Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients.

BACKGROUND: The DRCR.net Protocol T clinical trial assessed the comparative efficacy and safety of anti-VEGF treatments including aflibercept, ranibizumab and bevacizumab in diabetic macular edema (DME). Post -hoc analyses showed that after a 12-week induction period, there was still DME resolution in an increasing number of patients through week 24. PURPOSE: To assess clinical and cost consequences of extending the anti-VEGF loading dose from 3 to 6 monthly injections in patients with persistent DME in Spain. METHODS: From a hospital pharmacy perspective, a cost-consequence analysis model was developed to estimate the incremental cost needed to obtain an additional response at month 6. To estimate drug treatment costs, ex-factory prices (€, 2019) were considered for aflibercept, ranibizumab and bevacizumab. Response/nonresponse rates at 3/6 months were obtained from the Protocol T 24-week post hoc analysis (n = 546). Persistent DME was present in 50.8 and 31.6% of the 190 aflibercept-treated patients at month 3 and month 6, respectively. Of the 176 ranibizumab- and 180 bevacizumab-treated patients, 53.2 and 72.9%, respectively, had persistent DME at month 3, and 41.5 and 65.6%, respectively, had persistent DME at month 6. Sensitivity analysis considered the split of bevacizumab vials. RESULTS: Extending the loading dose in nonresponder patients would cost €214,862.57, €208,488.98 and €134,483.16 to obtain 37, 21 and 13 additional aflibercept, ranibizumab and bevacizumab responder patients, respectively. The total number of extended injections (months 3-6) used in patients with persistent DME at month 6 was 180, 219 and 354 for aflibercept, ranibizumab and bevacizumab, respectively. CONCLUSIONS: To extend the anti-VEGF loading dose from 3 to 6 injections necessitates investing €5882.77 (8 injections), €10,091.03 (14 injections) and €10,198.59 (30 injections) per additional responder patient (3-month nonresponders and 6-month responders) to aflibercept, ranibizumab and bevacizumab, respectively. For the total of patients treated, on average €7927.02 (14 injections) per additional responder patient would be needed.

Cost-effectiveness analysis of treatment sequences containing tofacitinib for the treatment of rheumatoid arthritis in Spain.

OBJECTIVE: To assess the cost-effectiveness of tofacitinib-containing treatment sequences versus sequences containing only standard biological therapies in patients with moderate-to-severe rheumatoid arthritis (RA) after the failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR population) and in patients previously treated with methotrexate (MTX) who show an inadequate response to second-line therapy with any tumour necrosis factor inhibitor (TNFi-IR population). METHODS: A patient-level microsimulation model estimated, from the perspective of the Spanish Public NHS, lifetime costs and quality-adjusted life years (QALY) for treatment sequences starting with tofacitinib (5 mg twice daily) followed by biological therapies versus sequences of biological treatments only. Concomitant treatment with MTX was considered. Model's parameters comprised demographic and clinical inputs (initial Health Assessment Questionnaire [HAQ] score and clinical response to short- and long-term treatment). Efficacy was measured by means of HAQ score changes using mixed treatment comparisons and data from long-term extension (LTE) trials. Serious adverse events (SAEs) data were derived from the literature. Total cost estimation (€, 2018) included drug acquisition, parenteral administration, disease progression and SAE management. RESULTS: In the csDMARD-IR population, sequences starting with tofacitinib proved dominant options (more QALYs and lower costs) versus the corresponding sequences without tofacitinib. In the TNFi-IR population, first-line treatment with tofacitinib+MTX followed by scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX proved dominant versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX; and tofacitinib+MTX➔scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX was less effective but remained a cost-saving option. CONCLUSIONS: Inclusion of tofacitinib seems a dominant strategy in moderate-to-severe RA patients after csDMARDs failure. Tofacitinib, as initial third-line therapy, proved a cost-saving strategy (€- 337,489/QALY foregone) in moderate-to-severe TNFi-IR RA patients. Key points • Therapeutical approach in rheumatoid arthritis (RA) consisted in sequences of several therapies during patient lifetime. • Treatment sequences initiating with tofacitinib followed by biological drugs provided higher health effects in csDMARDs-IR population, compared with sequences containing only biological drugs. • In both csDMARD-IR and TNFi-IR RA populations, initiating treatment with tofacitinib was associated to lower treatment costs for the Spanish National Health System.

