Cost-Effectiveness of Recombinant Factor IX Fc Prophylaxis and Recombinant Factor IX On-Demand Treatment in Patients with Haemophilia B Without Inhibitors.

INTRODUCTION: Recombinant factor IX (rFIX) and recombinant FIX Fc fusion protein (rFIXFc) are standard half-life and extended half-life FIX replacement therapies, respectively, and represent established treatment options indicated for adults and children with haemophilia B. These FIX replacement therapies can be administered as prophylaxis (to prevent bleeding) or 'on-demand' (to stop bleeding). This analysis aimed to estimate the cost-effectiveness of once-weekly prophylaxis with rFIXFc versus on-demand treatment with rFIX in patients with haemophilia B without inhibitors in the Italian healthcare setting. METHODS: A Markov model was developed to assess a hypothetical cohort of adolescent or adult male patients (≥ 12 years) with haemophilia B (FIX level of ≤ 2 IU/dL) without inhibitors. Model inputs were derived from the pivotal phase 3 clinical studies for rFIXFc and rFIX, published literature and assumptions when published data were unavailable. The model employed a lifelong time horizon with 6-monthly transitions between health states, and it estimated total costs, total quality-adjusted life years (QALYs), number of bleeds, number of surgeries and incremental cost-effectiveness ratio. RESULTS: rFIXFc prophylaxis was associated with lower total costs per patient (€5,308,625 versus €6,564,510) and greater total QALYs per patient (15.936 versus 11.943) compared with rFIX on-demand; rFIXFc prophylaxis was therefore the dominant treatment strategy. The model also demonstrated that rFIXFc prophylaxis was associated with fewer incremental bleeds (- 682.29) and surgeries (- 0.39) compared with rFIX on-demand. CONCLUSIONS: rFIXFc prophylaxis provides improved health outcomes and lower costs, and represents a cost-effective treatment option compared with rFIX on-demand for adolescent and adult male patients with haemophilia B. This comparative assessment of cost-effectiveness should help to inform both clinicians and healthcare policy makers when making treatment decisions for patients with haemophilia B.

An Economic Comparison of Treatment Strategies with Anakinra in Systemic Juvenile Idiopathic Arthritis (sJIA).

INTRODUCTION: Systemic juvenile idiopathic arthritis (sJIA) is a rare, complex autoinflammatory disease with substantial morbidity, often characterized by fever, rash, and muscle pain, amongst other symptoms. Biologic agents, such as anakinra, have been successfully used to treat patients internationally, but their usage in some regions is limited to patients that have failed to achieve clinically inactive disease with corticosteroids and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Use of anakinra early in the disease course leads to better clinical outcomes; however, longer-term costs for this treatment strategy have not been established. This study compares the economic implications of first-line versus later-line availability of anakinra for patients with sJIA. METHODS: Data for patients treated with first-line anakinra were identified from a single-center, prospective study and compared to a combination of published trial and economic evaluation information to facilitate a comparison to later-line anakinra (ie, following corticosteroids + csDMARDs). Costs were estimated for product acquisition and medical resource utilization (MRU), including planned outpatient visits and unplanned hospital admissions. Total costs over a 5-year horizon were compared. RESULTS: Total 5-year product acquisition cost for the first-line anakinra strategy was €24,021, and for later-line anakinra was €20,471. The corresponding MRU costs were €19,197 (first-line) versus €25,425 (later-line). Overall 5-year costs (product acquisition and MRU) were lower for the first-line strategy (€43,218 versus €45,896). CONCLUSION: The use of anakinra for patients with sJIA in the first-line setting is efficacious to induce and sustain inactive disease, and the findings of this study show that this treatment strategy leads to cost savings through reduced medical expenditure.

Influence of Polypharmacy on the Effectiveness and Safety of Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation.

