Medication guide for dose adjustment and management of cardiotoxicity and lipid metabolic adverse events of oral antineoplastic therapy.

Objective: The management of cardiotoxicity concerning the use of oral antineoplastic agents (OAAs) is a challenge for healthcare professionals. Our objective was to create a comprehensive medication management guide with dose adjustment recommendations on OAAs concerning cardiotoxic and lipid metabolic adverse events (AEs) to assist healthcare professionals when prescribing OAAs. Materials and methods: A review of the available information on all dose adjustments necessary to safely prescribe and dispense OAAs concerning cardiotoxicity was conducted. In January 2023, we identified all OAAs authorized by the European Medicines Agency (EMA). For each drug, the latest summary of product characteristics (SPC) approved by the EMA and the tertiary data source Lexicomp® were reviewed. Cardiotoxic AEs were recorded, namely, QT interval prolongation, decrease in left ventricular ejection fraction (LVEF), imbalances in blood pressure (hypertension and hypotension), alterations in heart rate (tachycardia and bradycardia), and thrombosis. Any available dose adjustment recommendations in case of an occurrence of these adverse events were collected. Results: In all, 93 different OAAs had been approved by the EMA and were reviewed. Among them, 51.6% have recognized cardiotoxic AEs and 10.8% can cause alterations in lipid metabolism. A total of 27 (29.0%) OAAs had specific recommendations regarding QT prolongation; 88.9% were listed in the SPC and 59.3% in Lexicomp®. Eight OAAs (9.68%) have reported a decrease in LVEF, and four of these drugs, namely, encorafenib, lorlatinib, ripretinib, and sunitinib, have specific management recommendations. Almost half (49.5%) of currently approved OAAs can potentially alter blood pressure; 34 (36.6%) of them have been reported to cause hypertension and 12 (12.9%) are related to hypotension. Tachycardia and/or bradycardia are associated with 22.6% and 8.6% of the evaluated drugs, respectively. Regarding thrombosis, 30 (32.3%) of the drugs analyzed included the appearance of a thrombus as a possible AE. Conclusions: More than half of the OAAs can produce cardiotoxic effects, with the most frequent being blood pressure alteration and QT interval prolongation with a non-depreciable incidence of LV dysfunction or thrombosis. Before starting the treatment, it is necessary to stratify baseline cardiovascular risk, plan a surveillance schedule, and consider referral to cardio-oncology units.

Anti-interleukin-17 therapies for moderate/severe psoriasis in clinical practice: effectiveness, safety and association with clinical patient factors.

OBJECTIVES: Interleukin-17 (IL-17) contributes to the pathogenesis of psoriasis. Secukinumab, ixekizumab, and brodalumab are monoclonal antibodies anti-IL-17 antibodies, approved for the treatment of moderate/severe plaque psoriasis.The aim of the study was to describe the effectiveness and safety of anti-IL-17 agents in moderate/severe plaque psoriasis in clinical practice. We also analysed anti-IL-17 therapies' survival, dose adjustment, and clinical patients' factors associated with their effectiveness and safety. METHODS: A retrospective, longitudinal study was conducted at a tertiary hospital. We included patients with moderate/severe psoriasis treated with anti-IL-17 agents. The effectiveness was evaluated with Psoriasis Area and Severity Index (PASI) score and safety through the adverse drug reactions (ADRs) collected. RESULTS: 38 patients were studied (median age=47.4 years, 71.0% male). The mean number of biological therapies that patients received was 2.6, and anti-IL-17 therapy was the first biological therapy for 36.8% of patients. The median years in treatment were 2.5 (95% CI 1.95 to 2.98) for secukinumab, 1.2 (95% CI 0.36 to 1.47) for ixekizumab, and 0.7 (IQR 0.71) for brodalumab. The median PASI score after 6 months of treatment was 0 (IQR 0) and 85.3% of patients achieved a PASI of 90 (84.0% with secukinumab, 87.5% with ixekizumab, and 100% with brodalumab). Dose adjustment was associated with the line of treatment (p=0.034 for naïve patients), age (p=0.044 for younger patients), and concomitant pathologies (p=0.015 without more diseases).24 patients suffered from ADRs, mainly infections of the upper respiratory tract, and there were no statistically significant differences between the three therapies. CONCLUSIONS: Anti-IL-17 agents constitute an effective treatment for patients with moderate/severe plaque psoriasis and for longer. Dose reductions were associated with fewer lines of treatment, younger patients and absence of concomitant pathologies. ADR were minor and similar among the anti-IL-17.