Situación del tratamiento anticoagulante oral en pacientes con fibrilación auricular no valvular en España. Estudio REACT-AF / Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF Study

Antecedentes y objetivos: La terapia anticoagulante oral resulta compleja dadas las necesidades de control y el riesgo hemorrágico que conlleva. Este estudio pretende determinar la práctica clínica habitual del tratamiento para la prevención del ictus en pacientes con fibrilación auricular no valvular (FANV) en España. Pacientes y método: El Real Evidence of Anti Coagulation Treatment in AF es una cohorte multicéntrica, europea, multinacional, observacional, de seguimiento retrospectivo, de pacientes con FANV. En este estudio se incluye a los pacientes reclutados en España con al menos una visita en el periodo de inclusión (mayo 2010/abril 2012). Se evaluaron: a) la persistencia del tratamiento con anticoagulantes orales (tiempo hasta discontinuación); b) la tasa de persistencia (porcentaje de pacientes en tratamiento) a los 6, 12 y 24 meses, y 5 años; c) la adherencia terapéutica (tasa de posesión de medicación); d) la concordancia entre el tratamiento seguido y el recomendado según la Sociedad Europea de Cardiología; y e) la incidencia de ictus y eventos hemorrágicos. Resultados: Los pacientes tratados con anticoagulantes orales (n=7.526) presentaron un tiempo hasta discontinuación del tratamiento de 1,99 años (mediana) y una tasa de persistencia a 5 años del 26% (discontinuación ≥3 meses). La adherencia (tasa de posesión de medicación media) fue 0,54±0,36. La incidencia de ictus fue 0,3/100 personas-año y la de eventos hemorrágicos, 2,4/100 personas-año. El 58% de los pacientes con FANV (n=12.514) seguía las recomendaciones de la Sociedad Europea de Cardiología. Conclusión: El 42% de los pacientes con FANV no seguía las recomendaciones de la Sociedad Europea de Cardiología. Se detectó una baja persistencia y adherencia al tratamiento con anticoagulantes orales (AU)

Background and objectives: Oral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. Patients and method: The Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. Results: The patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. Conclusion: Forty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants (AU)

Use of healthcare resources and costs of acute cardioembolic stroke management in the Region of Madrid: The CODICE Study.

INTRODUCTION: Stroke is the main cause of admission to Neurology departments and cardioembolic stroke (CS) is one of the most common subtypes of stroke. METHODS: A multicentre prospective observational study was performed in 5 Neurology departments in public hospitals in the Region of Madrid (Spain). The objective was to estimate the use of healthcare resources and costs of acute CS management. Patients with acute CS at<48h from onset were recruited. Patients' socio-demographic, clinical, and healthcare resource use data were collected during hospitalisation and at discharge up to 30 days after admission, including data for rehabilitation treatment after discharge. RESULTS: During an 8-month recruitment period, 128 patients were recruited: mean age, 75.3±11.25; 46.9% women; mortality rate, 4.7%. All patients met the CS diagnostic criteria established by GEENCV-SEN, based on medical history or diagnostic tests. Fifty per cent of the patients had a history of atrial fibrillation and 18.8% presented other major cardioembolic sources. Non-valvular atrial fibrillation was the most frequent cause of CS (33.6%). Data for healthcare resource use, given a mean total hospital stay of 10.3±9.3 days, are as follows: rehabilitation therapy during hospital stay (46.9%, mean 4.5 days) and after discharge (56.3%, mean 26.8 days), complications (32%), specific interventions (19.5%), and laboratory and diagnostic tests (100%). Head CT (98.4%), duplex ultrasound of supra-aortic trunks (87.5%), and electrocardiogram (85.9%) were the most frequently performed diagnostic procedures. Average total cost per patient during acute-phase management and rehabilitation was €13,139. Hospital stay (45.0%) and rehabilitation at discharge (29.2%) accounted for the largest part of resources used. CONCLUSIONS: Acute CS management in the Region of Madrid resulted consumes large amounts of resources (€13,139), mainly due to hospital stays and rehabilitation.

Status of oral anticoagulant treatment in patients with nonvalvular atrial fibrillation in Spain. REACT-AF Study. / Situación del tratamiento anticoagulante oral en pacientes con fibrilación auricular no valvular en España. Estudio REACT-AF.

