Trends in overall mortality among US veterans with primary myelofibrosis.

BACKGROUND: Primary myelofibrosis [PMF] is a myeloproliferative neoplasm associated with reduced overall survival (OS). Management strategies for PMF have evolved over the last two decades, including approval of ruxolitinib as the first Janus kinase 1 (JAK1)/JAK2 inhibitor for patients with intermediate or high-risk myelofibrosis. This study assessed changes in mortality before and after ruxolitinib approval, independent of ruxolitinib treatment. METHODS: This retrospective study investigated mortality trends among US veterans with PMF in 2 time periods, pre-ruxolitinib approval (01/01/2007-12/31/2010) and post-ruxolitinib approval (01/01/2015-09/30/2018). Deidentified patient-level data were extracted from US Veterans Health Administration (VHA) databases using PMF diagnosis codes; index was the first PMF diagnosis date. The analysis included adults with ≥2 PMF claims during the analysis periods who were continuously enrolled in the VHA plan 1 calendar year prior to and 6 months post-index and had ≥1 available International Prognostic Scoring System (IPSS) risk factor (available factors were age > 65, hemoglobin < 10 g/dL, and white blood cell count > 25 × 109/L; each counted as one point). Patients with ≥1 MF diagnosis for 12 months before the index period were excluded. Ruxolitinib treatment was not a requirement to be included in the post-ruxolitinib approval cohort. Mortality rates and OS were estimated using the Kaplan-Meier approach; all-cause mortality hazard ratio was estimated using univariate Cox regression. RESULTS: The pre- and post-ruxolitinib approval cohorts included 193 and 974 patients, respectively, of which 80 and 197 had ≥2 IPSS risk factors. Ruxolitinib use in the post-ruxolitinib cohort was 8.5% (83/974). At end of follow-up, median (95% CI) OS was significantly shorter in the pre-ruxolitinib cohort (1.7 [1.2-2.6] years vs not reached [3.4-not reached]; P < 0.001). Overall mortality rates for the pre- versus post-ruxolitinib approval cohorts were 79.8% versus 47.3%, respectively, and overall risk of death was 53% lower in the post-ruxolitinib period (hazard ratio, 0.47; 95% CI, 0.37-0.58; P < 0.001). Mortality rates were lower among patients with < 2 vs ≥2 IPSS risk factors. CONCLUSIONS: Although veterans with PMF have high overall mortality rates, and results in this population might not be generalizable to the overall population, there was a significant lowering of mortality rate in the post-ruxolitinib period.

Temporal Changes in Cholangiocarcinoma Incidence and Mortality in the United States from 2001 to 2017.

BACKGROUND: Previous studies report increasing cholangiocarcinoma (CCA) incidence up to 2015. This contemporary retrospective analysis of CCA incidence and mortality in the US from 2001-2017 assessed whether CCA incidence continued to increase beyond 2015. PATIENTS AND METHODS: Patients (≥18 years) with CCA were identified in the National Cancer Institute Surveillance, Epidemiology, and End Results 18 cancer registry (International Classification of Disease for Oncology [ICD-O]-3 codes: intrahepatic [iCCA], C221; extrahepatic [eCCA], C240, C241, C249). Cancer of unknown primary (CUP) cases were identified (ICD-O-3: C809; 8140/2, 8140/3, 8141/3, 8143/3, 8147/3) because of potential misclassification as iCCA. RESULTS: Forty-thousand-and-thirty CCA cases (iCCA, n=13,174; eCCA, n=26,821; iCCA and eCCA, n=35) and 32,980 CUP cases were analyzed. From 2001-2017, CCA, iCCA, and eCCA incidence (per 100 000 person-years) increased 43.8% (3.08 to 4.43), 148.8% (0.80 to 1.99), and 7.5% (2.28 to 2.45), respectively. In contrast, CUP incidence decreased 54.4% (4.65 to 2.12). CCA incidence increased with age, with greatest increase among younger patients (18-44 years, 81.0%). Median overall survival from diagnosis was 8, 6, 9, and 2 months for CCA, iCCA, eCCA, and CUP. From 2001-2016, annual mortality rate declined for iCCA (57.1% to 41.2%) and generally remained stable for eCCA (40.9% to 37.0%) and for CUP (64.3% to 68.6%). CONCLUSIONS: CCA incidence continued to increase from 2001-2017, with greater increase in iCCA versus eCCA, whereas CUP incidence decreased. The divergent CUP versus iCCA incidence trends, with overall greater absolute change in iCCA incidence, provide evidence for a true increase in iCCA incidence that may not be wholly attributable to CUP reclassification.