STUDY OBJECTIVE: Patients with nonvalvular atrial fibrillation (NVAF) often have multiple comorbidities requiring concomitant medications in addition to their oral anticoagulant (OAC). The objective of this study was to evaluate the impact of polypharmacy on the effectiveness and safety of rivaroxaban versus warfarin in patients with NVAF managed in routine clinical practice. DESIGN: Retrospective claims analysis. DATA SOURCE: United States Truven MarketScan database (November 2012-March 2017). PATIENTS: Adults who were OAC naïve during the 12 months before the day of the first qualifying rivaroxaban or warfarin dispensing (index date); had at least two International Classification of Diseases, Ninth or Tenth Revision diagnosis codes for atrial fibrillation without codes suggesting valvular heart disease; had at least 12 months of continuous insurance coverage prior to the qualifying OAC dispensing; and were experiencing polypharmacy (concomitant prescription claims for five or more unique chronic medication claims) were included. Patients who had concomitant prescription claims for ≥ 10 unique chronic medication claims constituted the substantial polypharmacy cohort used in the secondary analysis. Patients receiving rivaroxaban were propensity-score matched in a 1:1 ratio to patients receiving warfarin (13,981 patients in each polypharmacy OAC group, and 1765 patients in each substantial polypharmacy OAC group). MEASUREMENTS AND MAIN RESULTS: Patients were followed until occurrence of an event (stroke or systemic embolism [SSE] combined [primary effectiveness outcome] or major bleeding [primary safety outcome]), OAC discontinuation or switch (30-day permissible gap), insurance disenrollment, or end of follow-up period. Rates of SSE, ischemic stroke, and major bleeding were compared by using Cox regression, reported as hazard ratios (HRs) and 95% confidence intervals (CIs). In patients with NVAF taking five or more chronic medications, rivaroxaban was associated with a 34% (95% CI 12-50) and 40% (95% CI 16-57) hazard reduction of SSE and ischemic stroke, respectively. Occurrence of major bleeding was similar between OAC cohorts (HR 1.08, 95% CI 0.92-1.28). A secondary analysis in patients with NVAF with substantial polypharmacy (taking ≥ 10 chronic medications) was also performed. Similar trends in SSE (HR 0.44), ischemic stroke alone (HR 0.62), and major bleeding (HR 1.07) were observed in patients with NVAF who had substantial polypharmacy, although 95% CIs crossed 1.0 for each outcome in this smaller study cohort. CONCLUSION: This real-world study suggests that in the setting of polypharmacy and NVAF, rivaroxaban is an effective and safe alternative to warfarin.

Effectiveness and safety of rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation and heart failure.

AIMS: Heart failure (HF) is a common co-morbidity in non-valvular atrial fibrillation (NVAF) patients and a potent risk factor for stroke, bleeding, and a decreased time-in-therapeutic range with warfarin. We assessed the real-world effectiveness and safety of rivaroxaban and warfarin in NVAF patients with co-morbid HF. METHODS AND RESULTS: Using US Truven MarketScan Commercial and Medicare supplemental database claims data from 11/2011 to 12/2016, we identified oral anticoagulant (OAC)-naïve NVAF patients with HF (International Classification of Diseases, 10th Revision codes of I50 or I09.81) and ≥12 months of insurance coverage prior to the qualifying OAC dispensing. Rivaroxaban users (20 or 15 mg once daily) were 1:1 propensity score matched to warfarin users, with residual absolute standardized differences <0.1 being achieved for all covariates after matching. Patients were followed up until an event, OAC discontinuation/switch, insurance disenrolment, or end of follow-up. Rates [events per 100 person-years (PYs) of follow-up] for stroke or systemic embolism and major bleeding (using the Cunningham algorithm) were compared between the matched cohorts using Cox proportion hazard regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). We matched 3418 rivaroxaban (32% receiving the reduced dose) and 3418 warfarin users with NVAF and HF with a median (interquartile range) available follow-up of 1.4 (0.6, 2.5) years. Median age was 74 (63, 82) years, and median CHA2 DS2 -VASc and HASBLED scores were 4 (3, 5) and 2 (2, 3). Common HF medications included beta-blockers (64%), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (62%), loop diuretics (46%), digoxin (11%), and aldosterone receptor antagonists (10%). The hazard of developing stroke or systemic embolism (0.98 events/100PY vs. 1.28 events/100PY; HR = 0.82, 95% CI = 0.47-1.44), ischaemic stroke (0.70 events/100PY vs. 1.02 events/100PY; HR = 0.77, 95% CI = 0.41-1.46), or major bleeding (3.86 events/100PY vs. 4.23 events/100PY; HR = 0.98, 95% CI = 0.73-1.31) was not found to be different between rivaroxaban and warfarin users. Intracranial haemorrhage was infrequent in both cohorts and numerically less with rivaroxaban (0.27 events/100PY vs. 0.36 events/100PY; HR = 0.73, 95% CI = 0.25-2.08). CONCLUSIONS: Effectiveness and safety of rivaroxaban vs. warfarin are sustained in NVAF patients with co-morbid HF treated in routine practice. The general consistency between this real-world study and those from phase III randomized trial data of rivaroxaban should provide additional reassurance to clinicians regarding the use of rivaroxaban in NVAF patients with HF.

