Cost-effectiveness analysis of branded and authorized generic celecoxib for patients with chronic pain in Japan.

OBJECTIVES: The aim of this study was to examine the cost-effectiveness of branded and authorized generic (AG) celecoxib for chronic pain patients with osteoarthritis (OA), rheumatoid arthritis (RA), and low back pain (LBP), using real-world cost information for loxoprofen and pharmacotherapy for gastrointestinal bleeding. METHODS: This cost-effectiveness analysis was performed as a long-term simulation using the Markov model from the Japanese public healthcare payer's perspective. The analysis was conducted using loxoprofen with real-world weighted price by branded/generic distribution (hereinafter, loxoprofen with weighted price) as a comparator. In the model, we simulated the prognosis of patients with chronic pain by OA, RA, and LBP treated with loxoprofen or celecoxib, over a lifetime period. RESULTS: A cost-increase of 129,688 JPY (1,245.00 USD) for branded celecoxib and a cost-reduction of 6,268 JPY (60.17 USD) for AG celecoxib were recognized per patient in lifetime horizon, compared to loxoprofen with weighted price. No case was recognized to reverse the results of cost-saving by AG celecoxib in one-way sensitivity analysis. The incremental cost-effectiveness ratio of branded celecoxib attained 5,403,667 JPY/QALY (51,875.20 USD/QALY), compared to loxoprofen with the weighted price. CONCLUSION: The current cost-effectiveness analysis for AG celecoxib revealed its good value for costs, considering the patients' future risk of gastrointestinal injury; also, the impact on costs due to AG celecoxib against loxoprofen will be small. It implies that the disadvantage of AG celecoxib being slightly more expensive than generic loxoprofen could be offset by the good cost-effectiveness during the prognosis.

Cost Effectiveness of Bosentan for Pulmonary Arterial Hypertension: A Systematic Review.

Objectives: Although many studies have reported on the cost-effectiveness of bosentan for treating pulmonary arterial hypertension (PAH), a systematic review of economic evaluations of bosentan is currently lacking. Objective evaluation of current pharmacoeconomic evidence can assist decision makers in determining the appropriate place in therapy of a new medication. Methods: Systematic literature searches were conducted in English-language databases (MEDLINE, EMBASE, EconLit databases, and the Cochrane Library) and Chinese-language databases (China National Knowledge Infrastructure, WanFang Data, and Chongqing VIP) to identify studies assessing the cost-effectiveness of bosentan for PAH treatments. Results: A total of 8 published studies were selected for inclusion. Among them were two studies comparing bosentan with epoprostenol and treprostinil. Both results indicated that bosentan was more cost-effective than epoprostenol, while the results of bosentan and treprostinil were not consistent. Four studies compared bosentan with other endothelin receptor antagonists, which indicated ambrisentan might be the drug of choice for its economic advantages and improved safety profile. Only two economic evaluations provided data to compare bosentan versus sildenafil, and the results favored the use of sildenafil in PAH patients. Four studies compared bosentan with conventional, supportive, or palliative therapy, and whether bosentan was cost-effective was uncertain. Conclusions: Bosentan may represent a more cost-effective option compared with epoprostenol and conventional or palliative therapy. There was unanimous agreement that bosentan was not a cost-effective front-line therapy compared with sildenafil and other endothelin receptor antagonists. However, high-quality cost-effectiveness analyses that utilize long-term follow-up data and have no conflicts of interest are still needed.

Weather and headache onset: a large-scale study of headache medicine purchases.

