Treatment patterns, resource use and costs of idiopathic pulmonary fibrosis in Spain--results of a Delphi Panel.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a form of chronic fibrosing interstitial pneumonia characterized by progressive worsening of dyspnea and lung function, with a poor prognosis. The objective of this study was to determine treatment patterns, resource use and costs of managing Spanish patients with IPF. METHODS: A three-round Delphi consensus panel of 15 clinical experts was held between December 2012 and June 2013 using questionnaires to describe the management of patients with IPF. A cost analysis based on Delphi panel estimates was made from the Spanish National Health System (NHS) perspective, including the direct costs of IPF diagnosis and management. Unit costs were applied to Delphi panel estimates of health resource use. Univariate sensitivity analyses were made to evaluate uncertainties in parameters. RESULTS: The Delphi panel estimated that 20, 60 and 20% of IPF patients presented with stable disease, slow and rapid disease progression, respectively. The estimated annual cost per patient with stable disease, slow and rapid disease progression was €11,484, €20,978 and €57,759, respectively. This corresponds to a weighted average annual cost of €26,435 with itemized costs of €1,184 (4.5), €7,147 (27.0), €5,950 (22.5), €11,666 (44.1) and €488 (1.9%) for the diagnosis of IPF, treatment, monitoring, management of acute exacerbations and end-of-life care, respectively. The parameter that varied the annual cost per patient the most was resource use associated with acute exacerbations. CONCLUSIONS: The management of patients with IPF in Spain, especially patients with rapid disease progression, has a high economic impact on the NHS.

Digestive Enzyme Activities in Mussel Mytilus californianus Endure Acute Heat Exposure in Air.

The mussel Mytilus californianus is an ecosystem engineer forming beds along the coastlines of Northeastern Pacific shores. As sessile organisms, they modulate their energy balance through valve movements, feeding, and digestive functionality. A recent study observed that activity of the digestive enzyme cellulase was higher than predicted in mussels high on the shore, where temperatures are characteristically high and food availability is limited compared to low-shore habitats. In the current study, we predicted that this scavenging behavior is induced to mitigate energy losses related to heat-shock responses-that cellulase and amylase will display hyperactivity for limited recourses in the face of aerial heating. In the laboratory, we acclimated mussels to three complex diets that differed in starch and cellulose composition, followed by two acute heat shocks (+8°C) in the laboratory. Results showed no hyperactivity of amylase and cellulase in heated mussels. These results differ from previous studies that showed lowered amylase activity following heat acclimation. This difference in amylase activity across heat-stress exposure time is important when analyzing mussel bed disturbances following heat waves that compromise energy balance or cause death within adult populations.

A cost-effectiveness analysis of patiromer for the treatment of hyperkalemia in chronic kidney disease patients with and without heart failure in Spain.

AIMS: Renin-angiotensin-aldosterone system inhibitors (RAASi) therapy is commonly used to reduce the risk of death and to slow down disease progression in patients with chronic kidney disease (CKD), heart failure (HF) and hypertension. However, the cardio-renal benefits of RAASi therapy are also associated with an increased risk of hyperkalemia (HK), which may lead to dose reduction or discontinuation of therapy. Patiromer has demonstrated to reduce the risk of HK, which enables to maintain optimal doses of RAASi therapy. This study aimed to assess the cost-effectiveness of patiromer for the management of HK in CKD patients with and without HF in Spain. METHODS: A Markov model was developed to evaluate the costs and benefits of patiromer for the management of HK in patients with CKD stages 3-4 with and without HF treated with RAASi over a lifetime horizon. The main outcomes included total direct costs (€2021), quality-adjusted life-years (QALYs), life-years gained (LYG) and incremental cost-effectiveness ratio (ICER). Deterministic one-way and probabilistic sensitivity analyses were performed to assess the robustness of the results. RESULTS: Patiromer was more effective compared to no patiromer (5.76 vs 5.57 QALYs; 7.73 vs 7.50 LYG), and resulted in an incremental cost of €3,574, yielding an ICER of €19,092/QALY gained and of €15,236/LYG. Sensitivity analyses suggested that the results were robust to changes in most input parameters. CONCLUSIONS: Patiromer is a cost-effective intervention in maintaining normokalemia and enabling optimal RAASi therapy in patients with CKD stages 3-4 with and without HF in Spain.

