Real-world treatment patterns, patient-reported outcomes, and effectiveness of flexibledosing etanercept in patients with plaque psoriasis in Greece.

Etanercept is approved for continuous or intermittent use and flexible dosing in plaque psoriasis (PsO). The objectives of this study were to investigate real-world treatment patterns with etanercept in Greek adults with moderate-to-severe PsO. This non-interventional multicenter study included a retrospective-to-prospective (RP) cohort, previously treated with etanercept for ≥24 months and followed for an additional 6 months, and a biologic-naïve, prospective-only (PO) cohort, followed for 6 months after treatment initiation. Parameters assessed included Psoriasis Area and Severity Index (PASI), percentage of body surface area (BSA) affected, Dermatology Life Quality Index (DLQI), and adverse events (AEs). This study enrolled 123 patients (RP, n = 56; PO, n = 67), who mostly adhered to continuous treatment (RP, 68%; PO, 95%). The two cohorts had similar mean baseline-to-endpoint decreases in PASI (-9.5 vs -10.1) and BSA (-11.9 vs -12.3). The PO-CTP population had a mean DLQI baseline-to-endpoint score decrease of -5.8, which was statistically significant and clinically meaningful. Treatment-emergent AE rates were 58.9% (RP) versus 26.9% (PO). These real-world data suggest a similar effectiveness of continuous and intermittent etanercept treatment in Greek patients with PsO.

Cost-effectiveness Analysis of Lorlatinib in Patients Previously Treated with Anaplastic Lymphoma Kinase Inhibitors for Non-small Cell Lung Cancer in Greece.

Background: Non-small cell lung cancer (NSCLC), which accounts for about 80%-85% of lungcancer cases, is a leading cause of cancer-related death worldwide. Lorlatinib is a potent third-generation anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of patients with advanced, ALK-positive NSCLC previously treated with at least one second-generation ALK tyrosine kinase inhibitor. Objective: The present study assessed the cost-effectiveness of lorlatinib vs pemetrexed with platinum combination of carboplatin or cisplatin (P-ChT) in Greece. Methods: A partitioned survival model with three health states, referring to pre-progression, progressed disease, and death, was locally adapted from a Greek payer perspective over a lifetime horizon. Clinical and safety data and utility values applied in the model were extracted from the literature. A matching-adjusted indirect comparison of lorlatinib and P-ChT was performed. Only direct medical costs (€) from 2020 were included in the analysis. Primary outcomes were patient life years (LYs), quality-adjusted life years (QALYs), total costs, and incremental cost-effectiveness ratios per QALY and LY gained. All future outcomes were discounted at 3.5% per annum. A probabilistic sensitivity analysis was conducted to account for model uncertainty. Results: The analysis showed that, over a lifetime horizon, the estimated total costs of lorlatinib and P-ChT were €81 754 and €12 343, respectively. Lorlatinib was more effective than P-ChT with 2.4 and 1.5 more LYs and QALYs gained, respectively. The generated incremental cost-effectiveness ratios of lorlatinib compared with P-ChT were €28 613 per LY gained and €46 102 per QALY gained. Probabilistic sensitivity analysis confirmed the deterministic results. Conclusion: The present analysis suggests that lorlatinib may be considered as a cost-effective option compared with P-ChT in Greece for the treatment of patients with advanced, ALK-positive NSCLC whose disease has progressed after at least one second-generation ALK tyrosine kinase inhibitor. In addition, this option addresses a significant unmet medical need.

Estimation of the economic burden of atrial fibrillation-related stroke in Greece.