It is widely recognized that weather changes can trigger headache onset. Most people who develop headaches choose to self-medicate rather than visit a hospital or clinic. We investigated the association between weather and headache onset using large-sample sales of the headache medicine, loxoprofen. We collected daily sales figures of loxoprofen and over-the-counter drugs over a 1-year period from a drugstore chain in western Shizuoka prefecture, Japan. To adjust for changes in daily sales of loxoprofen due to social environmental factors, we calculated a proportion of loxoprofen daily sales to over-the-counter drug daily sales. At the same time, we obtained weather data for the study region from the website of the Japan Meteorological Agency. We performed linear regression analysis to ascertain the association between weather conditions and the loxoprofen daily sales proportion. We also conducted a separate questionnaire survey at the same drugstores to determine the reason why people purchased loxoprofen. Over the study period, we surveyed the sale of hundreds of thousands of loxoprofen tablets. Most people purchased loxoprofen because they had a headache. We found that the sales proportion of loxoprofen increased when average barometric pressure decreased, and that precipitation, average humidity, and minimum humidity increased on loxoprofen purchase days compared to the previous day of purchases. This study, performed using a large dataset that was easy-to-collect and representative of the general population, revealed that sales of loxoprofen, which can represent the onset and aggravation of headache, significantly increased with worsening weather conditions.

[Efficiency of initiation with ambrisentan versus bosentan in the treatment of pulmonary arterial hypertension]. / Eficiencia del inicio con ambrisentan frente a bosentan en el tratamiento de la hipertensión arterial pulmonar.

OBJECTIVE: To evaluate the efficiency of initiation with endothelin receptor antagonists, ambrisentan or bosentan, followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids in the treatment of pulmonary arterial hypertension, from the Spanish National Health System perspective. METHODS: A Markov model was developed based on the four New York Heart Association functional classes. A panel of three experts reached a consensus on patient management based on clinical practice. Patients revised their treatment every 12 weeks, based on their health status and previous medication records. Pharmacological treatment costs and costs associated with very frequent adverse events (AE) were considered in a horizon of 60 weeks. Outcomes were measured in qualityadjusted life years (QALY). A probabilistic sensitivity analysis was performed. RESULTS: No clinically relevant differences in QALY per-patient and year were found for initiation with ambrisentan and bosentan: 0.6853 and 0.6902, respectively. Initiation with ambrisentan resulted in lower pharmacological treatment and AE management costs: ?35,550 and ?117 versus ?40,224 and ?171. In the sensitivity analysis, initiation with ambrisentan resulted in a negative significant cost difference: ?-4,982; CI95%[?- 8,014; ?-2,500]; while no significant differences in QALY were found: -0.0044; CI95%[-0.0189; 0.0101]. CONCLUSIONS: Initiation with ambrisentan followed by sequential combination with phosphodiesterase-5 inhibitors and prostanoids yields comparable outcomes at lower costs than initiation with bosentan.

Objetivo: Se pretende evaluar la eficiencia del tratamiento secuencial de combinación de la hipertensión arterial pulmonar iniciado con antagonistas del receptor de la endotelina, ambrisentan o bosentan, seguido de inhibidores de la fosfodiesterasa- 5 y prostanoides, desde la perspectiva del Sistema Nacional de Salud. Métodos: Se desarrolló un modelo de Markov basado en las cuatro clases funcionales de la New York Heart Association. Un panel de tres expertos alcanzó un consenso sobre el manejo del paciente basado en la práctica clínica. Los pacientes revisaron su tratamiento cada 12 semanas, en función de su estado de salud y de la medicación recibida previamente. Se incluyeron costes farmacológicos y costes asociados al manejo de eventos adversos (EA) muy frecuentes, en un horizonte de 60 semanas. Los resultados se expresaron en términos de los años de vida ajustados por calidad (AVAC). Se realizó un análisis de sensibilidad probabilístico. Resultados: No se encontraron diferencias clínicamente relevantes en los AVAC por paciente y año para el inicio con ambrisentan y bosentan: 0,6853 y 0,6902, respectivamente. El inicio con ambrisentan resultó en un coste farmacológico y asociado al manejo de EA menor: 35.550 ??y 117 ??frente a 40.224 ??y 171 ?. En el análisis de sensibilidad, el inicio con ambrisentan presentó una diferencia de costes totales negativa y significativa: -4.982 ?; IC95%[-8.014 ?; -2.500 ?]; mientras que no se detectaron diferencias significativas en los AVAC: -0,0044; IC95%[-0,0189; 0,0101]. Conclusiones: El tratamiento secuencial de combinación de la HAP iniciado con ambrisentan, seguido de inhibidores de la fosfodiesterasa- 5 y prostanoides, proporciona resultados en salud comparables y menores costes que el tratamiento iniciado con bosentan.