BACKGROUND AND OBJECTIVES: Oral anticoagulant therapy is complex due to the need for control and the hemorrhagic risk the therapy entails. This study aims to determine the standard clinical practice in the treatment for preventing stroke in patients with nonvalvular atrial fibrillation (NVAF) in Spain. PATIENTS AND METHOD: The Real Evidence of Anti Coagulation Treatment in AF is a European, multicenter, multinational, observational, retrospectively monitored cohort of patients with NVAF. This study included patients recruited in Spain with at least one visit during the period of inclusion (May 2010/April 2012). The study evaluated the following: a) persistence of oral anticoagulant treatment (time to discontinuation); b) persistence rate (% of patients in treatment) at 6, 12 and 24 months and at 5 years; c) therapeutic compliance (medication possession ratio); d) the correlation between the treatment followed and that recommended by the European Society of Cardiology; and the incidence of stroke and hemorrhagic events. RESULTS: The patients treated with oral anticoagulants (n=7,526) had a median time to discontinuation of treatment of 1.99 years and a persistence rate at 5 years of 26% (discontinuation ≥3 months). The compliance (mean MPR) was 0.54±0.36. The incidence of stroke was 0.3/100 person-years, and the incidence of hemorrhagic events was 2.4/100 person-years. Fifty-eight percent of the patients with NVAF (n=12,514) followed the recommendations of the European Society of Cardiology. CONCLUSION: Forty-two percent of the patients with NVAF did not follow the recommendations of the European Society of Cardiology. We detected low persistence and treatment compliance rates for oral anticoagulants.

[Cost analysis of the use of botulinum toxin type A in Spain]. / Análisis de costes del uso de toxina botulínica A en España.

OBJECTIVE: To estimate treatment costs of blepharospasm, cervical dystonia(CD), upper limb spasticity (ULS) and spasticity in children with cerebral palsy (SCCP) with botulinum neurotoxin type A (BoNT-A) in Spain. METHOD: Annual BoNT-A treatment costs were calculated (2013 ex-factory price () applying RDL 8/2010 and RDL 9/2011 deductions), based on initial dose (id), average dose (ad) and maximum dose (md) according to Summary of Product Characteristics of Botox® (100U/50U), Dysport®(500U) and Xeomin® (100U) and considering the use of complete vials.In addition, annual treatment costs were calculated considering the useof vials in more than one patient and also patient population annual treatment costs based on diseases' prevalence. RESULTS: Annual BoNT-A treatment costs per patient were estimated at between 265 and 2,120 with savings from 10% to 55% accordingto the selected BoNT-A. CD and ULS treatment provided the greatest cost per patient. Botox® provided greater savings in ULS (id/ad), CD(id), and in blepharospasm and SCCP (id/ad/md). Dysport® treatment was less costly in CD (md) and ULS (md), while Xeomin® was in CD(ad). Based on the estimated treated population in Spain, the annual treatment costs ranged from 368,392 to 13,958,836 depending on indication, dose and BoNT-A considered. CONCLUSIONS: The appropriate BoNT-A choice would lead to considerable savings for the National Health System. Botox® would generate lower costs per patient than other BoNT-A products in 9 out of 12 scenarios considered.

Objetivo: Estimar el coste de tratamiento de blefarospasmo, distoníacervical (DC), espasticidad del brazo del adulto (EBA) yespasticidad del niño con parálisis cerebral infantil (EPCI) con laspresentaciones de neurotoxina botulínica tipo A (NTB-A) enEspaña.Método: Se calculó el coste anual de tratamiento con NTB-A(, 2013; PVL oficial publicado aplicando deducciones del RDL8/2010 y RDL 9/2011), en función de la dosis inicial (di), dosismedia (dm) y dosis máxima (dmax) en base a los viales porsesión según fichas técnicas de Botox® (100U y 50U), Dysport®(500U) y Xeomin® (100U), considerando los músculos comunesen cada indicación. Adicionalmente, se calculó el coste considerandola población total de pacientes según prevalencia y lareutilización de viales en más de un paciente.Resultados: El coste anual/paciente con NTB-A supondría entre265y 2.120con un ahorro entre el 10% y 55% según laNTB-A seleccionada. DC y EBA presentarían el mayor coste/paciente. Botox® generaría un menor coste en EBA (di/dm) y DC(di) y en blefarospasmo y EPCI (di/dm/dmax). Dysport® tiene elmenor coste en DC (dmax) y EBA (dmax) y Xeomin® en DC(dm). El coste anual por población según prevalencia suponeentre 368.392y 13.958.836según indicación, dosis y NTBAseleccionada.Conclusiones: Una selección adecuada de las presentaciones deNTB-A para cada indicación permitiría generar importantesahorros para el Sistema Nacional de Salud. Botox® conseguiríamenores costes anuales/paciente frente al resto de NTB-A en 9de los 12 escenarios considerados.