BACKGROUND: Stroke is aleading cause of death and disability, with atrial fibrillation (AF) being among key risk factors and AF-related stroke inflicting significant burden on healthcare systems and society. The present study was undertaken for estimating the total annual socioeconomic burden of AF-related stroke in Greece and identifying the key cost contributors. RESEARCH DESIGN AND METHODS: A cost-of-illness model was developed for estimating the total annual economic burden of AF-related stroke in Greece, from asocietal perspective (year 2018). Atargeted literature review and an advisory board consisting of key experts in the management of AF and AF-related stroke were performed for collecting local resource use and epidemiological data. RESULTS: The total annual socioeconomic burden of AF-related stroke was estimated at €175million, in 2018. Direct and indirect costs accounted for 59% and 41%, respectively. Main contributors were informal care (21.1%), patients' productivity losses (19.7%) and hospitalizations (15.0%), accounting for more than half of the total costs of AF-related stroke events.Conclusion: A F-related stroke imposes asignificant socioeconomic burden in Greece. Despite results relying on estimations, it seems that ensuring efficient reallocation of resources in appropriate prevention and early intervention strategies could decrease AF-related stroke's burden but also enhance healthcare systems' efficiency. ABBREVIATIONS: AF=atrial fibrillation.

Blood pressure variability assessed by office, home, and ambulatory measurements: comparison, agreement, and determinants.

The present study compared the blood pressure variability (BPV) among office (OBP), home (HBP), and ambulatory blood pressure (ABP) measurements and assessed their determinants, as well as their agreement in identifying individuals with high BPV. Individuals attending a hypertension clinic had OBP measurements (2-3 visits) and underwent HBP monitoring (3-7 days, duplicate morning and evening measurements) and ABP monitoring (24 h, 20-min intervals). BPV was quantified using the standard deviation (SD), coefficient of variation (CV), and variability independent of the mean (VIM) using all BP readings obtained by each method. A total of 626 participants were analyzed (age 52.8 ± 12.0 years, 57.7% males, 33.1% treated). Systolic BPV was usually higher than diastolic BPV, and out-of-office BPV was higher than office BPV, with ambulatory BPV giving the highest values. BPV was higher in women than men, yet it was not different between untreated and treated individuals. Associations among BPV indices assessed using different measurement methods were weak (r 0.1-0.3) but were stronger between out-of-office BPV indices. The agreement between methods in detecting individuals with high BPV was low (30-40%) but was higher between out-of-office BPV indices. Older age was an independent determinant of increased OBP variability. Older age, female sex, smoking, and overweight/obesity were determinants of increased out-of-office BPV. These data suggest that BPV differs with different BP measurement methods, reflecting different pathophysiological phenomena, whereas the selection of the BPV index is less important. Office and out-of-office BP measurements appear to be complementary methods in assessing BPV.

Two Sides of the Same Coin? A Dual Multiple Criteria Decision Analysis of Novel Treatments Against Rheumatoid Arthritis in Physicians and Patients.

PURPOSE: Available treatment options for rheumatoid arthritis (RA) differ in important aspects. In this sense, each RA treatment option is accompanied by a spectrum of characteristics that collectively constitute its comprehensive "value," as viewed from the physician's or the patient's perspective. The objective of this study was to perform a multiple criteria decision analysis of different RA treatments from the perspective of physicians and patients and to outline the respective aspects of value for each treatment METHODS: A literature review was performed for constructing a set of criteria (N = 8) for the multiple criteria decision analysis. Workshops for the elicitation of preferences occurred separately for physicians and patients. A performance matrix was populated via 2 network meta-analyses plus converged clinical opinion. Criteria were hierarchically classified by application of pairwise comparisons, and criteria weights were attributed by point allocation through convergence of opinions. Performances in both panels were scored by using a 100-point scale. A linear additive value function was used for the calculation of total value estimates. FINDINGS: Both panels provided their consensus. The hierarchical classification of attributes from the physician perspective placed the highest values on the criteria of severe adverse events, clinical efficacy, route of administration, and cost per year for the third-party payer. From the patient perspective, the highest ranking criteria were clinical efficacy, severe adverse events, percentage of patients remaining with the same targeted immune modulator for 1 year ("drug survival"), and cost per year for the third-party payer. IMPLICATIONS: In an era of multiple options and varying preferences, RA treatments must be evaluated by taking into consideration patients' preferences as well, as to cover the full spectrum of value elements rather than simply clinical outcomes. The results of this analysis show that physicians and patients share similarities but also marked differences in terms of the aspects of treatment that they perceive as more valuable.

