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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.

Recruitment of individuals with rare diseases for studies of real-world patient-reported outcomes is limited by small base populations. Myeloproliferative neoplasms (MPNs) are a group of rare, chronic, hematologic malignancies. In this study, recruitment strategies and geographic representativeness from the Living with MPNs survey are reported. The Living with MPNs online cross-sectional survey was conducted between April and November 2016. Individuals 18 to 70 years of age living in the United States and diagnosed with an MPN were eligible to participate. Recruitment approaches included direct contact via emails and postcards; posts on MPN-focused social media and patient advocacy websites; postcard mailings to doctors' offices; and advertisements on medical websites, Google, and Facebook. Geographic representativeness was assessed based on the number of survey respondents living in each state or the District of Columbia and by the number of survey respondents per 10 million residents. A total of 904 respondents with MPNs completed the survey. The recruitment method yielding the greatest number of respondents was advertisements on MPN-focused social media (47.6% of respondents), followed by emails (35.1%) and postcards (13.9%) sent through MPN advocacy groups. Home state information was provided by 775 respondents from 46 states (range of respondents per state, 1-89). The number of respondents per 10 million residents in the 46 states with respondents ranged from 12.1 to 52.7. Recruitment using social media and communications through patient groups and advocacy organizations are effective in obtaining geographically representative samples of individuals with MPNs in the United States. These approaches may also be effective in other rare diseases.

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 × 10 9 /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.

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.

ABSTRACT 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.

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.

Background Patients with polycythemia vera (PV) have a higher mortality risk compared with the general population, primarily driven by cardiovascular disease, thrombotic events (TEs), and hematologic transformations. The goal of risk-adapted therapy in PV is prevention of TEs. Current treatment recommendations indicate that high-risk patients (aged ≥ 60 years and/or with history of TEs) should be managed with cytoreductive medications, phlebotomy, and low-dose aspirin. This noninterventional study was conducted to describe real-world cytoreductive medication treatment in adult patients with PV, stratified by risk, in the United States. Methods This retrospective analysis used claims data from the Truven Health MarketScan ® database. Inclusion criteria were ≥ 2 nondiagnostic claims for PV ≥ 30 days apart, age ≥ 18 years, continuous enrollment during the preindex period (January 1 to December 31, 2012), and continuous enrollment or death during the postindex period (January 1, 2013, to December 31, 2014). Assessments included patient demographics, clinical characteristics, and treatment with cytoreductive medications. Results A total of 2856 patients were identified for this analysis, including 1823 with high-risk PV and 1033 with low-risk PV. Mean (SD) age was 62.5 (13.5) years, and 65.9% of patients were male. Preindex comorbid conditions of interest were more common in high-risk than low-risk patients, including hypertension (65.0% vs 43.1%), type 2 diabetes (21.7% vs 10.1%), and congestive heart failure (6.6% vs 0.6%). Among patients who received preindex cytoreductive therapy, the most commonly used medications in high-risk (n = 666) and low-risk (n = 160) patients were hydroxyurea (94.7 and 87.5%, respectively), anagrelide (7.4 and 11.9%), and interferon (1.7 and 4.4%). Among patients who initiated cytoreductive therapy postindex, the most commonly used medications in high-risk (n = 100) and low-risk (n = 35) patients were hydroxyurea (97.0 and 91.4%, respectively), anagrelide (4.0 and 2.9%), and interferon (2.0 and 8.6%). Overall, 42.0% of high-risk and 18.9% of low-risk patients received cytoreductive medication during the preindex or postindex periods. Conclusions Despite consistent guideline recommendations for cytoreductive therapy in patients with high-risk PV, this analysis revealed that only a minority of these patients received cytoreductive medication. A notable proportion of high-risk patients with PV would likely benefit from a revised treatment plan that aligns with current guidelines.

Abstract 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. This article analyzes trends in incidence, prevalence, and mortality rates of cholangiocarcinoma to assess whether rates continue to rise in the US and contributing factors that may be influencing current rates, including changing incidence of cancers of unknown primary.

