT3-ITDmut+ AML who underwent their first alloHCT. This was an observational cohort study of adults ≥18 years who were recipients of human leukocyte antigen identical sibling, haploidentical, 8/8 or 7/8 unrelated, or cord blood donor alloHCT in the United States and Canada between 2014 and 2019. Patient, disease, and transplant characteristics were collected from Center for International Blood & Marrow Transplant Research between 2014 and 2022. Patients enrolled in the MORPHO clinical trial (NCT02997202) were excluded. Clinical outcomes were measured from the time of alloHCT by disease status: first complete remission (CR1), second or greater complete remission (≥CR2), or relapsed/refractory (R/R). The primary endpoints of this study were overall survival (OS) and leukemia-free survival (LFS). Key secondary endpoints included relapse after alloHCT, nonrelapse mortality (NRM), time from diagnosis to complete remission, time from complete remission to alloHCT, and maintenance therapy before and after alloHCT. Univariate analyses were conducted with Gray's test and log-rank test, while multivariable analyses were conducted using Cox proportional hazards models. A total of 3147 eligible patients (CR1, n = 2389; ≥CR2, n = 340; R/R, n = 418) were included. Most patient, disease, and transplant characteristics were similar between different disease statuses. In univariate analyses, disease status of CR1 compared with ≥CR2 or R/R was significantly (P < .001) associated with improved OS and LFS, and decreased probability of relapse; NRM likely differed across cohorts after alloHCT (P = .003). In multivariable analyses, patients with a disease status of ≥CR2 and R/R compared with CR1 had significantly shorter OS (hazard ratio [HR] 95% confidence interval [CI], 1.43 [1.19 to 1.72], P = .0001, and 2.14 [1.88 to 2.44], P < .0001, respectively). Patients with a disease status of CR1 at ≤2.6 months had better LFS compared with ≥CR2 and R/R (HR [95% CI], 2.03 [1.56 to 2.63], P < .0001 and 3.98 [3.07 to 5.17], P < .0001, respectively). Patients with a ≥CR2 or R/R disease status at ≤2.6 months had an increased likelihood of relapse compared with CR1 (HR [95% CI], 2.46 [1.82 to 3.33], P < .0001 and 4.68 [3.46 to 6.34], P < .0001, respectively). Disease status was not significantly associated with NRM. We also identified several additional patient, disease, and transplant characteristics that may have been associated with inferior OS and/or LFS and greater relapse and/or NRM. Maintenance therapy usage after alloHCT increased from 2014 to 2019 primarily due to increased FLT3 inhibitor use. In this largest study to date of patients from the United States and Canada with FLT3-ITDmut+ AML, disease status of CR1 at the time of alloHCT was associated with better clinical outcomes. Additional factors were identified that may also impact clinical outcomes, and in total, have the potential to inform clinical decision-making.

Work absenteeism, disability, and lost wages among patients with acute myeloid leukemia and their caregivers: a cohort study using US administrative claims and productivity data.

OBJECTIVE: We describe the impact of acute myeloid leukemia (AML) diagnosis on workplace absenteeism and disability days among patients and their caregivers. METHODS: This retrospective study included adults with newly diagnosed AML (2009-2019) and adult caregivers of patients with newly diagnosed AML, identified from the US Merative™ MarketScan® Commercial Database. The Merative MarketScan Health and Productivity Management Database provided linked patient-level records of workplace absence and short-term (STD) and long-term disability (LTD) data. Endpoints included workplace absence, STD and LTD for patients and caregivers during 12 months pre-AML (baseline) and ≤3 years' follow-up, and corresponding cost of work loss. RESULTS: Patient workplace absence decreased in the months post-AML diagnosis, but the number of STD and LTD leave days claimed increased significantly by sixfold and fourfold, respectively. The proportion of patients making STD leave claims increased within 4-5 months of diagnosis, while the proportion making LTD leave claims increased significantly starting from month 5. Caregiver workplace absence peaked in the first 2 months post-diagnosis and remained elevated versus baseline throughout the study. CONCLUSION: AML diagnosis leads to workplace absenteeism and increased economic burden for patients with AML and their caregivers.

Patient and Physician Preferences for Acute Myeloid Leukemia Maintenance Treatments Following Hematopoietic Stem Cell Transplantation.