Validation of the professional device for blood pressure measurement Microlife WatchBP Office in adults and children according to the American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization standard.

OBJECTIVE: To assess the accuracy of the professional oscillometric blood pressure (BP) monitor Microlife WatchBP Office in adults and children according to the American National Standards Institute/Association for the Advancement of Medical Instrumentation/International Organization for Standardization (ANSI/AAMI/ISO) 81060-2:2013 standard. METHODS: Adults and children (aged 3-12 years) were recruited to fulfil the age, sex, BP and cuff distribution criteria of the ANSI/AAMI/ISO standard using the same-arm sequential BP measurement method. Three cuffs of the test device were used for arm circumferences of 14-22, 22-32 and 32-42 cm. RESULTS: A total of 115 participants were recruited and 88 were included in the analysis (51 adults and 37 children). For criterion 1, the mean±SD of the differences between the test device and reference BP was -1.0±7.0/-4.7±5.4 mmHg (systolic/diastolic). For criterion 2, the SD of the averaged BP differences between the test device and reference per participant was 5.15/4.77 mmHg (systolic/diastolic). CONCLUSION: The professional Microlife WatchBP Office BP monitor fulfilled the requirements of the ANSI/AAMI/ISO validation standard for adults and children and can be recommended for clinical use.

Cost-effectiveness of Ingenol Mebutate Gel for the Treatment of Actinic Keratosis in Greece.

PURPOSE: The present study aimed to perform a cost-effectiveness analysis of ingenol mebutate (IM) versus other topical alternatives for the treatment of actinic keratosis (AK). METHODS: The analysis used a decision tree to calculate the clinical effects and costs of AK first-line treatments, IM (2-3 days), diclofenac 3% (for 8 or 12 weeks), imiquimod 5% (for 4 or 8 weeks), during a 24-month horizon, using discrete intervals of 6 months. A hypothetical cohort of immunocompetent adult patients with clinically confirmed AK on the face and scalp or trunk and extremities was considered. Clinical data on the relative efficacy were obtained from a network meta-analysis. Inputs concerning resource use derived from an expert panel. All costs were calculated from a Greek third-party payer perspective. FINDINGS: IM 0.015% and 0.05% were both cost-effective compared with diclofenac and below a willingness-to-pay threshold of €30,000 per quality-adjusted life-year (QALY) (€199 and €167 per QALY, respectively). Comparing IM on the face and scalp AK lesions for 3 days versus imiquimod for 4 weeks resulted in an incremental cost-effectiveness ratio of €10,868 per QALY. IM was dominant during the 8-week imiquimod period. IM use on the trunk and extremities compared with diclofenac (8 or 12 weeks) led to incremental cost-effectiveness ratios estimated at €1584 and €1316 per QALY accordingly. Results remained robust to deterministic and probabilistic sensitivity analyses. IMPLICATIONS: From a social insurance perspective in Greece, IM 0.015% and IM 0.05% could be the most cost-effective first-line topical field treatment options in all cases for AK treatment.

Cost Effectiveness of Apixaban versus Warfarin or Aspirin for Stroke Prevention in Patients with Atrial Fibrillation: A Greek Perspective.