Economic Impact of Low Adherence to COPD Management Guidelines in Spain.

OBJECTIVE: The objective of this study was to assess the non-adherence level of Spanish clinical practice to guideline recommendations for the treatment of chronic obstructive pulmonary disease (COPD) and to estimate the potential impact on pharmaceutical expenditure resulting from transitioning current treatment patterns according to guidelines. METHODS: A model was developed to compare current prescribing patterns with two alternative scenarios: the first aligned with the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2020) recommendations, and the second with the Spanish Guidelines for COPD (GesEPOC 2017). Current treatment practice was obtained from publications that describe treatment patterns by pulmonology departments in Spain. The economic impact between patterns was calculated from the perspective of the Spanish National Health System (NHS), considering the annual pharmacological costs of COPD inhaled maintenance therapy. Two additional analyses were performed: one that included current prescribing patterns of patients managed by pulmonology and primary care centers in Spain (published aggregated data); and another that only considered the appropriate use of inhaled corticosteroids (ICS) treatment according to guidelines. RESULTS: It was estimated that 54% and 38% of patients were not treated in line with GOLD and GesEPOC recommendations, respectively, mainly due to a broader use of ICS-based therapies. Adapting treatment to recommendations could provide a potential annual cost-saving of €17,792,022 (according to GOLD) and €5,881,785 (according to GesEPOC). In scenario analysis 1, a 26% of non-adherence to GesEPOC guideline was observed with a potential annual pharmacological cost-saving of €2,707,554. In scenario analysis 2, considering only inappropriate use of ICS treatment, an annual cost-saving of €17,863,750 (according to GOLD) and €9,904,409 (according to GesEPOC) was calculated. CONCLUSION: More than a third of treatments for COPD patients in Spain are not prescribed in accordance with guideline recommendations. The adaptation of clinical practice to guideline recommendations could provide important cost-savings for the Spanish NHS.

[Cost-reduction analysis for oral versus intravenous fludarabine (Beneflur) in Spain]. / Análisis de minimización de costes de fludarabina (Beneflur) oral vs. vía intravenosa en España.

INTRODUCTION: Various international studies have shown that fludarabine is effective, safe, and efficient for treating B-cell chronic lymphocytic leukemia (B-CLL). The purpose of the present study was to carry out a cost-minimization analysis for two alternative forms of fludarabine (oral and intravenous) used to treat B-CLL in Spain. METHODS: The presence of clinical evidence about the treatment equivalence of the two options being compared (oral fludarabine vs. intravenous fludarabine) led us to carry out a cost-minimization analysis. A pharmacoeconomic model was constructed to compile data from the literature and experts' opinions in order to determine the use of health resources associated with the treatment; unit costs were obtained from Spanish databases. The analysis contemplated two perspectives: that of the national health service, which includes only direct health costs, and the social perspective, which also includes the indirect costs that result from loss of productivity. RESULTS: Although fludarabine in its oral form has a higher purchase price than generic intravenous fludarabine does, increased administration costs for the latter, which is used in hospitals, mean that oral fludarabine use produces total savings of euro1,908 and euro1,292 for single-drug therapy and combined therapy with cyclophosphamide, respectively. Including indirect costs increased the savings associated with the oral form of the drug. CONCLUSIONS: In B-CLL patients, treatment with oral fludarabine has a lower cost than treatment with intravenous fludarabine, in both single-drug therapy and combined therapy. Various sensitivity analyses confirmed these results and showed that oral fludarabine should be the treatment of choice for B-CLL in Spain, unless contrain.