Real-world survival of US patients with intermediate- to high-risk myelofibrosis: impact of ruxolitinib approval.

The Janus kinase inhibitor ruxolitinib is approved for the treatment of myelofibrosis (MF) and improved overall survival (OS) versus control therapy in the phase 3 COMFORT trials. The aim of this retrospective analysis was to examine the real-world impact of ruxolitinib on OS in patients with MF. The US Medicare Fee-for-Service claims database (parts A/B/D) was used to identify patients with ≥ 1 inpatient or ≥ 2 outpatient claims with an MF diagnosis (January 2010-December 2017). Eligible patients with MF were ≥ 65 years old (intermediate-1 or higher risk based on age). Patients were divided into 3 groups based on ruxolitinib approval status at diagnosis and ruxolitinib exposure: (1) preapproval, ruxolitinib-unexposed; (2) post-approval, ruxolitinib-unexposed; and (3) post-approval, ruxolitinib-exposed. In total, 1677 patients with MF were included (preapproval [all ruxolitinib-unexposed], n = 278; post-approval, n = 1399 [ruxolitinib-unexposed, n = 1127; ruxolitinib-exposed, n = 272]). Overall, median age was 78 years, and 39.8% were male. Among patients with valid death dates (preapproval, n = 119 [42.8%]; post-approval, ruxolitinib-unexposed, n = 382 [33.9%]; post-approval ruxolitinib-exposed, n = 54 [19.9%]), 1-year survival rates were 55.6%, 72.5%, and 82.3%, and median OS was 13.2 months, 44.4 months, and not reached, respectively. Risk of mortality was significantly lower post- versus preapproval regardless of exposure to ruxolitinib (ruxolitinib-unexposed: adjusted hazard ratio [HR], 0.67; ruxolitinib-exposed: adjusted HR, 0.36; P < 0.001 for both); post-approval, mortality risk was significantly lower in ruxolitinib-exposed versus ruxolitinib-unexposed patients (adjusted HR, 0.61; P = 0.002). Findings from this study complement clinical data of ruxolitinib in MF by demonstrating a survival benefit in a real-world setting.

Inpatient Healthcare Resource Utilization, Costs, and Mortality in Adult Patients with Acute Graft-versus-Host Disease, Including Steroid-Refractory or High-Risk Disease, following Allogeneic Hematopoietic Cell Transplantation.

Acute graft-versus-host disease (GVHD) contributes to poor outcomes following allogeneic hematopoietic cell transplantation (HCT). Data are limited regarding the economic burden of acute GVHD, particularly steroid-refractory or high-risk (SR/HR) disease. This retrospective analysis of the Premier Healthcare Database reports inpatient healthcare resource utilization (HCRU), costs, and mortality during initial hospitalization for allogeneic HCT and through 100 days post-HCT among patients who developed acute GVHD, including a subgroup with SR/HR disease, compared with patients without GVHD. The analysis included adults discharged for first HCT between January 1, 2011, and June 30, 2016 (acute GVHD, n = 906; SR/HR acute GVHD, n = 158; no GVHD, n = 1529). During the initial hospitalization for HCT, patients with acute GVHD and SR/HR acute GVHD (n = 455 and 125, respectively) had significantly longer median lengths of stay (31 and 46 days versus 24 days) and higher median total costs ($153,849 and $205,880 versus $97,417) versus patients with no GVHD (n = 1529; P < .0001 for all). During the 100-day post-HCT period, patients with acute GVHD and SR/HR acute GVHD had higher readmission rates (78.3% and 77.2% versus 28.3%; P < .0001) and inpatient mortality rates (20.2% and 35.4% versus 8.9%; P < .0001) versus patients with no GVHD. In summary, acute GVHD, especially SR/HR disease, is associated with longer inpatient stays, higher readmission rates, and higher inpatient mortality compared with no GVHD.

Healthcare resource utilization and costs associated with acute graft-versus-host disease following allogeneic hematopoietic cell transplantation.