Cost-effectiveness of adjuvant atezolizumab versus best supportive care in the treatment of patients with resectable early-stage non-small cell lung cancer and overexpression of PD-L1.

AIMS: To assess the cost-effectiveness of adjuvant atezolizumab in the treatment of early-stage NSCLC patients (stage II-IIIA) with expression PD-L1 ≥ 50% without mutations in EGFR or ALK rearrangements in Spain. MATERIALS AND METHODS: A 5-states Markov model (DFS, locoregional recurrence, 1 L-metastatic recurrence, 2 L-metastatic recurrence, and death states) was adapted to the Spanish setting. Demographic characteristics of the hypothetical cohort, transition probabilities from the DFS state, and safety parameters were obtained from IMpower010 study (GO29527). Transition probabilities from locoregional and metastatic health states were obtained from the literature. The usual clinical practice in Spain (use of health resources, management of the disease, etc.) was obtained from a previous analysis carried out by the authors of this study. A societal perspective was considered so both direct and indirect costs were included (expressed in € of 2021). A lifetime horizon was used, so costs and health outcomes were discounted at 3% per year. Sensitivity analyses were performed to evaluate uncertainty. RESULTS: Over a lifetime horizon, treatment with adjuvant atezolizumab provided greater effectiveness (+2.61 life years [LY] and +1.95 quality-adjusted life years [QALY]) and higher cost (€+22,538) than BSC. The incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratios (ICUR) of the analysis were €8,625/LY gained and €11,583/QALY gained, respectively. Robustness of these base-case results was confirmed by the sensitivity analyses performed. In the probabilistic sensitivity analysis, 90% of the simulations performed showed that adjuvant atezolizumab is cost-effective versus BSC, considering a threshold of €30,000/QALY. CONCLUSIONS: Our results showed that adjuvant treatment with atezolizumab in patients with early-stage resected NSCLC with overexpression of PD-L1 and without EGFR and ALK mutations is cost-effective versus BSC as the ICERs and ICURs obtained are below the cost-effectiveness thresholds commonly considered in Spain, thus offering a new treatment alternative for these patients.

Economic burden of locoregional and metastatic relapses in resectable early-stage non-small cell lung cancer in Spain.

BACKGROUND: There are scarce data of the costs of non-small cell lung cancer (NSCLC) recurrence in Spain. The objective of this study is to assess the economic burden of disease recurrence, for both locoregional and/or metastatic relapses, after appropriate early-stage NSCLC treatment in Spain. MATERIALS AND METHODS: A two-round consensus panel of Spanish oncologists and hospital pharmacists was conducted to collect information on patient's flow, treatments, use of healthcare resources and sick leaves in patients with relapsed NSCLC. A decision-tree model was developed to calculate the economic burden of disease recurrence after appropriate early-stage NSCLC. Both direct and indirect costs were considered. Direct costs included drug acquisition and healthcare resources costs. Indirect costs were estimated using the human-capital approach. Unit costs were obtained from national databases (euros of 2022). A multi-way sensitivity analysis was performed to provide a range to the mean values. RESULTS: Among a cohort of 100 patients with relapsed NSCLC, 45 patients would have locoregional relapse (36.3 would eventually progress to metastasis and 8.7 would be considered in remission) and 55 patients would have metastatic relapse. Over time, 91.3 patients would experience a metastatic relapse (55 as first relapse and 36.6 after previous locoregional relapse). The overall cost incurred by the 100-patients cohort is €10,095,846 (€9,336,782 direct costs, €795,064 indirect costs). The average cost of a locoregional relapse is €25,194 (€19,658 direct costs, €5536 indirect costs), while the average cost a patient with metastasis who receives up to 4 lines of treatment is €127,167 (€117,328 direct, €9839 indirect). CONCLUSIONS: To our knowledge, this is the first study that specifically quantifies the cost of relapse in NSCLC in Spain. Our findings shown that the overall cost of a relapse after appropriate treatment of early-stage NSCLC patients is substantial, and it increases considerably in the metastatic relapse setting, mainly due to the high cost and long duration of first-line treatments.