Abstract Background There is limited evidence regarding the economic burden, treatment patterns, and overall survival (OS) of patients with cholangiocarcinoma (CCA) and cancer of unknown primary (CUP) who initiated the FGFR inhibitor pemigatinib. Patients and Methods We used the Komodo Healthcare Map to identify patients with CCA who initiated pemigatinib between 4/17/2020 and 5/31/2023. Follow-up began at initiation and lasted ≥ 1 month. Outcomes included health care resource utilization (HCRU), costs, treatment patterns, and OS. Results Two hundred twenty-one patients were included: 78 patients (35.3%) with CUP (median follow-up, 5.9 months) and 143 patients (64.7%) without CUP (median follow-up, 7.3 months). Pemigatinib was similarly well-tolerated in CUP vs non-CUP. Discontinuation was observed in 43.6% vs 49.0% (P = .445). Medication possession ratio ≥ 0.80 was achieved by 71.6% vs 67.2% (P = .504). CUP was associated with significantly higher prevalence of metastatic disease (100.0% vs 63.6%), per patient per month (PPPM) ambulatory HCRU (8.2 vs 5.5), and ambulatory costs ($8584 vs $5308). Medical costs averaged $13 444 vs $9881 PPPM for CUP and non-CUP, respectively (P = .066). Median OS was significantly shorter with CUP (10.2 vs 30.7 months). Conclusion Although pemigatinib was similarly well-tolerated regardless of CUP status, patients with CUP incurred greater ambulatory burden and had poorer OS. Patients with CUP were more likely to have evidence of metastatic disease at pemigatinib initiation, which may help explain these results. With the advent of targeted treatments for gene-altered CCA, reflexive genomic testing should be encouraged for all patients with CUP. Graphical Abstract Graphical Abstract

There is limited evidence regarding the economic burden, treatment patterns, and overall survival (OS) of patients with cholangiocarcinoma (CCA) and cancer of unknown primary (CUP) who initiated the FGFR inhibitor pemigatinib.A. BACKGROUNDThere is limited evidence regarding the economic burden, treatment patterns, and overall survival (OS) of patients with cholangiocarcinoma (CCA) and cancer of unknown primary (CUP) who initiated the FGFR inhibitor pemigatinib.We used the Komodo Healthcare Map to identify patients with CCA who initiated pemigatinib between 4/17/2020-5/31/2023. Follow-up began at initiation and lasted ≥ 1 month. Outcomes included health care resource utilization (HCRU), costs, treatment patterns, and OS.B. PATIENTS AND METHODSWe used the Komodo Healthcare Map to identify patients with CCA who initiated pemigatinib between 4/17/2020-5/31/2023. Follow-up began at initiation and lasted ≥ 1 month. Outcomes included health care resource utilization (HCRU), costs, treatment patterns, and OS.221 patients were included: 78 patients (35.3%) with CUP (median follow-up, 5.9 months) and 143 patients (64.7%) without CUP (median follow-up, 7.3 months). Pemigatinib was similarly well-tolerated in CUP vs non-CUP. Discontinuation was observed in 43.6% vs 49.0% (P = 0.445). Medication possession ratio ≥ 0.80 was achieved by 71.6% vs 67.2% (P = 0.504). CUP was associated with significantly higher prevalence of metastatic disease (100.0% vs 63.6%), per patient per month (PPPM) ambulatory HCRU (8.2 vs 5.5), and ambulatory costs ($8,584 vs $5,308). Medical costs averaged $13,444 vs $9,881 PPPM for CUP and non-CUP, respectively (P = 0.066). Median OS was significantly shorter with CUP (10.2 vs 30.7 months).C. RESULTS221 patients were included: 78 patients (35.3%) with CUP (median follow-up, 5.9 months) and 143 patients (64.7%) without CUP (median follow-up, 7.3 months). Pemigatinib was similarly well-tolerated in CUP vs non-CUP. Discontinuation was observed in 43.6% vs 49.0% (P = 0.445). Medication possession ratio ≥ 0.80 was achieved by 71.6% vs 67.2% (P = 0.504). CUP was associated with significantly higher prevalence of metastatic disease (100.0% vs 63.6%), per patient per month (PPPM) ambulatory HCRU (8.2 vs 5.5), and ambulatory costs ($8,584 vs $5,308). Medical costs averaged $13,444 vs $9,881 PPPM for CUP and non-CUP, respectively (P = 0.066). Median OS was significantly shorter with CUP (10.2 vs 30.7 months).Although pemigatinib was similarly well-tolerated regardless of CUP status, patients with CUP incurred greater ambulatory burden and had poorer OS. Patients with CUP were more likely to have evidence of metastatic disease at pemigatinib initiation, which may help explain these results. With the advent of targeted treatments for gene-altered CCA, reflexive genomic testing should be encouraged for all patients with CUP.D. CONCLUSIONAlthough pemigatinib was similarly well-tolerated regardless of CUP status, patients with CUP incurred greater ambulatory burden and had poorer OS. Patients with CUP were more likely to have evidence of metastatic disease at pemigatinib initiation, which may help explain these results. With the advent of targeted treatments for gene-altered CCA, reflexive genomic testing should be encouraged for all patients with CUP.