PURPOSE: The contribution of acute graft-versus-host disease (GVHD) to healthcare resource utilization (HCRU) and costs following allogeneic hematopoietic cell transplantation (HCT) has not been extensively investigated. The objective of this study was to estimate both inpatient and outpatient HCRU and costs associated with acute GVHD during the 100-day and 1-year periods after allogeneic HCT in the USA. METHODS: A retrospective analysis of administrative claims from the Optum® Research Database of patients aged ≥ 12 years who received HCT between 2010 and 2016 was conducted. Costs and HCRU among patients with acute GVHD and no GVHD were compared during the 100-day (acute GVHD, n = 723; no GVHD, n = 385) and 360-day (acute GVHD, n = 445; no GVHD, n = 227) periods after HCT. RESULTS: Patients with acute GVHD had significantly more (P < 0.001) mean office visits (47 vs 32), hospital outpatient visits (71 vs 35), and inpatient stays (2.8 vs 1.1) than patients with no GVHD during 360 days post-HCT; similar findings were observed over the 100-day period. Mean total all-cause costs were significantly higher (P < 0.001) for patients with acute GVHD versus no GVHD during both post-HCT periods (100-day, $316,458 vs $215,229; 360-day, $466,720 vs $263,568). Additional factors associated with increased 360-day costs included young age (12-17 years; P < 0.001) and peripheral blood as graft source (P = 0.03). CONCLUSION: Acute GVHD was associated with significant HCRU and costs in the first 100 days of transplant, increasing over the first year post-HCT. Inpatient care was the primary driver, but outpatient care and related costs were also increased.

Relationship between symptom burden and disability leave among patients with myeloproliferative neoplasms (MPNs): findings from the Living with MPN patient survey.

Patients with myeloproliferative neoplasms (MPNs) experience burdensome symptoms that negatively affect their quality of life. How MPN symptoms relate with medical disability leave (MDL) among patients with the disease has not been previously examined. Using data collected from the Living with MPNs patient survey, symptom burden and functional status were compared in patients who reported taking MDL due to their MPN versus patients who reported no changes in employment status. Among 592 patients who were employed full- or part-time at diagnosis, 24.8% reported taking ≥ 1 MDL and 49.4% reported no change in employment status as a result of their MPN. Of the patients who took MDL, 29.9% took ≥ 2 MDLs, and most patients (62.6%) did not return to work. All 10 symptoms comprising the MPN Symptom Assessment Form were significantly more frequent and severe in patients who took MDL compared with those who had no employment change. Furthermore, functional impairments were also significantly more frequent among patients who went on MDL versus those with no employment change. Effective management of MPN-related symptoms may reduce disability leave among patients with high symptom burden.

Hematocrit levels and thrombotic events in patients with polycythemia vera: an analysis of Veterans Health Administration data.

Patients with polycythemia vera (PV) have a high incidence of thrombotic events (TEs), contributing to a greater mortality risk than the general population. The relationship between hematocrit (HCT) levels and TE occurrence among patients with PV from the Veterans Health Administration (VHA) was evaluated to replicate findings of the CYTO-PV trial with a real-world patient population. This retrospective study used VHA medical record and claims data from the first claim with a PV diagnosis (index) until death, disenrollment, or end of study, collected between October 1, 2005, and September 30, 2012. Patients were aged ≥ 18 years at index, had ≥ 2 claims for PV (ICD-9-CM code, 238.4) ≥ 30 days apart during the identification period, continuous health plan enrollment from 12 months pre-index until end of study, and ≥ 3 HCT measurements per year during follow-up. This analysis focused on patients with no pre-index TE, and with all HCT values either < 45% or ≥ 45% during the follow-up period. The difference in TE risk between HCT groups was assessed using unadjusted Cox regression models based on time to first TE. Patients (N = 213) were mean (SD) age 68.9 (11.5) years, 98.6% male, and 61.5% white. TE rates for patients with HCT values < 45% versus ≥ 45% were 40.3% and 54.2%, respectively. Among patients with ≥ 1 HCT before TE, TE risk hazard ratio was 1.61 (95% CI, 1.03-2.51; P = 0.036). This analysis of the VHA population further supports effective monitoring and control of HCT levels < 45% to reduce TE risk in patients with PV.

Impact of Myeloproliferative neoplasms on patients' employment status and work productivity in the United States: results from the living with MPNs survey.