Role of 5-lipoxygenase pathway in the regulation of RAW 264.7 macrophage proliferation.

Arachidonic acid (AA) metabolites control cell proliferation, among other physiologic functions. RAW 264.7 macrophages can metabolise AA through the cyclooxygenase and lipoxygenase (LOX) pathways. We aimed to study the role of AA-metabolites derived from 5-LOX in the control of RAW 264.7 macrophage growth. Our results show that zileuton, a specific 5-LOX inhibitor, and nordihydroguaiaretic acid (NDGA), a non-specific LOX inhibitor, inhibit cell proliferation and [(3)H]-thymidine incorporation in a concentration-dependent fashion. Growth inhibition induced by NDGA can be explained by an apoptotic process, while zileuton does not seem to induce apoptosis. Moreover, these treatments delay the cell cycle, as analysed by flow cytometry. On the other hand, the leukotriene (LT) B(4) receptor antagonist U-75302, the LTD(4) receptor antagonists LY-171883 and MK-571, and the cysteinyl-LT receptor antagonist REV-5901 also inhibit cell proliferation and [(3)H]-thymidine incorporation in a concentration-dependent manner, and delay the RAW 264.7 cell cycle. However, these antagonists did not induce annexin V staining, caspase activation or DNA fragmentation. Furthermore, we demonstrated that exogenous addition of LTB(4) or LTD(4) revert the cell growth inhibition induced by zileuton or the leukotriene receptor antagonists mentioned above. Finally, we observed that LTB(4) and LTD(4), in the absence of growth factors, have pro-proliferative effects on macrophages, and we obtained preliminary evidences that this effect could be through mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. In conclusion, our results show that the interaction between LTB(4) and LTD(4) with its respective receptor is involved in the control of RAW 264.7 macrophage growth.

Cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% in the treatment of actinic keratosis in Spain.

OBJECTIVE: The aim of this study is to conduct a cost-effectiveness analysis of 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain. METHODS: An analytical decision-making model was constructed to compare whether 5-FU/SA was a cost-effective option compared with cryotherapy from the perspective of the Spanish National Health System with a time horizon of 6 months. Costs were expressed in 2014 euros. RESULTS: The cost of patients with hyperkeratotic actinic keratosis treated with 5-FU/SA or cryotherapy was €266 and €285, respectively. 5-FU/SA was associated with higher rates of treatment success and, consequently, more quality-adjusted life years, than cryotherapy. Therefore, 5-FU/SA was the dominant treatment, as it was associated with a lower treatment cost and greater effectiveness than cryotherapy. CONCLUSIONS: Economically, 5-FU/SA was a dominant option compared with cryotherapy in the treatment of isolated hyperkeratotic actinic keratosis lesions in Spain.

Treatment patterns, use of resources, and costs of advanced non-small-cell lung cancer patients in Spain: results from a Delphi panel.

INTRODUCTION: Approximately 80-85% of lung cancer patients are diagnosed with non-small-cell lung cancer (NSCLC), of which 50% of patients present with advanced or metastatic disease. The objective of this study was to describe treatment patterns, use of resources and costs associated with treating advanced or metastatic NSCLC patients in Spain. METHODS: A two-round Delphi consensus panel of clinical experts was carried out to describe local clinical patterns based on treatment algorithms from SEOM and ASCO treatment guidelines. The panel consisted of 19 oncologists and 1 hospital pharmacist, who were asked during the first round to define therapeutic pathways for NSCLC by the patients' performance status, age and histology; to quantify the use of resources associated with the preparation and administration of anticancer pharmacotherapy; management of adverse events associated with anticancer pharmacotherapy; and best supportive care (BSC). The second round was used to try to reduce the variability of responses in some questions and to further describe differences between intravenous and oral therapy. 2009 unit costs were applied to the use of resources described by the clinical experts. The perspective of the study was from the Spanish National Healthcare System. RESULTS: Performance status guided therapy decision and led to differences in costs. Patients with a performance status of 0-2 were expected to receive anticancer pharmacotherapy while patients with a performance status of 3-4 received BSC including analgesics and corticosteroids. Anticancer pharmacotherapies containing cisplatin or carboplatin were used preferably in first-line treatment, while the usual second- and third-line treatments were docetaxel, erlotinib or pemetrexed monotherapy. The importance of the cost of anticancer pharmacotherapy as a proportion of total healthcare costs was higher for combination therapies containing bevacizumab or pemetrexed. The anticancer pharmacotherapies associated with adverse events like febrile neutropenia or infection increased the total treatment cost. Administration costs were more relevant in regimens containing cisplatin and were low for orally administered therapies. The total cost per patient with advanced or metastatic NSCLC from starting anticancer therapy until death was estimated to be between €11,301 and €32,754 depending on the number of treatment lines received. CONCLUSIONS: In the treatment of advanced or metastatic NSCLC, healthcare costs are impacted by line of treatment, patient performance status, type of administration of therapy and adverse event management.