Purpose: This study assessed and compared preferences for treatment attributes of maintenance therapies post-hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) and in physicians who treat these patients. Patients and Methods: Patients with AML post HSCT and physicians from the United States, United Kingdom, Canada, and Australia (physicians only) completed a web-based discrete choice experiment (DCE). The DCE used inputs identified via a targeted literature review and qualitative interviews to ascertain relevant treatment attributes and associated levels. Six treatment attributes were selected (chance of 2-year relapse-free survival, quality of life [QoL], risk of serious infections, risk of nausea, chance of achieving transfusion independence, and duration of hospitalization annually), each with three or four levels. The experimental design included 36 choice tasks that presented a pair of hypothetical treatment profiles with varying attribute levels; participants chose a preferred treatment for each choice task. Choice tasks were divided into three blocks of 12 tasks each in the patient survey and 4 blocks of 9 tasks each in the physician survey; survey participants were randomly assigned to one of the blocks. Random parameter logit regression models were used to assess the impact of stated attributes on preferences for maintenance treatment post HSCT. Results: Surveys from 84 patients and 149 physicians were assessed. For patients, QoL was the most important attribute, followed by duration of hospitalization and chance of 2-year relapse-free survival. For physicians, chance of 2-year relapse-free survival was the most important attribute, followed by QoL and risk of serious infections. Conclusion: Differences in how patients and physicians valued post-HSCT maintenance treatment attributes were identified. These differences suggest that patient-centered decision-making may help physicians choose maintenance treatments for patients with AML post HSCT that better meet their treatment needs and improve their treatment satisfaction.

Healthcare resource utilization and costs during first salvage therapy for relapsed or refractory acute myeloid leukemia in the United States.

Real-world US healthcare resource utilization (HRU) and costs during first salvage therapy for relapsed/refractory (R/R) acute myeloid leukemia (AML) are described using IBM MarketScan® data (1/1/2007-6/30/2020). Treatments included high- (HIC) and low-intensity chemotherapy (LIC) alone, and gilteritinib, other FLT3 tyrosine kinase inhibitors (TKIs), and venetoclax with or without chemotherapy. Patients were diagnosed with R/R AML at ≥18 years of age between 1/1/2017-12/31/2019. Patient monthly all-cause HRU and costs were analyzed using a fixed-effects model. Data from 399 patients were analyzed (HIC, n = 104; LIC, n = 133; gilteritinib, n = 14; other FLT3 TKIs, n = 68; venetoclax, n = 80). Inpatient HRU was generally highest with HIC, whereas outpatient HRU was generally highest with LIC and venetoclax. Total all-cause incremental monthly costs appeared to be highest with HIC ($171,982) and similar for LIC ($60,512), gilteritinib ($47,218), other FLT3 TKIs ($43,218), and venetoclax ($77,566). Results highlight HRU and cost differences for R/R AML during first salvage therapy.

The experience of patients with acute myeloid leukemia in remission post-transplant.

The symptoms of acute myeloid leukemia (AML) and its treatment can negatively impact patient functioning and quality of life. Through concept elicitation interviews, we sought to evaluate the experience of patients with AML in remission following hematopoietic stem cell transplant (HSCT). Thirty patients with AML in remission post-HSCT, and eight clinicians with experience treating such patients, were asked to identify symptoms and impacts associated with AML and/or its treatment. The findings were used to develop an AML conceptual disease model to reflect the experience of these patients. We identified five symptoms and six impacts that were salient to patients with AML in remission post-HSCT. Although clinician and patient perspectives largely aligned, emotional and cognitive impacts were most important to patients, whereas clinicians focused on physical impacts. This model could be used to ensure patient-reported outcome measures included in clinical trials are reflective of the post-HSCT AML patient experience.

Patient-reported outcomes from the phase 3 ADMIRAL trial in patients with FLT3-mutated relapsed/refractory AML.