Phytochemicals and antioxidant capacities in rice brans of different color.

Rice bran, a byproduct of the rice milling process, contains most of the phytochemicals. This study aimed at determining the concentrations of lipophilic, solvent-extractable (free), and cell wall-bound (bound) phytochemicals and their antioxidant capacities from brans of white, light brown, brown, purple, and red colors, and broccoli and blueberry for comparison. The concentrations of lipophilic antioxidants of vitamin E (tocopherol and tocotrienols) and γ-oryzanols were 319.67 to 443.73 and 3861.93 to 5911.12 µg/g bran dry weight (DW), respectively, and were not associated with bran color. The total phenolic, total flavonoid, and antioxidant capacities of ORAC (oxygen radical absorbance capacity), DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging, and iron-chelating in the free fraction were correlated with the intensity of bran color, while variations of these in the bound fraction were less than those in the free fraction among brans. Compounds in the bound fraction had higher antioxidant capacity of ORAC than DPPH, relative to those in the free fraction. The bound fraction of light-color brans contributed as much to its total ORAC as the free fraction. Total proanthocyanidin concentration was the highest in red rice bran, while total anthocyanin was highest in purple brans. The predominant anthocyanin was cyanidin-3-glucoside. Red and purple brans had several fold higher total phenolics and flavonoids as well as ORAC and DPPH, from both free and bound fractions, than freeze-dried blueberry and broccoli. These results indicate that rice brans are natural sources of hydrophilic and lipophilic phytochemicals for use in quality control of various food systems as well as for nutraceutical and functional food application.

Oral therapies for the treatment of pulmonary arterial hypertension: a population-based cost-minimization analysis.

BACKGROUND AND OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare but life-threatening condition that is characterized by progressive elevation of pulmonary artery pressure and pulmonary vascular resistance, leading to right-sided heart failure and frequently death. Orally administered agents used for the treatment of symptomatic, moderate-to-severe PAH include sildenafil and the endothelin (ET) receptor antagonists (ERAs), bosentan and sitaxentan (sitaxsentan). Ambrisentan is a new oral ET(A) receptor-selective ERA, with higher ET receptor affinity than bosentan. Placebo-controlled, randomized clinical trials (RCTs) have demonstrated that ambrisentan (5 or 10 mg/day) is safe and effective. To provide health economic data on the multiple oral PAH therapies currently available, a population-based cost-minimization analysis (CMA) was conducted for Canada. METHODS: The primary requirement for a CMA is that all clinical outcomes be equivalent between comparator treatments. To provide such supporting data, a literature search was conducted for RCTs of oral agents used to treat symptomatic PAH. This was followed by application of direct and indirect statistical methods to support the hypothesis of clinical equivalence between the oral agents. Estimates for PAH prevalence, incidence and death rates were then used to build a population-based CMA model. The base-case analysis considered costs for drug therapy, outpatient pharmacy costs, medical consultations and visits, laboratory and diagnostic procedures and other healthcare-related resources. In addition, costs for secondary pharmacotherapy in cases where the primary agent had to be discontinued because of adverse effects were also included. The time horizon for evaluating pharmacotherapy was 3 years, all costs were in 2008 Canadian dollars ($Can) and the costs were discounted at a rate of 3% annually. The study perspective was the Canadian healthcare system. RESULTS: There were no double-blind RCTs comparing ambrisentan with any of the other oral agents. Therefore, an indirect comparison of placebo-controlled trials of PAH drugs had to be used to support the clinical equivalence. This included a calculation of standardized mean differences (SMD) between agents (vs placebo) and a meta-regression analysis on the primary and secondary trial endpoints. Keeping in mind the caveats associated with indirect trial comparisons, the data suggested similar clinical efficacy over 12-16 weeks between agents, as indicated by the identical magnitude of the SMD between the active agent and placebo and the non-significant differences between drugs as determined by the meta-regression analysis. The population-based model projected that the number of PAH patients clinically suitable for these drugs in Canada would be 931 in the first full-budget year (i.e. 2009) with an increase to 1114 by the third full year. The CMA revealed the following rank order of the least to most costly agent; sildenafil, ambrisentan, sitaxentan and bosentan. Sildenafil was the least costly, primarily because of the lower daily drug-acquisition cost. Of the three ERAs, ambrisentan would be associated with annual cost savings of $Can3.4 and $Can5.6 million when used as an alternative to sitaxentan or bosentan, respectively. CONCLUSIONS: Ambrisentan is less costly than other available ERAs, including bosentan and sitaxentan, but is more costly than sildenafil. In PAH patients in whom an ERA is the preferred agent, ambrisentan may be the drug of choice because of its economic advantages and improved safety profile.

