RESUMEN
BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is used in the Japanese National Immunization Program for older adults and adults with increased risk for pneumococcal disease, however, disease incidence and associated burden remain high. We evaluated the cost-effectiveness of pneumococcal conjugate vaccines (PCVs) for adults aged 65 years and high-risk adults aged 60-64 years in Japan. RESEARCH DESIGN AND METHODS: Using a Markov model, we evaluated lifetime costs using societal and healthcare payer perspectives and estimated quality-adjusted life-years (QALYs), and number of prevented cases and deaths caused by invasive pneumococcal disease (IPD) and non-IPD. The base case analysis used a societal perspective. RESULTS: In comparison with PPSV23, the 20-valent PCV (PCV20) prevented 127 IPD cases 10,813 non-IPD cases (inpatients: 2,461, outpatients: 8,352) and 226 deaths, and gained more QALYs (+0.0015 per person) with less cost (-JPY22,513 per person). All sensitivity and scenario analyses including a payer perspective analysis indicated that the incremental cost-effectiveness ratios (ICERs) were below the cost-effectiveness threshold value in Japan (JPY5 million/QALY). CONCLUSIONS: PCV20 is both cost saving and more effective than PPSV23 for adults aged 65 years and high-risk adults aged 60-64 years in Japan.
Asunto(s)
Infecciones Neumocócicas , Vacunas Neumococicas , Años de Vida Ajustados por Calidad de Vida , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Costo-Efectividad , Japón/epidemiología , Cadenas de Markov , Infecciones Neumocócicas/prevención & control , Infecciones Neumocócicas/economía , Infecciones Neumocócicas/epidemiología , Vacunas Neumococicas/economía , Vacunas Neumococicas/administración & dosificación , Vacunas Conjugadas/economía , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/inmunologíaRESUMEN
BACKGROUND: The Japanese National Immunization Program currently includes the pediatric 13 valent pneumococcal conjugate vaccine (PCV13) to prevent pneumococcal infections. We aimed to evaluate the cost-effectiveness of 20-valent PCV (PCV20) as a pediatric vaccine versus PCV13. METHODS: A decision-analytic Markov model was used to estimate expected costs, quality-adjusted life-years (QALYs), and prevented cases and deaths caused by invasive pneumococcal disease, pneumonia, and acute otitis media over a ten-year time horizon from the societal and healthcare payer perspectives. RESULTS: PCV20 was dominant, i.e. less costly and more effective, over PCV13 (gained 294,599 QALYs and reduced Japanese yen [JPY] 352.6 billion [2.6 billion United States dollars, USD] from the societal perspective and JPY 178.9 billion [USD 1.4 billion] from the payer perspective). Sensitivity and scenario analyses validated the robustness of the base scenario results. When comparing PCV20 with PCV13, the threshold analysis revealed an incremental cost-effectiveness ratio that was within the threshold value (JPY 5 million/QALY) at a maximum acquisition cost of JPY 74,033 [USD 563] (societal perspective) and JPY 67,758 [USD 515] (payer perspective). CONCLUSIONS: As a pediatric vaccine, PCV20 was dominant over PCV13 regardless of the study perspective.
Asunto(s)
Análisis de Costo-Efectividad , Infecciones Neumocócicas , Vacunas Neumococicas , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Programas de Inmunización/economía , Japón/epidemiología , Cadenas de Markov , Otitis Media/prevención & control , Otitis Media/economía , Infecciones Neumocócicas/prevención & control , Infecciones Neumocócicas/economía , Vacunas Neumococicas/economía , Vacunas Neumococicas/administración & dosificación , Años de Vida Ajustados por Calidad de Vida , Vacunas Conjugadas/administración & dosificación , Vacunas Conjugadas/economíaRESUMEN
Background: The Global initiative for chronic Obstructive Lung Disease strategy document for COPD recommends treatment changes according to the persistence of symptoms or exacerbations. This study assessed the feasibility and outcomes of a structured step-up/step-down treatment approach in a randomized controlled clinical trial setting. Methods: Japanese patients with moderate-to-severe COPD were randomized to blinded, double-dummy treatment with twice-daily fluticasone propionate/salmeterol (FP/SAL) 250/50 µg or once-daily tiotropium bromide (TIO) 18 µg for 24 weeks (dual bronchodilator was not available). At 4-weekly intervals, patients remaining symptomatic (COPD Assessment Test score >10) or experiencing an exacerbation were offered the option to use triple therapy. Primary endpoint was the proportion of patients remaining on randomized therapy. Results: In total, 406 patients participated (mean FEV1 59%±13% predicted; COPD Assessment Test 12±6). Of these, 204 and 201 patients were included in the FP/SAL and TIO groups, respectively, of whom 67% and 63% continued treatment throughout the study; this difference was not statistically significant. Time to first therapy switch was longer with FP/SAL, but not significantly (P=0.21). More patients in Global initiative for chronic Obstructive Lung Disease (2011 criteria) groups C/D switched (FP/SAL 55%, TIO 63%) than in groups A/B (FP/SAL 27%, TIO 27%). Conclusion: Given the choice, patients with more symptoms or those experiencing an exacerbation will agree to step-up therapy. Effectiveness of disease management pathways can be tested using double-blind studies.