Patient-reported outcomes (PROs) can inform treatment selection and assess treatment value in acute myeloid leukemia (AML). We evaluated PROs from the ADMIRAL trial (NCT02421939) in patients with FLT3-mutated relapsed/refractory (R/R) AML. PRO instruments consisted of Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), Functional Assessment of Chronic Illness Therapy-Dyspnea Short Form (FACIT-Dys SF), EuroQoL 5-Dimension 5-Level (EQ-5D-5L), and leukemia treatment-specific symptom questionnaires. Clinically significant effects on fatigue were observed with gilteritinib during the first two treatment cycles. Shorter survival was associated with clinically significant worsening of BFI, FACT-Leu, FACIT-Dys SF, and EQ-5D-5L measures. Transplantation and transfusion independence in gilteritinib-arm patients were also associated with maintenance or improvement in PROs. Health-related quality of life remained stable in the gilteritinib arm. Hospitalization had a small but significant effect on patient-reported fatigue. Gilteritinib was associated with a favorable effect on fatigue and other PROs in patients with FLT3-mutated R/R AML.

Burden of chemotherapy in patients with relapsed/refractory acute myeloid leukemia in the United States: a retrospective claims database study.

BACKGROUND: Real-world estimates of relapsed or refractory (R/R) acute myeloid leukemia (AML) chemotherapy episode costs are scarce. We quantified chemotherapy episode-related costs and healthcare resource use (HRU) in R/R AML. RESEARCH DESIGN AND METHODS: This real-world, retrospective analysis of United States claims from IQVIA's PharMetrics® Plus database (October 2008-September 2019) identified adults with R/R AML and ≥1 chemotherapy episode. Chemotherapy episode (ie, low- [LIC] or high-intensity [HIC] chemotherapy) costs and HRU were determined using inpatient, outpatient, and pharmacy claims. RESULTS: Mean (SD) and median total all-cause healthcare costs per R/R AML chemotherapy episode were $230,799 ($300,770) and $129,117. Mean (SD) and median adjusted direct R/R AML chemotherapy episode costs were $116,384 ($151,425) and $63,298, with increases noted from the first to the second and subsequent episodes and with HIC. Hospitalizations were the major cost driver; 64.1% of patients had ≥1 hospitalization and 36% required an intensive care unit stay. CONCLUSIONS: R/R AML chemotherapy episode costs were high, with higher costs reported with HIC and increasing lines of chemotherapy. Hospitalizations were a main cost driver. Novel therapies with comparable or improved effectiveness and decreased need for hospitalizations versus chemotherapy may help alleviate the clinical and economic burden of R/R AML.

Cost-effectiveness of gilteritinib for relapsed/refractory FLT3mut+ acute myeloid leukemia.

BACKGROUND: Patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) and confirmed feline McDonough sarcoma (FMS)-like tyrosine kinase 3 gene mutations (FLT3mut+) have a poor prognosis and limited effective treatment options. Gilteritinib is the first targeted therapy approved in the United States and Europe for R/R FLT3mut+ AML with significantly improved efficacy compared with existing treatments. OBJECTIVE: To evaluate gilteritinib against salvage chemotherapy (SC) and best supportive care (BSC) over a lifetime horizon among adult patients with R/R FLT3mut+ AML from a US third-party payer's perspective. METHODS: The model structure of this cost-effectiveness analysis included a decision tree to stratify patients based on their hematopoietic stem cell transplantation (HSCT) status, followed by 2 separate 3-state partitioned survival models to predict the long-term health status conditional on HSCT status. The ADMIRAL trial data and literature were used to predict probabilities of patients being in different health states until a conservative cure point at year 3. Afterwards, living patients followed the survival outcomes of long-term survivors with AML. Model inputs for utilities, medical resource use, and costs were based on the ADMIRAL trial, published literature, and public sources. All costs were inflated to 2019 US dollars (USD). Total incremental costs (in 2019 USD), life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic sensitivity analyses and probabilistic sensitivity analyses were performed. RESULTS: Over a lifetime horizon with a 3.0% annual discount rate, the base-case model estimated that gilteritinib led to an increase of 1.29 discounted QALYs at an additional cost of $148,106 vs SC, corresponding to an ICER of $115,192 per QALY; for BSC, results were an increase of 2.32 discounted QALYs, $249,674, and $107,435, respectively. The base-case findings were robust in sensitivity analyses. The estimated probabilities of gilteritinib being cost-effective vs SC and BSC were 90.5% and 99.8%, respectively, in the probabilistic sensitivity analyses, based on a willingness-to-pay threshold of $150,000 per QALY. CONCLUSIONS: Gilteritinib is a cost-effective novel treatment for patients with R/R FLT3mut+ AML in the United States. DISCLOSURES: This work was supported by Astellas Pharma, Inc., which was involved in all stages of the research and manuscript development. Garnham, Pandya, and Shah are employees of Astellas and hold stock/stock options. Zeidan consulted and received personal fees/honoraria and research funding from Astellas. Zeidan also has received research funding from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff Oncology, Incyte, Takeda, Novartis, Amgen, Aprea, and ADC Therapeutics; has participated in advisory boards; has consulted with and/or received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Daiichi Sankyo, Taiho, Seattle Genetics, BeyondSpring, Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Syndax, Gilead, Kura, Aprea, Lox Oncology, Genentech, Servier, Jasper, Tyme, and Epizyme; has served on clinical trial committees for Novartis, Abbvie, Geron, Gilead, Kura, Lox Oncology, BioCryst, and Celgene/BMS; and has received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology. Qi and Yang are employees of Analysis Group, Inc., which received consulting fees from Astellas for work on this study. Part of this material was presented at the American Society of Hematology (ASH) Annual Meeting; December 7-10, 2019; Orlando, FL.