[Economic evaluation of tramadol/paracetamol in the management of pain in patients with osteoarthritis in Spain]. / Evaluación económica de tramadol/paracetamol en el manejo del dolor en pacientes con osteoartrosis en España.

OBJECTIVE: To compare the costs of treating osteoarthritis (OA) pain using combination tramadol/paracetamol tablets, Non-Steroidal Anti-Inflammatory Agents (NSAID) alone or NSAID plus proton pump inhibitors (PPI) from the perspective of the Spanish National Health System. METHODS: A decision-analytical model was constructed to analyze the cost associated with three treatment strategies over 6 months. A cost-minimization approach was used, which considered data related to resource use, medication costs and costs for the treatment of adverse events. RESULTS: In the base-case analysis, costs for 6 months of treatment of OA pain using tramadol/paracetamol were €232.86, compared with €274.60 for NSAID + PPI and €133.75 for NSAID alone. This provided a savings of €41.74 per patient over 6 months for tramadol/paracetamol compared with NSAID + PPI and a cost increase of €99.11 compared with NSAID alone. When renal adverse events associated with NSAID were considered, tramadol/paracetamol was cost saving compared with all NSAID-based regimens (saving €140.02 vs NSAID alone, €280.86 vs NSAID + PPI). CONCLUSION: Based on the results of a theoretical decision-analytic model, the data obtained may suggest that tramadol/paracetamol is cost saving compared with NSAID + PPI for the treatment of OA pain over a period of 6 months. Tramadol/paracetamol is also cost saving compared with treatment with NSAID alone if considering renal adverse events.

Enantioselective effect of 12(S)-hydroxyeicosatetraenoic acid on 3T6 fibroblast growth through ERK 1/2 and p38 MAPK pathways and cyclin D1 activation.

Hydroxyeicosatetraenoic acids (HETEs) have numerous physiological effects, including modulation of cell proliferation and differentiation. However, little is known about the selective effects of HETE enantiomers on cell proliferation and cell signalling pathways involved in the regulation of cell growth. Furthermore, information on epithelial and endothelial cells growth is controversial. Recently, we demonstrated that 5-, 12-, and 15-HETE are involved in the control of 3T6 fibroblast growth though serine/treonine Akt/PKB (Akt) pathway. Here we examined the participation of both enantiomers (S and R) of HETEs in the control of 3T6 fibroblast growth. Our results show that HETEs (5-, 12-, and 15-HETE) are enantioselective on protein and DNA synthesis and 3T6 fibroblast growth. Furthermore, we observed that 12(S)-HETE induces the enhancement of cAMP and intracellular calcium concentration, whereas 12(R)-HETE was uneffective. Our findings also demonstrated that 12(S)-HETE exerts these effects through enantiospecific interactions with a cellular element, probably a plasma membrane receptor coupling to a pertussis toxin-sensitive protein G. Moreover, these elements may be involved in the activation of mitogen-activated protein kinase pathways which induce the enhancement of cyclin D(1) levels.