BACKGROUND: Patients with the myeloproliferative neoplasms (MPNs) myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are at increased risk for thrombotic and cardiovascular events and experience a variety of burdensome symptoms. However, there is a paucity of data in the biomedical literature about how MPNs impact productivity in the workplace. This analysis of the Living with MPNs survey was conducted to evaluate the impact of MPNs on employment, career potential, and work productivity. METHODS: This cross-sectional online survey included respondents aged 18-70 years living in the United States with a diagnosis of MF, PV, or ET. The survey consisted of ~ 100 questions related to MPN diagnosis, disease-related medical history, MPN-related symptoms and functional status, changes in employment and work productivity, and impact on daily activities since diagnosis. The MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) was used to assess symptom burden. The Work Productivity and Activity Impairment Specific Health Problem questionnaire (WPAI-SHP) was used to assess the effects of MPNs on work productivity and activity (7-day recall) among currently employed respondents. Correlations between MPN-SAF TSS and WPAI-SHP scores were calculated using Spearman's coefficients. RESULTS: Of 904 respondents, 592 were employed (MF, n = 174; PV, n = 248; ET, n = 170) at the time of their MPN diagnosis. Approximately half (50.5%) of the 592 employed survey respondents reported ≥1 change in employment status because of their diagnosis, most commonly "left a job" (30.2%) "went on medical disability leave" (24.8%), and "had reductions in work hours for at least 3 months" (21.8%). Among respondents who remained employed at the time of survey participation (n = 398), mean WPAI-SHP scores were as follows: absenteeism, 6.9%; presenteeism, 27.4%; overall work impairment, 31.1%; and activity impairment, 32.8%. WPAI-SHP scores positively correlated with MPN-SAF TSS (correlation coefficients, 0.37-0.70; P < 0.001). CONCLUSIONS: Half of the employed respondents had an employment status change (eg, leaving a job, medical disability leave, early retirement) because of their disease since the diagnosis. Currently employed respondents reported meaningful impairments in work productivity and activities of daily living that were attributable to their MPNs, and the degree of impairments highlighted the severity of symptom burden.

Cytoreductive treatment patterns among US veterans with polycythemia vera.

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thrombotic and cardiovascular risk, which are key contributors to patient morbidity and mortality. The Veterans Health Administration (VHA) is the largest integrative health network in the United States. Available data concerning patients with PV in this population are limited. METHODS: This retrospective observational study evaluated the characteristics, management, and outcomes of patients with PV in the VHA Medical SAS® Dataset (October 1, 2005, to September 30, 2012). Inclusion criteria were ≥ 2 claims for PV (ie, PV diagnostic code was recorded) ≥30 days apart during the identification period, age ≥ 18 years, and continuous health plan enrollment from ≥12 months before the index date until the end of follow-up. All data were analyzed using descriptive statistics. RESULTS: The analysis included 7718 patients (median age, 64 years; male, 98%; white, 64%). The most common comorbidities before the index date were hypertension (72%), dyslipidemia (54%), and diabetes (24%); 33% had a history of smoking. During the follow-up period (median, 4.8 years), most patients did not receive treatment with cytoreductive therapy, including phlebotomy (53%), or antiplatelet agents, such as aspirin (57%). The thrombotic and cardiovascular event rates per 1000 patient-years were 60.5 and 83.8, respectively. Among patients who received cytoreductive treatment, the thrombotic event rate was 48.9 per 1000 patient-years. The overall mortality rate was 51.2 per 1000 patient-years. CONCLUSION: The notable rates of thrombotic and cardiovascular events observed in this analysis, even among patients receiving cytoreductive treatment, highlight the important unmet clinical needs of patients with PV in the VHA.

Differences in treatment goals and perception of symptom burden between patients with myeloproliferative neoplasms (MPNs) and hematologists/oncologists in the United States: Findings from the MPN Landmark survey.

BACKGROUND: This analysis of the myeloproliferative neoplasm (MPN) Landmark survey evaluated gaps between patient perceptions of their disease management and physician self-reported practices. METHODS: The survey included 813 patient respondents who had MPNs (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]) and 457 hematologist/oncologist respondents who treated patients with these conditions. RESULTS: Greater proportions of physician respondents reported using prognostic risk classifications (MF, 83%; PV, 59%; ET, 77%) compared with patient recollections (MF, 54%; PV, 17%; ET, 31%). Most physician respondents reported that their typical symptom assessments included asking patients about the most important symptoms or a full list of symptoms, whereas many patient respondents reported less specific assessments (eg, they were asked how they were feeling). Many patient respondents did not recognize common symptoms as MPN-related. For example, approximately one-half or more did not believe difficulty sleeping resulted from their MPN (MF, 49%; PV, 64%; ET, 76%). Physician respondents underestimated the proportion of patients who had symptomatic PV or ET at diagnosis compared with patient respondents. There was discordance regarding treatment goals: among patient respondents with MF or PV, "slow/delay progression of condition" was the most important treatment goal, whereas physician respondents reported "symptom improvement" and "prevention of vascular/thrombotic events," respectively. Finally, more than one-third of patient respondents were not "very satisfied" with their physician's overall management/communication. CONCLUSIONS: The care and satisfaction of patients with MPN may be improved with increased patient education and improved patient-physician communication. Cancer 2017;123:449-458. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Changes in quality of life and disease-related symptoms in patients with polycythemia vera receiving ruxolitinib or standard therapy.