A budget impact analysis of gilteritinib for the treatment of relapsed or refractory FLT3 mut+ acute myeloid leukemia in a US health plan.

AIMS: To estimate the economic impact of the introduction of gilteritinib for the treatment of relapsed/refractory (R/R) FLT3 mutation-positive (FLT3 mut+) acute myeloid leukemia (AML) from a US payer's perspective. METHODS: A budget impact model (BIM) was developed to evaluate the 3-year total budgetary impact of treating adults with R/R FLT3 mut+ AML eligible for gilteritinib in a hypothetical US health plan. Total costs (drugs/administration, hospitalization, monitoring, adverse events, transfusions, subsequent hematopoietic stem cell transplantation, post-progression, and FLT3 testing) were estimated before and after gilteritinib entry. The budget impact was the total cost difference between the two scenarios. The target population size and cost inputs were based on public data or published literature, drug market share was informed by market research data, and the model included recommended treatments for R/R FLT3 mut+ AML per clinical guidelines. Deterministic sensitivity analyses (DSAs) and scenario analyses varying key model inputs and assumptions were conducted to test for robustness. RESULTS: In a hypothetical health plan with 1 million members, 20.9 adults with R/R FLT3 mut+ AML were estimated to be eligible for gilteritinib. Of these, it was assumed 30.0% would be treated with gilteritinib in Year 1 following gilteritinib entry, increasing the total plan budget by $663,795 and the per-member-per-month (PMPM) cost by $0.055. In Years 2-3, the market share of gilteritinib increased to 45.0%, increasing the total plan budget impact by $1,078,371 and $1,087,230, and the PMPM cost by $0.090 and $0.091, respectively. The model results remained robust in DSAs and scenario analyses, with the largest impact observed when the projected uptake of gilteritinib was changed. LIMITATIONS: The results of this BIM are contingent upon the model's assumptions and inputs. CONCLUSIONS: Adding gilteritinib to the formulary for the treatment of adults with R/R FLT3 mut+ AML had a minimal budget impact from a US payer's perspective.

Economic and Clinical Burden of Acute Myeloid Leukemia Episodes of Care in the United States: A Retrospective Analysis of a Commercial Payer Database.