Agreement between coding schemas used to identify bleeding-related hospitalizations in claims analyses of nonvalvular atrial fibrillation patients.

BACKGROUND: Schemas to identify bleeding-related hospitalizations in claims data differ in billing codes used and coding positions allowed. We assessed agreement across bleeding-related hospitalization coding schemas for claims analyses of nonvalvular atrial fibrillation (NVAF) patients on oral anticoagulation (OAC). HYPOTHESIS: We hypothesized that prior coding schemas used to identify bleeding-related hospitalizations in claim database studies would provide varying levels of agreement in incidence rates. METHODS: Within MarketScan data, we identified adults, newly started on OAC for NVAF from January 2012 to June 2015. Billing code schemas developed by Cunningham et al., the US Food and Drug Administration (FDA) Mini-Sentinel program, and Yao et al. were used to identify bleeding-related hospitalizations as a surrogate for major bleeding. Bleeds were subcategorized as intracranial hemorrhage (ICH), gastrointestinal (GI), or other. Schema agreement was assessed by comparing incidence, rates of events/100 person-years (PYs), and Cohen's kappa statistic. RESULTS: We identified 151 738 new-users of OAC with NVAF (CHA2DS2-VASc score = 3, [interquartile range = 2-4] and median HAS-BLED score = 3 [interquartile range = 2-3]). The Cunningham, FDA Mini-Sentinel, and Yao schemas identified any bleeding-related hospitalizations in 1.87% (95% confidence interval [CI]: 1.81-1.94), 2.65% (95% CI: 2.57-2.74), and 4.66% (95% CI: 4.55-4.76) of patients (corresponding rates = 3.45, 4.90, and 8.65 events/100 PYs). Kappa agreement across schemas was weak-to-moderate (κ = 0.47-0.66) for any bleeding hospitalization. Near-perfect agreement (κ = 0.99) was observed with the FDA Mini-Sentinel and Yao schemas for ICH-related hospitalizations, but agreement was weak when comparing Cunningham to FDA Mini-Sentinel or Yao (κ = 0.52-0.53). FDA Mini-Sentinel and Yao agreement was moderate (κ = 0.62) for GI bleeding, but agreement was weak when comparing Cunningham to FDA Mini-Sentinel or Yao (κ = 0.44-0.56). For other bleeds, agreement across schemas was minimal (κ = 0.14-0.38). CONCLUSIONS: We observed varying levels of agreement among 3 bleeding-related hospitalizations schemas in NVAF patients.

Real-world costs of autosomal dominant polycystic kidney disease in the Nordics.

BACKGROUND: There is limited real-world data on the economic burden of patients with autosomal dominant polycystic kidney disease (ADPKD). The objective of this study was to estimate the annual direct and indirect costs of patients with ADPKD by severity of the disease: chronic kidney disease (CKD) stages 1-3; CKD stages 4-5; transplant recipients; and maintenance dialysis patients. METHODS: A retrospective study of ADPKD patients was undertaken April-December 2014 in Denmark, Finland, Norway and Sweden. Data on medical resource utilisation were extracted from medical charts and patients were asked to complete a self-administered questionnaire. RESULTS: A total of 266 patients were contacted, 243 (91%) of whom provided consent to participate in the study. Results showed that the economic burden of ADPKD was substantial at all levels of the disease. Lost wages due to reduced productivity were large in absolute terms across all disease strata. Mean total annual costs were highest in dialysis patients, driven by maintenance dialysis care, while the use of immunosuppressants was the main cost component for transplant care. Costs were twice as high in patients with CKD stages 4-5 compared to CKD stages 1-3. CONCLUSIONS: Costs associated with ADPKD are significant and the progression of the disease is associated with an increased frequency and intensity of medical resource utilisation. Interventions that can slow the progression of the disease have the potential to lead to substantial reductions in costs for the treatment of ADPKD.

Cross-sectional survey in CKD patients across Europe describing the association between quality of life and anaemia.