OBJECTIVES: Polycythemia vera (PV)-related symptoms may not be adequately controlled with conventional therapy. This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with standard therapy on quality of life (QoL) and symptoms in patients with PV who were hydroxyurea resistant/intolerant. METHODS: In the previously reported primary analysis, ruxolitinib achieved the primary composite endpoint of hematocrit control and ≥35% reduction in spleen volume at Week 32. The current analysis evaluated patient-reported outcomes using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF), the Pruritus Symptom Impact Scale (PSIS), and the Patient Global Impression of Change (PGIC). RESULTS: Compared with standard therapy, ruxolitinib was associated with greater improvements in global health status/QoL, functional subscales, and individual symptom scores of the EORTC QLQ-C30. At Week 32, more patients in the ruxolitinib arm (44%) achieved a ≥10-point improvement in global health status/QoL vs. standard therapy (9%). Improvements in MPN-SAF symptom scores were consistent with improvements in EORTC QLQ-C30, PSIS, and PGIC scores. CONCLUSIONS: Ruxolitinib provides clinically relevant improvements in QoL and ameliorates symptom burden in patients with PV who are hydroxyurea resistant/intolerant.

Independent contribution of A1C, systolic blood pressure, and LDL cholesterol control to risk of cardiovascular disease hospitalizations in type 2 diabetes: an observational cohort study.

BACKGROUND: Cardiovascular disease (CVD) prevention in diabetes requires broad-based treatment of dyslipidemia, hypertension, and hyperglycemia. The independent contribution of all combinations of risk factor control to CVD risk has not been evaluated. OBJECTIVE: To estimate the independent association of control of glycosylated hemoglobin (A1C), systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with risk of cardiovascular disease hospitalization. DESIGN: Non-concurrent longitudinal cohort study. PATIENTS: The study included 26,636 patients with type 2 diabetes who were members of an integrated group model HMO with multiple A1C, SBP, and LDL-C measurements. MAIN MEASURES: Patients were followed for a mean (SD) of 5.6 (2.5) years until they died or disenrolled, or until 31 December 2010. The outcome was a first-observed CVD hospitalization. Using the mean of all A1C, SBP, and LDL-C measures during follow-up, we created dichotomous categories of A1C control (< 7 %), SBP control (< 130 mmHg), and LDL-C control (< 100 mg/dL) to estimate the incidence rate of CVD hospitalization associated with all combinations of risk factor control adjusting for demographic and clinical characteristics. KEY RESULTS: Patients with no controlled risk factors (18.2/1,000 person-years, 95 % CI 16.5-20.2) or with only A1C in control (16.9, 15.0-19.0) had the highest rate of CVD hospitalization, whereas those with all three risk factors controlled (7.2, 6.2-8.4) or with SBP and LDL-C in control (6.1, 5.1-7.2) had the lowest rates. Those with only SBP or LDL-C in control, A1C and SBP controlled, or A1C and LDL-C controlled had statistically similar incidence between the highest and lowest rates. CONCLUSIONS: Maintaining SBP < 130 mmHg or LDL-C < 100 mg/dL was significantly associated with reduced CVD hospitalization risk, especially when both risk factors were well controlled. Maintaining A1C < 7 % was not independently associated with reduced CVD hospitalization risk.

Productivity loss outcomes and costs among patients with cholangiocarcinoma in the United States: an economic evaluation.

BACKGROUND: Cholangiocarcinoma (CCA) is associated with poor prognosis. Healthcare-related management likely presents a substantial economic burden associated with time away from work in patients with CCA. OBJECTIVES: To assess productivity loss, associated indirect costs, and all-cause healthcare resource utilization and costs owing to workplace absenteeism, short-term disability, and long-term disability in CCA patients with work absence and disability benefits eligibility in the United States. METHODS: US retrospective claims data from Merative MarketScan Commercial and Health and Productivity Management Databases. Eligible patients were adults with ≥1 non-diagnostic medical claim for CCA in the index period (1 January 2011-31 December 2019) and had ≥6 months of continuous medical and pharmacy benefit enrolment before and ≥1 month of follow-up and full-time employee work absence and disability benefits eligibility after the index date. Outcomes were assessed in patients with CCA, intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA) in absenteeism, short-term disability, and long-term disability cohorts (measured per patient per month [PPPM] for a month of 21 workdays), with costs standardized to 2019 USD. RESULTS: One thousand and sixty-five patients with CCA were included (iCCA: n = 624 [58.6%]; eCCA: n = 380 [35.7%]). The mean age was 51.9-53.9 years across cohorts. In patients with iCCA and eCCA, respectively, the number of mean all-cause days absent PPPM for illness was 6.0 and 4.3, and 12.9 and 6.6% had ≥1 CCA-related short-term disability claim. Median indirect costs PPPM owing to absenteeism, short-term disability, and long-term disability, respectively, in patients with iCCA were $622, $635, and $690, and $304, $589, and $465 in patients with eCCA. Patients with iCCA vs. eCCA had higher inpatient, outpatient medical, outpatient pharmacy, and all-cause healthcare costs PPPM. CONCLUSIONS: Patients with CCA had high productivity losses, indirect costs, and medical costs. Outpatient services costs contributed greatly to the higher healthcare expenditure observed in patients with iCCA vs. eCCA.