BACKGROUND: In the United States, the incidence of acute myeloid leukemia (AML) has steadily increased over the last decade; in 2019, it was estimated that AML would affect 21,450 new patients and lead to 10,920 deaths. Detailed real-world cost estimates and comparisons of key AML treatment episodes, such as in high-intensity chemotherapy (HIC), low-intensity chemotherapy (LIC), hematopoietic stem cell transplantation (HSCT), and relapsed/refractory (R/R), are scarce in the commercially insured U.S. OBJECTIVE: To examine health resource utilization (HRU), clinical burden, and direct health care costs across various AML treatment episodes in a large sample of commercially insured U.S. METHODS: A retrospective cohort analysis was conducted. Patients with newly diagnosed AML were followed to identify the key active treatment episodes across the course of their disease. Data were obtained from 2 sources: IQVIA's Real-World Data (RWD) Adjudicated Claims Database - U.S. (formerly known as PharMetrics Plus), which comprises adjudicated claims for more than 150 million unique enrollees across the United States, and IQVIA Charge Detail Master Hospital Database, which has detailed data regarding services received in an inpatient setting. Calculation of all-cause HRU was based on physician office visits, nonphysician office visits, emergency department visits, inpatient visits, and outpatient pharmacy utilization. Calculation of all-cause health care costs was based on total allowed costs and reported by the following cost components: physician office visits, nonphysician office visits, emergency department visits, inpatient visits, and outpatient pharmacy utilization. Symptom and toxicity events were estimated via proxies such as diagnosis codes, procedures, and treatments administered. RESULTS: The final study sample consisted of 1,542 HIC-induction (HIC-I), 591 HIC-consolidation (HIC-C), 628 LIC, 1,000 patients with HSCT, and 707 patients with R/R AML. Total mean episode costs were highest in R/R episodes ($439,104), followed by HSCT ($329,621), HIC-I ($198,657), HIC-C ($73,428), and LIC ($53,081) episodes. Across all treatment episodes, hospitalization was the largest contributor to cost with mean hospitalization costs ranging from $308,978 in the R/R setting to $49,580 for patients receiving LIC; of these, costs related to intensive care unit admission were a noteworthy contributor. In patients with R/R AML and HSCT, expenditures related to pharmacy utilization averaged $24,640 and $12,203, respectively, and expenditures related to physician office visits averaged $10,926 and $6,090, respectively; these expenditures were much lower across other episodes. Across all categories of symptom and toxicity events, cardiovascular events was the only category of event that was a significant predictor of higher cost across all episodes. Symptom and toxicity events commonly associated with AML were associated with significantly increased costs, especially in R/R episodes. CONCLUSIONS: This resource utilization and direct health care cost analysis highlights the substantial economic burden associated with key AML treatment episodes in the United States, specifically during HIC-I, HSCT, and R/R episodes. DISCLOSURES: This study was funded by Astellas Pharma. Astellas employees were involved in the study design, interpretation of data, writing of the manuscript, and the decision to submit the manuscript for publication. Pandya and Wilson are employees of Astellas Pharma U.S. Walsh was an employee of Astellas Pharma U.S. while the study was conducted. Chen, McGuiness, and Wade are employees of IQVIA, which received funding from Astellas Pharma U.S. Madeiros was employed at Stanford University while this study was conducted and received a consulting fee from Astellas for work on this study. Data discussed in this study were previously presented at the 59th Annual American Society for Hematology Meeting & Exposition, 2017; December 9-12, 2017; Atlanta, GA.

Economic and Clinical Burden of Relapsed and/or Refractory Active Treatment Episodes in Patients with Acute Myeloid Leukemia (AML) in the USA: A Retrospective Analysis of a Commercial Payer Database.

This retrospective study estimated healthcare resource use (HRU), symptoms and toxicities (SxTox), and costs in relapsed/refractory (R/R) patients with acute myeloid leukemia (AML), stratified by hematopoietic stem cell transplantation (HSCT) status. Claims data were used to identify adult patients with AML diagnoses from 1 January 2008 to 31 March 2016 in the USA. Patients were considered R/R if they had an AML relapse ICD-9 code (205.02) or a line of therapy consistent with R/R disease. The final R/R sample (N = 707) included 476 patients with and 231 patients without HSCT. The mean total episode cost (from relapse date to death or end of study period) for all patients was $439,104 (with HSCT $524,595 and without HSCT $263,310). Inpatient visits accounted for the greatest cost component (mean $308,978) followed by intensive care unit stays (mean $221,537), non-clinician (e.g., lab tests) visits (mean $30,909), and outpatient pharmacy utilization (mean $24,640). Patients with HSCT appeared to have longer episodes of care compared with patients without HSCT (16.8 vs 11.1 months), perhaps reflecting longer survival for HSCT patients. Mean number of visits within each category and their associated costs appeared to be higher in patients with HSCT compared with patients without HSCT. Patients with HSCT appeared to experience more SxTox compared with patients without HSCT across all categories. Results of the current study suggest that there is a substantial HRU and cost burden on R/R AML patients in the USA receiving active treatments. More effective therapies with improved tolerability would meet this tremendous unmet need in the R/R AML population.Funding: Astellas Pharma, Inc.