BACKGROUND: Strokes attributed to atrial fibrillation (AF) represent a major cause of adult disability and a great burden to society and healthcare systems. OBJECTIVES: Our objective was to assess the cost effectiveness of apixaban, a direct acting oral anticoagulant (DOAC), versus warfarin or aspirin for patients with AF in the Greek healthcare setting. METHODS: We used a previously published Markov model to simulate clinical events for patients with AF treated with apixaban, the vitamin K antagonist (VKA) warfarin, or aspirin. Clinical events (ischemic and hemorrhagic stroke, intracranial hemorrhage, other major bleed, clinically relevant non-major bleed, myocardial infarction, and cardiovascular [CV] hospitalizations) were modeled using efficacy data from the ARISTOTLE and AVERROES clinical trials. The cohort's baseline characteristics also sourced from these trials. Among VKA-suitable patients, 64.7% were men with a mean age of 70 years and average CHADS2 (cardiac failure, hypertension, age, diabetes, stroke2) score of 2.1, whereas 58.5% of VKA-unsuitable patients were men with a mean age of 70 years and a CHADS2 score of 2.0. A panel of experts (cardiologists and internists) provided information on the resource use associated with the management of AF. Cost calculations reflect the local clinical setting and a third-party payer perspective (€, discounted at 3%). RESULTS: Based on a simulation of 1000 VKA-suitable patients over a lifetime horizon, the use of apixaban versus warfarin resulted in 26 fewer strokes and systemic embolisms in total, 65 fewer bleeds, 41 fewer myocardial infarctions, and 29 fewer CV-related deaths, with an incremental cost-effectiveness ratio (ICER) of €14,478/quality-adjusted life-year (QALY). For VKA-unsuitable patients, apixaban versus aspirin resulted in 72 fewer strokes and systemic embolisms and 57 fewer CV-related deaths, with an ICER of €7104/QALY. Sensitivity analyses indicated that results were robust. CONCLUSIONS: Based on the present analysis, apixaban represents a cost-effective treatment option versus warfarin and aspirin for the prevention of stroke in patients with AF from a Greek healthcare payer perspective over a lifetime horizon.

Treatment with the first TNF inhibitor in rheumatoid arthritis patients in the Hellenic Registry of Biologic Therapies improves quality of life especially in young patients with better baseline functional status.

OBJECTIVES: To assess in daily practice in patients with rheumatoid arthritis (RA) the effect of treatment with first tumour necrosis factor-α inhibitor (TNFi) in quality of life (Qol), disease activity and depict possible baseline predictors for gains in Qol. METHODS: Patients followed prospectively by the Hellenic Registry of Biologic Therapies were analysed. Demographics were recorded at baseline, while RA-related characteristics at baseline and every 6 months. Paired t-tests were used to detect divergences between patient-reported (Health Assessment Questionnaire (HAQ), EuroQol (EQ-5D)) and clinical tools (Disease Activity Score-28 joints (DAS28)). Clinical versus self-reported outcomes were examined via cross-tabulation analysis. Multiple regression analysis was performed for identifying baseline predictors of improvements in QALYs. RESULTS: We analysed 255 patients (age (mean±SD) 57.1±13.0, disease duration 9.2±9.1 years, prior non-biologic disease-modifying anti-rheumatic drugs 2.3±1.2). Baseline EQ-5D, HAQ and DAS28 were 0.36 (0.28), 1.01 (0.72) and 5.9 (1.3), respectively, and were all significantly improved after 12 months (0.77 (0.35), 0.50 (0.66), 3.9 (1.5), respectively, p<0.05 for all). 90% of patients who improved from high to a lower DAS28 status (low-remission or moderate) had clinically important improvement in Qol (phi-coefficient=0.531,p<0.05). Independent predictors of gains in Qol were lower baseline HAQ, VAS global and younger age (adjusted R2=0.27). CONCLUSIONS: In daily practice TNFi improve both disease activity and Qol for the first 12 months of therapy. 90% of patients who improved from high to a lower DAS28 status had clinically important improvement in Qol. Younger patients starting with lower HAQ and VAS global are more likely to benefit.

How peptide technology has improved costs and outcomes in patients with heart failure.

INTRODUCTION: Heart failure (HF) is characterized by substantial health and economic burden, mainly attributed to increased hospitalizations and readmissions. Its diagnosis remains challenging due to the non-specific nature of the initial symptoms of the disease. Recently, scientific evidence has highlighted the potential of natriuretic peptides (NP) in improving the diagnosis and prognosis of HF and, by extension, in restraining healthcare costs. The present review aimed at providing evidence of their optimal use in terms of economic and health outcomes. AREAS COVERED: Systematic literature research limited to studies published from February 2006 to February 2016 was performed with the aim of identifying and analyzing all cost-effectiveness and other economic evaluation studies that investigated the economic and health outcomes of NPs use as screening and management tools for HF. Expert commentary: NP testing either added in the standard of care, or substituting frequently used diagnostic procedures for the diagnosis and management of HF, regardless of the healthcare setting of interest, was proved to be a valid tool for clinical decision-making. Moreover it was associated with improved patient outcomes and important cost-savings mainly attributed to lower admission and readmission rates, shorter hospitalization length and improved health-related quality of life.

Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement: current status and future directions - Position statement of the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability.

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Relationship between office and home blood pressure with increasing age: The International Database of HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO).

Home blood pressure (HBP) measurements are known to be lower than conventional office blood pressure (OBP) measurements. However, this difference might not be consistent across the entire age range and has not been adequately investigated. We assessed the relationship between OBP and HBP with increasing age using the International Database of HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO). OBP, HBP and their difference were assessed across different decades of age. A total of 5689 untreated subjects aged 18-97 years, who had at least two OBP and HBP measurements, were included. Systolic OBP and HBP increased across older age categories (from 112 to 142 mm Hg and from 109 to 136 mm Hg, respectively), with OBP being higher than HBP by ∼7 mm Hg in subjects aged >30 years and lesser in younger subjects (P=0.001). Both diastolic OBP and HBP increased until the age of ∼50 years (from 71 to 79 mm Hg and from 66 to 76 mm Hg, respectively), with OBP being consistently higher than HBP and a trend toward a decreased OBP-HBP difference with aging (P<0.001). Determinants of a larger OBP-HBP difference were younger age, sustained hypertension, nonsmoking and negative cardiovascular disease history. These data suggest that in the general adult population, HBP is consistently lower than OBP across all the decades, but their difference might vary between age groups. Further research is needed to confirm these findings in younger and older subjects and in hypertensive individuals.

Association of Central Versus Brachial Blood Pressure With Target-Organ Damage: Systematic Review and Meta-Analysis.

Accumulating evidence suggests that central blood pressure (BP) may reflect the hemodynamic stress on target organs more accurately than brachial BP. A systematic review assessing the relationship of central versus brachial BP with preclinical target-organ damage was performed. Meta-analysis of cross-sectional data showed that central compared with brachial systolic BP was more closely associated with (1) left ventricular mass index (12 studies, n=6431; weighted age [SD], 49.9 [13.1] years; 51% hypertensives): pooled correlation coefficients r=0.30; 95% confidence interval (CI), 0.23-0.37 versus r=0.26; 95% CI, 0.19-0.33, respectively; P<0.01 for difference; (2) carotid intima-media thickness (7 studies, n=6136; weighted age, 55.6 [13.2] years; 48% hypertensives): r=0.27; 95% CI, 0.19-0.34 versus r=0.23; 95% CI, 0.16-0.30, respectively; P<0.01 for difference; (3) pulse-wave velocity (14 studies, n=3699; weighted age, 53.9 [13.3] years; 53% hypertensives): r=0.42; 95% CI, 0.37-0.47 versus r=0.39; 95% CI, 0.33-0.45, respectively; P<0.01 for difference. Four studies assessing urine albumin excretion (n=3718; weighted age, 56.4 [5] years; 69% hypertensives) reported similar correlations (P=not significant) with central (r=0.22; 95% CI, 0.14-0.29) and brachial systolic BP (r=0.22; 95% CI, 0.12-0.32). Similar findings were observed for central compared with brachial pulse pressure in terms of relationship with target-organ damage. Metaregression analyses did not reveal any significant effect of age. In conclusion, central compared with brachial BP seems to be more strongly associated with most of the investigated indices of preclinical organ damage.

Determinants of the direct cost of heart failure hospitalization in a public tertiary hospital.