Epoxyeicosatrienoic acids induce growth inhibition and calpain/caspase-12 dependent apoptosis in PDGF cultured 3T6 fibroblast.

Previous studies have demonstrated that arachidonic acid (AA) metabolites released by the cyclooxygenase pathway is involved in serum-induced 3T6 fibroblast cycle progression and proliferation. However, these results also suggest that other AA cascade pathways might be involved. Recently, we also described the role of hydroxyeicosatetraenoic acids, which are produced by cytochrome P450 monooxygenases (CYP), in 3T6 fibroblast growth. AA can be also metabolized by the epoxygenase activity of CYP-producing epoxyeicosatrienoic acids (EETs). Finally, the cytosolic epoxide hydrolases catalyze the hydration of the EETs, transforming them into dihydroxyeicosatetraenoic acids (DHETEs). In this work, we have studied the role of the EETs/DHETEs on 3T6 fibroblasts growth. Our results show that PDGF stimulates 3T6 fibroblast proliferation and [3H]thymidine incorporation, while the addition of 5,6-EET, 8,9-EET, 11,12-EET or 14,15-EET (0.1-1 microM) inhibit these processes. Furthermore, 5,6-DHETE and 11,12-DHETE (0.1-1 microM) also inhibit cell proliferation and DNA synthesis. Interestingly, this growth inhibition was correlated with an induction of apoptosis. Thus, we observed that in the presence of PDGF, EETs or DHETEs (0.1-1 microM) induce phosphatidylserine externalization (as measured by annexin V-binding) and DNA fragmentation (as quantified using a TUNEL assay). Our results show that calpain, as well as caspase-12 and caspase-3, are involved in these events. Therefore, EETs and DHETEs have anti-proliferative and pro-apoptotic effects on PDGF-stimulated 3T6 fibroblasts.

Hydroxyeicosatetraenoic acids released through the cytochrome P-450 pathway regulate 3T6 fibroblast growth.

Eicosanoids participate in the regulation of cellular proliferation. Thus, we observed that prostaglandin E(2) interaction with membrane receptors is involved in the control of 3T6 fibroblast growth induced by serum. However, our results suggested that another arachidonic acid pathway might be implicated in these events. Our results show that 3T6 fibroblasts synthesized hydroxyeicosatetraenoic acids (HETEs) such as 12-HETE through the cytochrome P-450 (CYP450) pathway. However, 3T6 fibroblasts did not produce leukotriene B(4) (LTB(4)), and lipoxygenase inhibitors and LT antagonists failed to inhibit 3T6 fibroblast growth induced by FBS. In contrast, we observed that CYP450 inhibitors such as SKF-525A, 17-octadecynoic acid, 1-aminobenzotriazole, and 6-(2-propargyloxyphenyl)hexanoic acid reduced 12(S)-HETE levels, 3T6 fibroblast growth, and DNA synthesis induced by FBS. The impairment of DNA synthesis and 3T6 fibroblast growth induced by SKF-525A were reversed by exogenous addition of HETEs. Moreover, we report that 5-HETE, 12(S)-HETE, and 15(S)-HETE are mitogenic on 3T6 fibroblast in the absence of another growth factor, and this effect was dependent on the activation of the phosphatidylinositol-3-kinase pathway. In conclusion, our results show that HETEs, probably produced by CYP450, are involved in the control of 3T6 fibroblast growth.

Effect of arachidonic and eicosapentaenoic acid metabolism on RAW 264.7 macrophage proliferation.