Cholangiocarcinoma (CCA) changes patients' health, lives, finances, and work. We wanted to understand the effect of CCA on work, costs of lost workdays, and costs of healthcare for patients in the US. We looked at health insurance claims for 1,065 adults which included payments requested to insurance providers for covered healthcare from 2011 to 2019. We grouped people in three ways. The "absence group" included 107 people whose work absences we could track. The "short-term leave" (STL) group included 617 people whose jobs allowed short-term medical leave benefits. The "long-term leave" (LTL) group included 549 people whose jobs allowed long-term medical leave benefits. People could belong to more than one group, i.e. a person who had an absence could also take STL or LTL. About two thirds of the employees with CCA in the absence group missed at least 1 day of work because of illness and lost more than 5 workdays per month on average. Work lost for all absences generally costs employers almost $1000 per month. About half of the STL group took short-term leaves. On average, they lost 6­7 workdays per month, costing about $860. About one-tenth of the LTL group took long-term leaves. On average, they lost just over 6 workdays per month, costing about $800. Average total healthcare costs for all groups were about $10,300­$11,200 per month. Overall, people with CCA inside the liver missed more days from work because of illness and had higher total healthcare costs compared to those with CCA outside the liver.

Treatment preferences among patients with mild-to-moderate atopic dermatitis.

Study purpose: New treatments for atopic dermatitis (AD) are emerging; however, little is known about the treatment preferences of patients with mild-to-moderate AD. To measure patients' preferences, a cross-sectional, web-based discrete choice experiment (DCE) survey was developed and administered to 300 adults in the United States with a self-reported physician diagnosis of mild-to-moderate AD.Materials and methods: In the DCE, respondents evaluated pairs of hypothetical AD treatment profiles defined by efficacy, risk, and mode and frequency of administration attributes. The DCE data were analyzed using a random parameters logit model. Subgroup analysis was used to investigate preference heterogeneity.Results: The results revealed achieving clear or almost clear skin within 3-4 months of treatment was the most important attribute relative to all other study attributes. The results indicated that a topical cream applied twice daily was preferred to systemic treatments. Subgroup analysis revealed that respondents with lower self-assessed disease burden were more likely to choose topical over systemic treatments and less averse to the risk of pain, burning, and/or stinging from the medicine (all other treatment features remaining equal) than respondents with higher self-assessed disease burden.Conclusion: The results of this study can help inform shared decision-making to manage mild-to-moderate AD.

Ruxolitinib for myelofibrosis in elderly non-transplant patients: healthcare resource utilization and costs.

AIM: This study evaluated real-world healthcare resource utilization (HCRU), direct costs, and overall survival (OS) of patients who were Medicare beneficiaries and were newly diagnosed with myelofibrosis (MF) who filled ≥1 prescription of ruxolitinib versus those who did not. PATIENTS AND METHODS: This was a study of the US Medicare fee-for-service database. Beneficiaries were aged ≥65 years with an MF diagnosis (index) between January 1, 2012 - December 31, 2017. Data were summarized descriptively. OS was estimated using Kaplan-Meier analysis. RESULTS: Patients with ≥1 prescription fill of ruxolitinib (n = 2,787) had lower mean rates (per patient per month [PPPM]) versus patients who did not fill a prescription for ruxolitinib (n = 7,262) for hospitalizations (0.16 vs 0.32), length of inpatient stay (0.16 vs 2.44 days), emergency department visits (0.10 vs 0.14), physician office visits (4.68 vs 6.25), skilled nursing facility stays (0.02 vs 0.12), home health/durable medical equipment services (0.32 vs 0.47), and hospice visits (0.30 vs 1.70). Monthly medical costs were numerically lower in patients who had ≥1 fill of ruxolitinib versus those who did not fill a prescription for ruxolitinib ($6,553 vs $12,929), largely driven by inpatient costs ($3,428 vs $6,689). Pharmacy costs were $10,065 and $987 in patients who filled versus did not fill ≥1 prescription for ruxolitinib, respectively; total PPPM all-cause healthcare costs were $16,618 and $13,916, respectively. The median OS was 37.5 and 18.7 months for the cohorts of patients who filled versus did not fill ≥1 prescription for ruxolitinib, respectively (hazard ratio = 0.63, 95% CI = 0.59 - 0.67). CONCLUSIONS: Ruxolitinib is associated with reduced HCRU and direct costs of medical care in addition to increased survival, suggesting it to be a cost-effective advance for patients with MF.