BACKGROUND: Heart failure (HF) is the first reason for hospital admission in the elderly and represents a major financial burden, the greatest part of which results from hospitalization costs. We sought to analyze current HF hospitalization-related expenditure and identify predictors of cost in a public tertiary hospital in Europe. METHOD: We performed a retrospective chart review of 197 consecutive patients, aged 56±16years, 80% male, with left ventricular ejection fraction (LVEF) of 30±10%, hospitalized for HF in a major university hospital in Athens, Greece. The survey involved the number of hospitalization days, laboratory investigations and medical therapies. Patients who were hospitalized in CCU/ICU or underwent interventional procedures or device implantations were excluded from analysis. Costs were estimated based on the Greek healthcare system perspective in 2013. RESULTS: Patients were hospitalized for a median of 7 days with a total direct cost of €3198±3260/patient. The largest part of the expenses (79%) was attributed to hospitalization (ward), while laboratory investigations and medical treatment accounted for 17% and 4%, respectively. In multivariate analysis, pre-admission New York Heart Association NYHA class (p=0.001), serum creatinine (p=0.003) and NT-proBNP (p=0.004) were significant independent predictors of hospitalization cost. CONCLUSION: Direct cost of HF hospitalization is high particularly in patients with more severe symptoms, profound neurohormonal activation and renal dysfunction. Strategies to lower hospitalization rates are warranted in the current setting of financial constraints faced by many European countries.

Quantifying the economic benefits of prevention in a healthcare setting with severe financial constraints: the case of hypertension control.

Hypertension significantly contributes to the increased cardiovascular morbidity and mortality, thus leading to rising healthcare costs. The objective of this study was to quantify the clinical and economic benefits of optimal systolic blood pressure (SBP), in a setting under severe financial constraints, as in the case of Greece. Hence, a Markov model projecting 10-year outcomes and costs was adopted, in order to compare two scenarios. The first one depicted the "current setting", where all hypertensives in Greece presented an average SBP of 164 mmHg, while the second scenario namely "optimal SBP control" represented a hypothesis in which the whole population of hypertensives would achieve optimal SBP (i.e. <140 mmHg). Cardiovascular events' occurrence was estimated for four sub-models (according to gender and smoking status). Costs were calculated from the Greek healthcare system's perspective (discounted at a 3% annual rate). Findings showed that compared to the "current setting", universal "optimal SBP control" could, within a 10-year period, reduce the occurrence of non-fatal events and deaths, by 80 and 61 cases/1000 male smokers; 59 and 37 cases/1000 men non-smokers; whereas the respective figures for women were 69 and 57 cases/1000 women smokers; and accordingly, 52 and 28 cases/1000 women non-smokers. Considering health expenditures, they could be reduced by approximately €83 million per year. Therefore, prevention of cardiovascular events through BP control could result in reduced morbidity, thereby in substantial cost savings. Based on clinical and economic outcomes, interventions that promote BP control should be a health policy priority.

Cost estimation of hypertension management based on home blood pressure monitoring alone or combined office and ambulatory blood pressure measurements.

This study aims at estimating the resources consumed and subsequent costs for hypertension management, using home blood pressure (BP) monitoring (HBPM) alone versus combined clinic measurements and ambulatory blood pressure monitoring (C/ABPM). One hundred sixteen untreated hypertensive subjects were randomized to use HBPM or C/ABPM for antihypertensive treatment initiation and titration. Health resources utilized within 12-months follow-up, their respective costs, and hypertension control were assessed. The total cost of the first year of hypertension management was lower in HBPM than C/ABPM arm (€1336.0 vs. €1473.5 per subject, respectively; P < .001). Laboratory tests' cost was identical in both arms. There was no difference in achieved BP control and drug expenditure (HBPM: €233.1 per subject; C/ABPM: €247.6 per subject; P = not significant), whereas the cost of BP measurements and/or visits was higher in C/ABPM arm (€393.9 vs. €516.9, per patient, respectively P < .001). The cost for subsequent years (>1) was €348.9 and €440.2 per subject, respectively for HBPM and C/ABPM arm and €2731.4 versus €3234.3 per subject, respectively (P < .001) for a 5-year projection. HBPM used alone for the first year of hypertension management presents lower cost than C/ABPM, and the same trend is observed in 5-year projection. The results on the resources consumption can be used to make cost estimates for other health-care systems.