Treatment patterns in patients with acute myeloid leukemia in the United States: a cross-sectional, real-world survey.

OBJECTIVE: The aim of this analysis was to examine treatment patterns in patients with acute myeloid leukemia (AML) in routine clinical practice in the United States, including factors influencing the choice of front-line treatment intensity and the effect of age and treatment line. METHODS: We used data from the Adelphi AML Disease Specific Programme, a real-world, cross-sectional survey conducted in 2015. Physicians completed patient record forms providing patients' demographic and clinical characteristics. RESULTS: In total, 61 academic, non-academic, and office-based hematologists and hematology/oncology specialists provided data on 457 patients with AML; 284 had ≥20% blasts (World Health Organization defined AML) and were included in the analysis. In the front-line setting, 60% of patients received high-intensity therapy, most commonly cytarabine plus anthracycline; the most common low-intensity treatments were hypomethylating agents. Primary drivers for selecting high-intensity versus low-intensity treatment were age, performance status and comorbidities; 67%, 64% and 61% of physicians stated they would prescribe high-intensity treatment to patients aged <65 years, with good performance status or no comorbidities, respectively. In practice, patients aged <60 years were more likely to receive high-intensity induction treatment (high vs. low intensity by age p < .0001). In a selected cohort of relapsed/refractory patients, 69% of patients received high-intensity therapy (78% of patients aged <60 years and 57% of patients aged ≥60 years). CONCLUSIONS: Most patients in this analysis of real-world survey data received well established, front-line induction therapies. Treatment intensity was determined by age, comorbidities and performance status, as recommended by guidelines.

Real-World Impact of Physician and Patient Discordance on Health-Related Quality of Life in US Patients with Acute Myeloid Leukemia.

INTRODUCTION: There is limited understanding concerning the health-related quality of life (HRQoL) in acute myeloid leukemia (AML) patients. Due to an overlap of symptoms, it can be difficult to separate disease versus treatment-related effects. Study objectives were to understand the impact of factors that might influence patients' HRQoL, assess the degree of concordance in symptom reporting by patients and physicians, and assess the impact of any discordance on HRQoL in AML patients. METHODS: Physicians in the USA captured demographics, current AML treatment and symptoms for 82 AML patients who completed the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu), 5-Dimension EuroQol Questionnaire (EQ-5D-3L) and Cancer Treatment Satisfaction Questionnaire (CTSQ). Effect size (ES) and clinically meaningful differences between AML subgroups were assessed, as was the impact of disagreement between patients and physicians regarding symptom recognition. RESULTS: Clinically meaningful lower overall FACT-Leu scores were observed for: relapsed/refractory versus non-relapsed/refractory AML patients (92.5 vs. 103.7; P = 0.09; ES = 0.439), hypomethylating agent (HMA) monotherapy versus other therapies in patients with low treatment intensity (89.9 vs. 112.9; P = 0.0021; ES = 0.971) and presence/absence of FLT3-ITD mutation (85.5 vs. 100; P = 0.148; ES = 0.816). Differences in health state were also clinically meaningful between patients with/without FLT3-ITD; EQ-5D-Visual Analog Scale (VAS) (47.6 vs. 63.7; P = 0.0428; ES = 0.816). Patients were more likely than physicians to report bruising (κ = 0.1292), fatigue (κ = 0.0836), bleeding (κ = 0.0177), weight loss (κ = 0.0821) and appetite loss (κ = - 0.0246). FACT-Leu was associated with patient-physician discordance on bleeding (difference - 14.12; P = 0.046), weight loss (- 21.22; P = 0.001) and appetite loss (- 12.58; P = 0.027). CONCLUSIONS: HRQoL is generally low for AML patients, especially for particular subgroups. Discordance in symptom reporting between patients and physicians was common and associated with further negative impacts on HRQoL. There may be many reasons for this but better communication between physicians and patients may lead to shared objectives and improvement in patients' HRQoL. FUNDING: Astellas Pharma, Inc.