BACKGROUND: Deteriorating renal function in chronic kidney disease (CKD) patients is commonly associated with reduced haemoglobin levels, adding to the already considerable humanistic burden of CKD. This analysis evaluated the impact of anaemia on disease burden in patients with CKD stages 3-4, and in those on dialysis. METHODS: This was a descriptive, cross-sectional analysis of European data from an Adelphi CKD Disease-Specific Programme. This programme collected data from patients and their treating nephrologists/endocrinologists; patient- and physician-reported data were matched for each patient. Health-related quality of life (HRQoL) data were obtained through patient completion of the EQ-5D, SF-12 and KDQOL-36. Additional information was obtained via physician reporting of patient symptoms, and patients' reports of impaired activity. Anaemia was defined by haemoglobin level and/or current use of erythropoiesis stimulating agents. RESULTS: Significant, but modest Spearman's rank correlations were observed between haemoglobin levels and extent of HRQoL impairment, regardless of instrument used (range 0.19-0.23; all P-values < 0.0001). When stratified by anaemia status, impairment was consistently lower for anaemic than non-anaemic CKD patients across measurement scales (e.g. EQ-5D index value [standard deviation {SD}] 0.72 [0.31] vs 0.83 [0.23], respectively; P < 0.0001). Physician-reported patient tiredness was associated with increased disease burden at all levels of CKD studied (total EQ-5D index value [SD] in patients reporting no tiredness vs tiredness 0.81 [0.26] vs 0.70 [0.30] respectively; P < 0.0001) with P < 0.0001 for no tiredness vs tiredness at all stages of CKD. The presence of anaemia was associated with impaired activity levels at CKD stages 3 (37.5 % vs 28.4 %, respectively; P = 0.0044) and 4 (48.1 % vs 39.9 %, respectively; P = 0.0292), and in patients on dialysis (52.0 % vs 45.0 %, respectively; P = 0.0732). CONCLUSIONS: The analysis found that CKD patients with anaemia typically had a lower HRQoL than those without anaemia. The impairment correlated with anaemia was more apparent in non-dialysis patients with CKD stages 3 or 4 than in those receiving dialysis. Coexisting CKD and anaemia may have an impact on patient HRQoL similar to other chronic conditions such as diabetes, epilepsy or certain forms of cancer.

Clinical burden of pneumonia, meningitis and septicemia in Norway 2 years after 7-valent pneumococcal conjugate vaccine introduction.

AIMS: This population-based, retrospective study quantified the rates of all-cause and pneumococcal pneumonia, meningitis and septicemia in Norway from 2008 to 2009 and determined the proportions of cases caused by pneumococcal vaccine serotypes. METHODS: Data on patients with all-cause and pneumococcal pneumonia, meningitis and septicemia were obtained from the Norwegian Patient Registry, which collects hospitalization data from all Norwegian public hospitals based on International Classification of Diseases codes. Norwegian Patient Registry case records linked to the Norwegian Surveillance System for Communicable Diseases provided serotype data for invasive pneumococcal disease in patients with microbiological cultures. RESULTS: In 2008 and 2009, hospitalization rates were relatively stable for all-cause pneumonia (5.28 and 5.35, respectively, per 1000), meningitis (10.70 and 9.67, respectively, per 100,000), and septicemia (from 171.81 to 161.46 per 100,000). In contrast, rates decreased for International Classification of Diseases-10 diagnosed pneumococcal pneumonia (from 13.66 to 10.52 per 100,000), although these cases may be under-reported because of inclusion in all-cause pneumonia. Rates also decreased in diagnosed pneumococcal meningitis (from 1.60 to 1.19 per 100,000) and diagnosed pneumococcal septicemia (from 9.08 to 7.94 per 100,000). Diagnosed pneumococcal disease rates were highest in younger children and older adults, peaking at ⩾ 60 years old. Pneumococcal pneumonia, meningitis and septicemia caused by serotypes included in the 7-valent pneumococcal conjugate vaccine decreased substantially during the study period, with corresponding serotype replacement by non-7-valent pneumococcal conjugate vaccine serotypes. CONCLUSIONS: From 2008 to 2009, International Classification of Diseases-10 diagnosed pneumococcal pneumonia, meningitis and septicemia decreased in most age groups but remained greatest among subjects aged 0-1 and ⩾ 60 years.

MASQOT-GUI: spot quality assessment for the two-channel microarray platform.

UNLABELLED: MASQOT-GUI provides an open-source, platform-independent software pipeline for two-channel microarray spot quality control. This includes gridding, segmentation, quantification, quality assessment and data visualization. It hosts a set of independent applications, with interactions between the tools as well as import and export support for external software. The implementation of automated multivariate quality control assessment, which is a unique feature of MASQOT-GUI, is based on the previously documented and evaluated MASQOT methodology. Further abilities of the application are outlined and illustrated. AVAILABILITY: MASQOT-GUI is Java-based and licensed under the GNU LGPL. Source code and installation files are available for download at http://masqot-gui.sourceforge.net/