Asunto(s)
Broncodilatadores/uso terapéutico , Fluticasona/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Xinafoato de Salmeterol/uso terapéutico , Bromuro de Tiotropio/uso terapéutico , Administración por Inhalación , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Método Doble Ciego , Quimioterapia Combinada , Estudios de Factibilidad , Femenino , Volumen Espiratorio Forzado , Humanos , Japón , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
PURPOSE: To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC). PATIENTS AND METHODS: This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation. RESULTS: In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α). CONCLUSION: This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation.
Asunto(s)
Biomarcadores/metabolismo , Inflamación , Leucocitos Mononucleares , Neutrófilos , Enfermedad Pulmonar Obstructiva Crónica , Fumar , Esputo , Anciano , Células Cultivadas , Femenino , Humanos , Inflamación/sangre , Inflamación/patología , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Recuento de Leucocitos , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Fumar/sangre , Fumar/patología , Fumar/fisiopatología , Esputo/citología , Esputo/metabolismo , Estadística como Asunto , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
PURPOSE: Triple therapy using salmeterol/fluticasone propionate (FP) and tiotropium bromide is commonly used to treat chronic obstructive pulmonary disease (COPD), but sparse efficacy data exist in COPD patients with fewer symptoms and with a lower dose of inhaled corticosteroid in Japanese patients. The effects of of salmeterol/fluticasone propionate 50/250 µg (SFC250) twice daily plus tiotropium 18 µg (TIO) once daily and individual treatments on lung function were compared. PATIENTS AND METHODS: Fifty three Japanese COPD patients participated in this randomized, double-blind, double-dummy, Williams square design crossover study. Lung function was assessed by plethysmography and spirometry. RESULTS: The primary endpoint of postdose specific airway conductance area under the curve (AUC0-4h) on day 28 was significantly higher following SFC250 + TIO (0.854) compared with TIO (0.737, 15.8%) and SFC250 (0.663, 28.8%) alone. SFC250 + TIO significantly improved trough forced expiratory volume in 1 second from baseline versus TIO (0.161 L, P<0.001) and SFC250 (0.103 L, P=0.008). SFC250 + TIO significantly improved residual volume compared with TIO (P<0.001) and SFC250 (P=0.003) on day 28. Nonsignificant improvements were seen in trough inspiratory capacity, total lung capacity, and thoracic gas volume. There was no mean change seen in rescue medication. CONCLUSION: Triple therapy using SFC250 + TIO was well tolerated and gave a greater improvement in bronchodilation compared with TIO and SFC250 alone in Japanese patients with COPD. There was improvement in few symptoms, but no mean change was seen in patient-reported outcomes measured by rescue medication use.
Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Broncodilatadores/administración & dosificación , Antagonistas Colinérgicos/administración & dosificación , Combinación Fluticasona-Salmeterol/administración & dosificación , Pulmón/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Bromuro de Tiotropio/administración & dosificación , Administración por Inhalación , Agonistas de Receptores Adrenérgicos beta 2/efectos adversos , Anciano , Área Bajo la Curva , Broncodilatadores/efectos adversos , Antagonistas Colinérgicos/efectos adversos , Estudios Cruzados , Método Doble Ciego , Esquema de Medicación , Femenino , Combinación Fluticasona-Salmeterol/efectos adversos , Volumen Espiratorio Forzado , Humanos , Japón , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Nebulizadores y Vaporizadores , Pletismografía , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Curva ROC , Recuperación de la Función , Índice de Severidad de la Enfermedad , Espirometría , Factores de Tiempo , Bromuro de Tiotropio/efectos adversos , Resultado del Tratamiento , Capacidad VitalRESUMEN
PURPOSE: To assess the importance of inflammation in chronic obstructive pulmonary disease (COPD) by measuring airway and systemic inflammatory biomarkers in Japanese patients with the disease and relevant control groups. PATIENTS AND METHODS: This was the first study of its type in Japanese COPD patients. It was a non-treatment study in which 100 participants were enrolled into one of three groups: nonsmoking controls, current or ex-smoking controls, and COPD patients. All participants underwent standard lung function assessments and provided sputum and blood samples from which the numbers of inflammatory cells and concentrations of biomarkers were measured, using standard procedures. RESULTS: The overall trends observed in levels of inflammatory cells and biomarkers in sputum and blood in COPD were consistent with previous reports in Western studies. Increasing levels of neutrophils, interleukin 8 (IL-8), surfactant protein D (SP-D), and Krebs von den Lungen 6 (KL-6) in sputum and clara cell 16 (CC-16), high-sensitivity C-reactive protein (hs-CRP), and KL-6 in serum and plasma fibrinogen were seen in the Japanese COPD patients compared with the non-COPD control participants. In sputum, significant correlations were seen between total cell count and matrix metalloproteinase 9 (MMP-9; P<0.001), neutrophils and MMP-9 (P<0.001), macrophages and KL-6 (P<0.01), total cell count and IL-8 (P<0.05), neutrophils and IL-8 (P<0.05), and macrophages and MMP-9 (P<0.05). Significant correlations were also observed between some inflammatory cells in sputum and biomarkers in serum, with the most significant between serum CC-16 and both total cell count (P<0.005) and neutrophils (P<0.005) in sputum. CONCLUSION: These results provide evidence for the first time that COPD in Japanese patients is a multicomponent disease, involving both airway and systemic inflammation, in addition to airway obstruction. Therefore, intervention with anti-inflammatory therapy may provide additional benefit in disease management of COPD in Japan.