Number needed to treat and associated incremental costs of treatment with enzalutamide versus abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: Enzalutamide (ENZA) and abiraterone acetate plus prednisone (AA) are approved second-generation hormone therapies for chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). This study compared ENZA with AA in chemotherapy-naïve mCRPC by calculating the number needed to treat (NNT) and associated incremental costs to achieve one additional chemotherapy-naïve patient with mCRPC free of radiographic progression, chemotherapy, or death over a 1-year time horizon. METHODS: Clinical outcomes were obtained from the PREVAIL and COU-AA-302 trials. Three outcomes were evaluated: radiographic progression-free survival, time to cytotoxic chemotherapy initiation, and overall survival at 1 year. NNT was calculated as the reciprocal of the outcome event rate difference for ENZA compared with AA. The incremental costs to achieve one additional outcome at 1 year were calculated as the difference in cost per treated patient multiplied by the NNT. Per-treated-patient costs were considered from a US payer perspective and included medications, monitoring, adverse events, post-progression treatments, and end-of-life care. RESULTS: Within a 1-year time horizon, the total cost per treated patient for ENZA was $2,666 less than AA. Compared with AA, treating 14 patients with ENZA resulted in one additional patient free of progression or death over 1 year; treating 26 patients with ENZA resulted in one additional patient with chemotherapy delayed over 1 year; and treating 91 patients with ENZA resulted in one additional patient free of death over 1 year. Therefore, ENZA is cost-effective compared with AA for all three outcomes evaluated, and the modeled results suggest ENZA is associated with potentially improved clinical outcomes in delaying chemotherapy initiation and disease progression for chemotherapy-naïve patients. The results are robust in sensitivity analyses, where the effect of changes in key model inputs and assumptions were tested. CONCLUSION: The results modeled in the present study suggest ENZA is cost-effective compared with AA for treating chemotherapy-naïve patients with mCRPC.

Hyperuricemia in young adults and risk of insulin resistance, prediabetes, and diabetes: a 15-year follow-up study.

The objective of this study was to assess the utility of hyperuricemia as a marker for diabetes and prediabetes (impaired fasting glucose) and insulin resistance in young adults. Using Cox proportional hazards regression models, the authors analyzed 15-year follow-up data on 5,012 persons in 4 US cities who were aged 18-30 years and diabetes-free at the time of enrollment. At baseline (1986), 88% of participants had a body mass index (weight (kg)/height (m)(2)) less than 30. During the follow-up period (through 2001), the incidence rates of diabetes and prediabetes (insulin resistance and impaired fasting glucose) were higher among persons with greater serum urate concentrations. In multivariable Cox regression analyses that adjusted for age, gender, race, body mass index, family history of diabetes, diastolic blood pressure, total cholesterol, smoking, and alcohol use, the hazard ratios for diabetes, insulin resistance, and prediabetes among persons with hyperuricemia (serum urate level >7 mg/dL vs. ≤7.0 mg/dL) were 1.87 (95% confidence interval (CI): 1.33, 2.62), 1.36 (95% CI: 1.23, 1.51), and 1.25 (95% CI: 1.04, 1.52), respectively. This observation was generally consistent across subgroups. The authors conclude that hyperuricemia in the midtwenties is an independent marker for predicting diabetes and prediabetes among young adults in the subsequent 15 years.

Chronic kidney disease in gout in a managed care setting.

BACKGROUND: To study the prevalence of chronic kidney disease (CKD) and its impact on allopurinol dosing and uric acid control among patients with gout. METHODS: This was a retrospective study using data from a large US health plan. Claims and laboratory data were analyzed for enrollees from the health plan database from January 2002 through December 2005. Patients with gout were identified from pharmacy and medical claims data based on the presence of codes for gout medication or gout diagnosis. Severity of CKD was determined using the estimated glomerular filtration rate (eGFR). Allopurinol titration was defined as a change in average daily dose from first prescription to last prescription of ≥ 50 mg. RESULTS: A total of 3,929 patients were identified for inclusion in this study, 39% of whom had CKD (based on having an eGFR < 90 mL/min/1.73 m2). Subjects with CKD were older (p < 0.01) and more likely to be women (p < 0.01), had a greater number of comorbid conditions (p < 0.01), and were more likely to be prescribed allopurinol (p < 0.01) compared to those with no CKD. The average starting dose of allopurinol was lower among those with CKD, and it decreased with worsening kidney function. Among the 3,122 gout patients who used allopurinol, only 25.6% without CKD and 22.2% with CKD achieved a serum uric acid concentration of < 6.0 mg/dL (p = 0.0409). Also, only 15% of allopurinol users had an upward dose titration (by ≥50 mg), but the average increase in dose did not differ significantly between those with and without CKD. CONCLUSIONS: About two out of every five patients with gout in this population had CKD. Allopurinol doses were not adjusted in the majority of CKD patients. Serum uric acid control in gout was poor among patients without CKD and even worse among those with CKD.