Role of ambrisentan in the management of pulmonary hypertension.

OBJECTIVE: To review the role of ambrisentan in the treatment of pulmonary arterial hypertension (PAH). DATA SOURCES: Literature was accessed through MEDLINE (1950-June 2008), Iowa Drug Information Service (1966-March 2008), EMBASE (1966-June 2008), bibliographies of pertinent articles, and unpublished data provided by the manufacturer and the Food and Drug Administration (FDA). Search terms included ambrisentan, endothelin antagonist, pulmonary hypertension, and pulmonary arterial hypertension. Due to limited literature available, additional criteria to limit searches were not used. STUDY SELECTION AND DATA EXTRACTION: Abstracts and original preclinical and clinical research reports available in the English language were identified for review. All manufacturer-provided data were also evaluated. Literature related to ambrisentan, endothelin antagonists, pulmonary hypertension, and pulmonary arterial hypertension were included. Four clinical trials evaluated the efficacy of ambrisentan in adults with symptomatic PAH. DATA SYNTHESIS: Ambrisentan is the latest endothelin-receptor antagonist (ERA) to obtain FDA approval for the treatment of PAH. It joins the first FDA-approved ERA, bosentan. Like bosentan, ambrisentan is available orally (with once-daily dosing compared with bosentan's twice-daily dosing) and has been shown to improve exercise capacity and delay clinical worsening. As with bosentan, the most significant safety concerns with ambrisentan relate to potential liver injury and a contraindication in pregnancy. Although ambrisentan has higher affinity for the endothelin type A receptor than for the endothelin type B receptor, specific advantages of this selectivity, in terms of efficacy compared with bosentan, a nonselective agent, have not been demonstrated. CONCLUSIONS: Ambrisentan has been shown to be an effective ERA in patients with PAH. A significant advantage of ambrisentan is the lack of any clinically important drug interactions with warfarin and sildenafil, which are frequently used by patients being treated for PAH.

Ambrisentan for the management of pulmonary arterial hypertension.

BACKGROUND: Approved by the US Food and Drug Administration in 2007, ambrisentan is the second oral endothelin A-receptor antagonist available for the management of pulmonary arterial hypertension (PAH) in patients with World Health Organization class II or III symptoms. OBJECTIVE: This article examines the clinical pharmacology of ambrisentan, its efficacy and adverse effects, and future directions for research. METHODS: Pertinent articles and abstracts were identified through searches of MEDLINE and Current Contents from 1966 to January 15, 2008, using the term ambrisentan. The reference lists of identified articles were searched for additional publications. Abstracts presented at professional meetings from 2005 through 2007 were also reviewed. RESULTS: The literature review identified 3 studies of ambrisentan in PAH: 1 dose-ranging study; 2 randomized, double-blind, placebo-controlled studies; and 1 drug-conversion study. In the dose-ranging study, ambrisentan at doses of 1 to 10 mg was associated with significant improvements from baseline in the 6-minute walk distance at 12 weeks that ranged from 33.9 m with ambrisentan 1 mg (P = 0.003) to 38.1 m with ambrisentan 5 mg (P = 0.001). In the placebo-controlled studies, ambrisentan at doses of 2.5 to 10 mg/d was associated with significant improvements versus placebo in the 6-minute walk distance at 12 weeks that ranged from 22 m with ambrisentan 2.5 mg (P = 0.022) to 59 m with ambrisentan 5 mg (P