Prostaglandins (PGs) and leukotrienes (LTs) derived from arachidonic acid (AA) are potent mediators of inflammation and cell proliferation. Dietary intake of eicosapentaenoic acid (EPA) appears beneficial to both inflammatory processes and cell proliferation. However, there is no clear mechanism explaining these effects. In this study, we investigated the effect of EPA on the AA incorporation in phospholipid membranes, on AA release and metabolism, and consequently, on PG synthesis. Our results showed not only that [(3)H]AA and [(14)C]EPA were similar incorporated into RAW 264.7 macrophage membranes, but also that the redistribution pattern between phospholipids was alike. [(3)H]AA or [(14)C]EPA release was induced by fetal bovine serum (FBS) in a similar fashion with AA metabolizing 3-fold more than EPA. In this way, we observed that AA could be metabolized by cyclooxygenase (COX)-1, COX-2 and 5-lipoxygenase (5-LOX) whereas EPA was metabolized by COX-2 and 5-LOX pathways. Moreover, both fatty acids were able to induce COX-2 expression. When we incubated [(3)H]AA labeled cells with exogenous EPA, we observed that EPA did not modify FBS-induced [(3)H]AA release but that the presence of EPA decreased [(3)H]AA metabolism and therefore PGE(2) synthesis. Moreover, we studied the effect of AA and EPA metabolites on macrophage proliferation. Our results showed that PGE(3) stimulated cell growth with a potency similar to that of PGE(2), whereas LTB(5) was less effective than LTB(4). These data suggest that the effects of EPA on cell growth might be attributable, at least in part, to the marked decrease of eicosanoid release.

Evaluación económica de tramadol/paracetamol en el manejo del dolor en pacientes con osteoartrosis en España / Economic evaluation of tramadol/paracetamol in the management of pain in patients with osteoarthritis in Spain

Objetivo. Comparar el coste del tratamiento del dolor en la osteoartrosis (OA) con tramadol/paracetamol frente a los antiinflamatorios no esteroideos (AINE) solos o en combinación con un inhibidor de la bomba de protones (IBP) desde el punto de vista del Sistema Nacional de Salud de España. Métodos. Se realizó un modelo analítico de decisiones que evaluó los costes derivados de las tres estrategias de tratamiento durante 6 meses. Se utilizó un análisis de minimización de costes considerando datos referentes al uso de recursos, costes farmacológicos y costes derivados del tratamiento de los acontecimientos adversos (AA) de la medicación. Resultados. En el análisis del caso base, el coste del tratamiento del dolor de la OA durante 6 meses con tramadol/paracetamol fue de 232,86 €, comparado con 274,60 € con los AINE + IBP y 133,75 € con los AINE solos. Por tanto, el tratamiento con tramadol/paracetamol produce un ahorro de 41,74 € por paciente durante 6 meses respecto a AINE + IBP y un coste adicional de 99,11 € respecto a los AINE solos. Al considerar los AA renales, tramadol/paracetamol produce un ahorro comparado con los tratamientos que contienen AINE (140,02 € respecto de los AINE solos y 280,86 € respecto de los AINE + IBP). Conclusiones. Basándose en los resultados de un modelo teórico analítico de decisiones, los datos sugieren que tramadol/paracetamol produce ahorros comparado con los AINE + IBP en el tratamiento del dolor de la OA durante 6 meses. Tramadol/paracetamol también produce ahorros comparado con los AINE solos si se consideran los AA renales (AU)

Objective. To compare the costs of treating osteoarthritis (OA) pain using combination tramadol/paracetamol tablets, Non-Steroidal Anti-Inflammatory Agents (NSAID) alone or NSAID plus proton pump inhibitors (PPI) from the perspective of the Spanish National Health System. Methods. A decision-analytical model was constructed to analyze the cost associated with three treatment strategies over 6 months. A cost-minimization approach was used, which considered data related to resource use, medication costs and costs for the treatment of adverse events. Results. In the base-case analysis, costs for 6 months of treatment of OA pain using tramadol/paracetamol were €232.86, compared with €274.60 for NSAID + PPI and €133.75 for NSAID alone. This provided a savings of €41.74 per patient over 6 months for tramadol/paracetamol compared with NSAID + PPI and a cost increase of €99.11 compared with NSAID alone. When renal adverse events associated with NSAID were considered, tramadol/paracetamol was cost saving compared with all NSAID-based regimens (saving €140.02 vs NSAID alone, €280.86 vs NSAID + PPI). Conclusion. Based on the results of a theoretical decision-analytic model, the data obtained may suggest that tramadol/paracetamol is cost saving compared with NSAID + PPI for the treatment of OA pain over a period of 6 months. Tramadol/paracetamol is also cost saving compared with treatment with NSAID alone if considering renal adverse events (AU)