Hyperuricemia and the risk for subclinical coronary atherosclerosis--data from a prospective observational cohort study.

INTRODUCTION: Our purpose was to test the hypothesis that hyperuricemia is associated with coronary artery calcification (CAC) among a relatively healthy population, and that the extent of calcification is directly proportional to the serum uric acid (sUA) concentration. METHODS: Data from 2,498 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were analyzed using logistic regression models. Subjects were free of clinical heart disease, diabetes, and renal impairment. The main measure was the presence of any CAC by computerized tomography (Agatston score >0). RESULTS: Forty-eight percent of the study participants were male and 45% were African-American. Mean (± SD) age was 40 ± 4 years, body mass index 28 ± 6 kg/m2, Framingham risk score -0.7 ± 5%, blood pressure 113 ± 14/75 ± 11 mmHg, alcohol consumption 12 ± 27 ml/day, and sUA 297 ± 89 µmol/L (5.0 ± 1.5 mg/dL). Prevalence of CAC increased with sUA concentration among both men and women. Adjusted for age, gender, race, lipoproteins, triglycerides, smoking, blood pressure, presence of metabolic syndrome, C-reactive protein, waist circumference, alcohol use, creatinine, and serum albumin, the highest quartile of sUA (>393 µmol/L [6.6 mg/dL] for men and >274 µmol/L [4.6 mg/dL] for women) was associated with an odds ratio of 1.87 (1.19-2.93) compared to the lowest quartile (<291 µmol/L [4.9 mg/dL] for men and <196 µmol/L [3.3 mg/dL] for women). Among those with any CAC, each unit increase in sUA was associated with a 22% increase in Agatston score (P = 0.008) after adjusting for the above covariates. CONCLUSIONS: Hyperuricemia is an independent risk factor for subclinical atherosclerosis in young adults.

Relationship between physician specialty and allopurinol prescribing patterns: a study of patients with gout in managed care settings.

OBJECTIVE: Allopurinol is used to lower serum uric acid (sUA) levels in gout patients. The objective of this study was to investigate the influence of physician specialty on allopurinol treatment patterns and sUA control. DESIGN AND METHODS: This was a retrospective study using claims from a managed care database of US health plan enrollees. Gout patients at least 18 years of age who received allopurinol were identified from the database between January 1, 2002 and April 30, 2007. The index date was defined as the date of the earliest allopurinol claim, and patients were required to have health plan enrollment for at least 365 days prior to and following the index date for inclusion. Physician specialty was determined using the index allopurinol claim. Dosage of allopurinol prescription(s) and number of gout flares were determined from claims data. sUA measurements were used to assess goal attainment over a period of at least one year following the index allopurinol prescription. RESULTS: There were 3363 patients with gout of whom 69.9% received an index allopurinol prescription from a generalist/internist, 5.7% from a rheumatologist, 2.6% from a nephrologist, and 21.8% from a physician with other specialty. Of patients receiving their index prescription from a nephrologist, 38.7% reached the sUA goal of <6 mg/dL (357 µmol/L), as compared to patients prescribed by a rheumatologist, generalist/internist, or other physician (35.4%, 31.4%, and 39.4%, respectively; P = 0.015). When controlling for patient characteristics, multivariate analysis did not reveal statistically significant different odds of sUA goal attainment based on prescribing physician specialty, though separate analyses indicated that patients prescribed by a nephrologist had fewer gout flares. Change in allopurinol dosage from initial to final dose was more frequent among patients prescribed by rheumatologists and nephrologists. CONCLUSION: There is significant heterogeneity in the specialists' management of sUA levels in patients with gout, possibly reflecting differences in case mix and treatment approaches. Limitations related to the use of claims data, such as inability to observe medications filled over-the-counter, should be considered when interpreting study results.