Myelofibrosis is a rare bone marrow cancer. People with this disease do not live as long as the general population. They have difficult symptoms, can tire easily, and may have a large spleen that can be uncomfortable. Ruxolitinib is a treatment for myelofibrosis that can improve symptoms and help patients live longer.This study asked how treating patients with ruxolitinib affected three things. (1) How often do they go to a healthcare provider? (2) How much do they spend on their healthcare? (3) How long do they live? The authors looked at Medicare records to answer these questions.The study found that treated patients visited hospitals, doctors' offices, and other services less often. When they did require hospital care, they stayed in the hospital for a shorter amount of time. As a result, treated patients spent about half as much on these services. However, patients treated with ruxolitinib spent more at the pharmacy. Finally, treated patients lived about twice as long as those who were never treated with ruxolitinib. These findings suggest that ruxolitinib is worthwhile for patients with myelofibrosis.

Changes in the incidence and overall survival of patients with myeloproliferative neoplasms between 2002 and 2016 in the United States.

This analysis examined trends in incidence and survival among US adults with myeloproliferative neoplasms, including essential thrombocythemia (ET; n = 14,676), polycythemia vera (PV; n = 15,141), and primary myelofibrosis (PMF; n = 4214), using Surveillance, Epidemiology, and End User Results (SEER) data (SEER 18; 2002-2016). Incidence and survival rates over the study period and by diagnosis year (per 5-year time frames: 2002-2006; 2007-2011; 2012-2016) were assessed. The overall incidence rates (95% CI) were 1.55 (1.52-1.57) for ET, 1.57 (1.55-1.60) for PV, and 0.44 (0.43-0.45) per 100,000 person-years for PMF, with rising ET incidence. Five-year mortality over the study period was 19.2%, 19.0%, and 51.0% for ET, PV, and PMF, respectively. Improved survival over time was observed for PV and PMF, but not for ET. These findings highlight the need for effective ET therapies, as ET incidence has risen without concurrent improvements in survival over the past 2 decades.

Thrombotic events and mortality risk in patients with newly diagnosed polycythemia vera or essential thrombocythemia.

Patients with polycythemia vera (PV) and essential thrombocythemia (ET) have increased thrombotic risk. This retrospective, real-world analysis of Medicare patients (age ≥ 65 years) newly diagnosed with high-risk PV or intermediate-/high-risk ET compared mortality risk among those with versus without thrombotic events during the study period. Patients diagnosed with PV or ET with ≥ 1 inpatient or ≥ 2 outpatient claims (January 1, 2010-December 31, 2017; index was date of first qualifying claim) were included. The study included 50,405 Medicare beneficiaries with PV and 124,569 with ET. During follow-up (median [range]: PV, 34.5 [0-97.3] months; ET, 25.5 [0-97.4] months), 14,334 patients (28.4%) with PV and 30,478 (24.5%) with ET experienced thrombotic events (most commonly ischemic stroke [PV, 46.0%; ET, 42.5%]. Mortality risk was increased for patients with versus without post-index thrombosis for both PV (adjusted hazard ratio [aHR; 95% CI], 18.6 [16.1-21.6]; P < 0.001) and ET (aHR [95% CI], 25.2 [23.1-27.5]; P < 0.001). Median survival was shorter for patients who experienced a thrombotic event ≤ 1 year post-index versus those who did not (PV, 5.1 years vs not reached; ET, 3.7 vs 6.7 years; both P < 0.001). These findings highlight the importance of thrombosis risk mitigation in PV and ET management.

Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheumatoid arthritis: results of an analysis of the literature over the past 16 years.

