RESUMEN
BACKGROUND: Rituximab was approved in 1997 and is regularly one of the largest drug expenditures for Medicare; however, its benefits and costs have not been estimated from a population perspective. OBJECTIVES: To estimate both the clinical and the economic outcomes of rituximab for its approved hematological uses at the population level. RESEARCH DESIGN: Analyses using cancer registry incidence data from the Surveillance, Epidemiology, and End Results (SEER) program, and outcomes data from SEER data linked with Medicare administrative claims (SEER-Medicare data). These results were incorporated into an epidemiological simulation model of the population over time. SUBJECTS: We modeled all United States patients from 1998 to 2013 diagnosed with diffuse large B-cell lymphoma, follicular lymphoma, or chronic lymphocytic leukemia. MEASURES: Using this model, we estimated the life-years saved, as well as their economic benefit, in the United States population. We also estimated the incremental cost of adding rituximab to chemotherapy. All economic inputs were based on Medicare reimbursed amounts inflated to 2013 dollars. RESULTS: There were 279,704 cumulative life-years saved which were valued at $25.44 billion. The incremental direct medical cost of rituximab was estimated to be $8.92 billion, resulting in an incremental economic gain of $16.52 billion. CONCLUSIONS: These analyses, based on real-world evidence, show that the introduction of rituximab into clinical practice has produced a substantial number of incremental life-years. Importantly, the economic benefit of the life-years gained greatly exceeds the added costs of treatment.
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Antineoplásicos/economía , Análisis Costo-Beneficio , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma de Células B/tratamiento farmacológico , Linfoma Folicular/tratamiento farmacológico , Rituximab/economía , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Costos de los Medicamentos , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Linfoma de Células B/mortalidad , Linfoma Folicular/mortalidad , Masculino , Medicare/estadística & datos numéricos , Persona de Mediana Edad , Modelos Económicos , Método de Montecarlo , Rituximab/uso terapéutico , Programa de VERF/estadística & datos numéricos , Análisis de Supervivencia , Factores de Tiempo , Estados UnidosRESUMEN
OBJECTIVES: The primary objective of the Monotherapy Assessment of Ranolazine In Stable Angina (MARISA) trial was to determine the dose-response relationship of ranolazine, a potentially new anti-anginal compound, on symptom-limited exercise duration. BACKGROUND: Fatty acids rise precipitously in response to stress, including acute myocardial ischemia. Ranolazine is believed to partially inhibit fatty acid oxidation, shift metabolism toward carbohydrate oxidation, and increase the efficiency of oxygen use. METHODS: Patients (n = 191) with angina-limited exercise discontinued anti-anginal medications and were randomized into a double-blind four-period crossover study of sustained-release ranolazine 500, 1,000, or 1,500 mg, or placebo, each administered twice daily for one week. Exercise testing was performed at the end of each treatment during both trough and peak ranolazine plasma concentrations. RESULTS: Exercise duration at trough increased with ranolazine 500, 1,000, and 1,500 mg twice daily by 94, 103, and 116 s, respectively, all greater (p < 0.005) than the 70-s increase on placebo. Dose-related increases in exercise duration at peak and in times to 1 mm ST-segment depression at trough and peak and to angina at trough and peak were also demonstrated (all p < 0.005). Ranolazine had negligible effects on heart rate and blood pressure. One year survival rate combining data from the MARISA trial and its open-label follow-on study was 96.3 +/- 1.7%. CONCLUSIONS: In chronic angina patients, ranolazine monotherapy was well tolerated and increased exercise performance throughout its dosing interval at all doses studied without clinically meaningful hemodynamic effects. One-year survival was not lower than expected in this high-risk patient population. This metabolic approach to treating myocardial ischemia may offer a new therapeutic option for chronic angina patients.
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Angina de Pecho/tratamiento farmacológico , Angina de Pecho/mortalidad , Inhibidores Enzimáticos/uso terapéutico , Piperazinas/uso terapéutico , Acetanilidas , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Inhibidores Enzimáticos/administración & dosificación , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Ranolazina , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
CONTEXT: Many patients with chronic angina experience anginal episodes despite revascularization and antianginal medications. In a previous trial, antianginal monotherapy with ranolazine, a drug believed to partially inhibit fatty acid oxidation, increased treadmill exercise performance; however, its long-term efficacy and safety have not been studied in combination with beta-blockers or calcium antagonists in a large patient population with severe chronic angina. OBJECTIVES: To determine whether, at trough levels, ranolazine improves the total exercise time of patients who have symptoms of chronic angina and who experience angina and ischemia at low workloads despite taking standard doses of atenolol, amlodipine, or diltiazem and to determine times to angina onset and to electrocardiographic evidence of myocardial ischemia, effect on angina attacks and nitroglycerin use, and effect on long-term survival in an open-label observational study extension. DESIGN, SETTING, AND PATIENTS: A randomized, 3-group parallel, double-blind, placebo-controlled trial of 823 eligible adults with symptomatic chronic angina who were randomly assigned to receive placebo or 1 of 2 doses of ranolazine. Patients treated at the 118 participating ambulatory outpatient settings in several countries were enrolled in the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial from July 1999 to August 2001 and followed up through October 31, 2002. INTERVENTION: Patients received twice-daily placebo or 750 mg or 1000 mg of ranolazine. Treadmill exercise 12 hours (trough) and 4 hours (peak) after dosing was assessed after 2, 6 (trough only), and 12 weeks of treatment. MAIN OUTCOME MEASURES: Change in exercise duration, time to onset of angina, time to onset of ischemia, nitroglycerin use, and number of angina attacks. RESULTS: Trough exercise duration increased by 115.6 seconds from baseline in both ranolazine groups (pooled) vs 91.7 seconds in the placebo group (P =.01). The times to angina and to electrocardiographic ischemia also increased in the ranolazine groups, at peak more than at trough. The increases did not depend on changes in blood pressure, heart rate, or background antianginal therapy and persisted throughout 12 weeks. Ranolazine reduced angina attacks and nitroglycerin use by about 1 per week vs placebo (P<.02). Survival of 750 patients taking ranolazine during the CARISA trial or its associated long-term open-label study was 98.4% in the first year and 95.9% in the second year. CONCLUSION: Twice-daily doses of ranolazine increased exercise capacity and provided additional antianginal relief to symptomatic patients with severe chronic angina taking standard doses of atenolol, amlodipine, or diltiazem, without evident adverse, long-term survival consequences over 1 to 2 years of therapy.