Análisis de minimización de costes de fludarabina (Beneflur®) oral vs. vía intravenosa en España / Cost-reduction analysis for oral versus intravenous fludarabine (Beneflur®) in Spain

Introducción: Fludarabina ha demostrado su eficacia, seguridad y eficiencia en el tratamiento de la leucemia linfocítica crónica de células B (LLC-B) en diversos estudios internacionales. El objetivo del presente estudio fue realizar un análisis de minimización de costes de 2 formas alternativas de fludarabina (oral e intravenosa) para el tratamiento de la LLC-B en España. Métodos: La existencia de evidencias clínicas sobre la equivalencia terapéutica de las 2 opciones comparadas (fludarabina oral frente a fludarabina intravenosa) llevó a la realización de un análisis de minimización de costes. Se construyó un modelo farmacoeconómico que combinó datos de la bibliografía y la opinión de expertos para determinar el uso de recursos sanitarios asociados al tratamiento, y los costes unitarios se obtuvieron de bases de datos españolas. El análisis consideró 2 perspectivas: a) la del Sistema Nacional de Salud, que incluía sólo los costes directos sanitarios, y b) la perspectiva social, que además de éstos, incluía los costes indirectos derivados de la pérdida de productividad. Resultados: Aunque la forma oral de fludarabina tiene un coste de adquisición mayor que la especialidad farmacéutica genérica de fludarabina intravenosa, los mayores costes de administración de esta última, de uso hospitalario, se tradujeron en unos ahorros totales asociados a fludarabina oral de 1.908 y 1.292 € en monoterapia y tratamiento combinado con ciclofosfamida, respectivamente. La inclusión de los costes indirectos aumentó los ahorros asociados a la forma oral. Conclusiones: El tratamiento de los pacientes con LLC-B con fludarabina oral presenta unos costes menores respecto a fludarabina intravenosa, tanto en monoterapia, como en tratamiento combinado. Diversos análisis de sensibilidad confirmaron estos resultados, en los que se constata que la forma oral de fludarabina debería ser la opción de elección en el tratamiento de la LLC-B en España, salvo que se contraindique (AU)

Introduction: Various international studies have shown that fludarabine is effective, safe, and efficient for treating B-cell chronic lymphocytic leukemia (B-CLL). The purpose of the present study was to carry out a cost-minimization analysis for two alternative forms of fludarabine (oral and intravenous) used to treat B-CLL in Spain. Methods: The presence of clinical evidence about the treatment equivalence of the two options being compared (oral fludarabine vs. intravenous fludarabine) led us to carry out a cost-minimization analysis. A pharmacoeconomic model was constructed to compile data from the literature and experts’ opinions in order to determine the use of health resources associated with the treatment; unit costs were obtained from Spanish databases. The analysis contemplated two perspectives: that of the national health service, which includes only direct health costs, and the social perspective, which also includes the indirect costs that result from loss of productivity. Results: Although fludarabine in its oral form has a higher purchase price than generic intravenous fludarabine does, increased administration costs for the latter, which is used in hospitals, mean that oral fludarabine use produces total savings of €1,908 and €1,292 for single-drug therapy and combined therapy with cyclophosphamide, respectively. Including indirect costs increased the savings associated with the oral form of the drug. Conclusions: In B-CLL patients, treatment with oral fludarabine has a lower cost than treatment with intravenous fludarabine, in both single-drug therapy and combined therapy. Various sensitivity analyses confirmed these results and showed that oral fludarabine should be the treatment of choice for B-CLL in Spain, unless contrain (AU)