OBJECTIVE: To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients. METHODS: A systematic literature review was performed using predefined inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNFα inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations. Enrolment start date for each trial was the time metric. The anchor time was the study with the earliest identifiable enrolment start date. RESULTS: 44 primary publications (reporting the primary study endpoint) from 1993 to 2008 met the inclusion criteria. Enrolment start dates of August 1993 and May 1997 were identified as time anchors for the 37 methotrexate-experienced studies and the seven methotrexate-naive studies, respectively. In methotrexate-experienced trials, no significant change was observed over the years included in this study in any inclusion criteria (including swollen joint counts and C-reactive protein (CRP)), but a significant decrease over time was observed in the baseline swollen joint count, CRP and total Sharp or van der Heijde modified Sharp score, but not in baseline tender joint counts. In the methotrexate-naive studies, significant decreases over the years were observed in swollen joint and tender joint inclusion criteria, but not in baseline tender joint count, baseline CRP, CRP inclusion criteria or baseline total Sharp or van der Heijde modified Sharp score. CONCLUSION: Inclusion criteria and baseline characteristics of RA patients enrolled in studies of TNFα inhibitors have changed, with more recent trials enrolling cohorts with lower disease activity, especially in methotrexate-experienced trials.

Real-World Dosing Patterns of Ruxolitinib in Patients With Polycythemia Vera Who Are Resistant to or Intolerant of Hydroxyurea.

INTRODUCTION: Approximately one-quarter of patients with polycythemia vera become resistant to and/or intolerant of hydroxyurea. This analysis characterizes reasons patients were switched from hydroxyurea to ruxolitinib and describes ruxolitinib dosing patterns and outcomes in real-world clinical practice. PATIENTS AND METHODS: This medical chart review of United States community hematology/oncology practices in the Cardinal Health Oncology Provider Extended Network included patients with polycythemia vera who were ≥18 years old, received hydroxyurea for ≥3 months, started ruxolitinib between January 1, 2015 and December 31, 2016, and had ≥2 visits during the subsequent 6 months. Clinical data were collected at predefined intervals from diagnosis to last provider visit. RESULTS: Providers identified 249 patients for inclusion. jcauses of hydroxyurea discontinuation were resistance (78%; frequently for hematocrit ≥45% [79%]) and intolerance (28%; frequently for nausea/vomiting [50%]). Initial ruxolitinib dosing was 10 mg twice daily (recommended dose) in 131 patients (53%). Among these patients, median treatment duration was 29.2 months, 35 (27%) had dose modification (increase, n = 24; decrease, n = 11) and 4 had interruptions within 6 months. The most common reason for dose increase was continued need for phlebotomy (46%); 6 patients had dose reductions owing to reduced platelets. Hematocrit control at initiation and during the first 6 months of ruxolitinib treatment was 15% and 63%, respectively. CONCLUSION: Most patients initiated ruxolitinib upon hydroxyurea resistance. Approximately half initiated ruxolitinib at the recommended dose, 27% of whom experienced dosing modifications within the first 6 months. After switching to ruxolitinib, most patients achieved hematocrit control and continued treatment for extended time frames.

Healthcare resource utilization and costs among patients with steroid-resistant chronic graft-versus-host disease in the United States: a retrospective claims database analysis.

BACKGROUND: Chronic graft-versus-host disease (cGVHD) is the most serious non-relapse complication affecting long-term allogeneic hematopoietic cell transplantation (HCT) survivors. We describe healthcare resource utilization (HCRU) and costs in patients with steroid-resistant (SR) cGVHD versus no GVHD up to 360 and 720 days post-HCT. METHODS: Claims from the Optum Research Database were used to identify patients aged ≥12 years who underwent allogeneic HCT (index date) in the United States from 01 January 2010 to 31 August 2016 with diagnosis of cGVHD (within the study period or unspecified GVHD beyond 120 days post-HCT [SR defined as additional therapy ≥7 days after initiation of systemic steroids]) or no GVHD at any time. All-cause HCRU and costs were compared in patients with SR cGVHD (1-year analysis, n = 296; 2-year analysis, n = 178) versus no GVHD (1-year analysis, n = 227; 2-year analysis, n = 158). RESULTS: Most patients with SR cGVHD (75%) received ≥4 lines of therapy during follow-up. Patients with SR cGVHD had significantly more median office visits (49 vs. 27), outpatient visits (69 vs. 24), emergency department visits (1 vs. 0), and inpatient admissions (2 vs. 1) within 1 year post-HCT versus patients with no GVHD (all p<.001); HCRU was also higher in the 2-year period. Median total all-cause costs were significantly higher (p<.001) for patients with SR cGVHD versus no GVHD in the 1-year ($372,254 vs. $219,593) and 2-year ($532,673 vs. $252,909) follow-up periods. CONCLUSIONS: Patients with SR cGVHD required multiple lines of therapy and used significantly more outpatient and inpatient resources resulting in higher costs versus patients with no GVHD.