Complementary and alternative medicine in cancer patients: characteristics of use and interactions with antineoplastic agents.

PURPOSE: Our objectives were to analyze the use of complementary and alternative medicine (CAM) in cancer patients and to describe the incidence and characteristics of interactions between CAM and antineoplastic agents. METHODS: We performed an observational study in cancer outpatients at a university hospital. Variables were collected through a 22-item questionnaire. Potential interactions between CAM and antineoplastic agents were analyzed using the Lexicomp®, the About Herbs®, and the summary of product characteristics. Mechanism of action, reliability, and the potential clinical effect of interactions were analyzed. RESULTS: The study population comprised 937 patients, of whom 65% used CAM (70.6% herbal products, 25.8% dietary supplements, and 3.6% homeopathy). Female sex, younger age, and breast cancer were associated with more frequent use of CAM. The primary source of information about CAM was friends and family (43.5%). A total of 335 (57.1%) patients did not tell their doctor that they took CAM. The five most common CAM were chamomile, green tea, pennyroyal mint, linden, and rooibos. At least one interaction between CAM and antineoplastic agents was reported by 65.0% of CAM users (33.9% of all patients). Depending on the mechanism of action, 80% of CAM diminished the metabolism of the antineoplastic agents. CONCLUSION: Our results reveal a high incidence of interactions between CAM and antineoplastic agents. The most frequent CAM were herbal products. Family and friends were the primary sources of information that led patients to start taking CAM, and more than half of the patients did not tell their doctor that they were taking CAM.

Possible heart failure caused by osimertinib in a lung cancer patient.

INTRODUCTION: Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of epidermal growth factor receptor mutated non-small cell lung cancer (NSCLC). It has demonstrated better results concerning effectiveness than other TKIs for the same indication. However, despite a good safety profile, it could produce some cardiotoxicity that does not occur with other drugs of the same group. CASE REPORT: We report the evolution and management of a female patient diagnosed with NSCLC who developed a grade 3 cardiotoxicity due to treatment with osimertinib. This patient suffered from a left bundle branch block, dyslipidemia, and hypertension as cardiovascular risk factors. After a long period of treatment with osimertinib, she developed a severe heart failure (HF) with an important decrease in left ventricular ejection fraction (LVEF), which triggered an admission to the oncology unit for eight days. MANAGEMENT AND OUTCOMES: Treatment with osimertinib was first suspended and then resumed after stabilization of the HF. She also developed atrial fibrillation during admission and has required narrow cardiac monitoring and management since the debut of the HF. After evaluating the benefit-risk balance, osimertinib was reintroduced and the patient continues in treatment at the moment, although the baseline LVEF is not recovered. DISCUSSION: There is scarce evidence in the literature concerning HF and important LVEF decrease due to osimertinib. However, its severity and repercussion for the patient justify the thorough screening of cardiovascular risk factors before starting the therapy.

Implementation and evaluation of a home pharmaceutical care model through Telepharmacy.

OBJECTIVE: To describe the impact of a Specialized Pharmaceutical Care model  that includes pharmacotherapeutic monitoring of patients through an  Telepharmacy platform and home medication dispensing. METHOD: A descriptive and retrospective study conducted in the Pharmacy Service of a tertiary hospital, between 23 March 2020 and 31  December 2021. A new pharmaceutical care model for chronic ambulatory  patients was developed, including: (i) definition of criteria for selecting  Telepharmacy candidate patients; (ii) stratification of patients by risk level; (iii)  definition of individualized pharmacotherapeutic monitoring; (iv)  adaptation of the Pharmacy Service app platform to ensure continuous pharmacotherapeutic monitoring and patient monitoring (e- Oncohealth, e-Midcare and farMcuida), (v) implementation of an appointment  system; and (vi) development of a software module for the management of  home medication delivery. The impact of this pharmaceutical care model was assessed by analyzing indicators of activity, safety, adherence and  perceived quality. Moreover, an additional study on the impact of COVID­19 was developed in order to assess the accessibility of medical care  and continuity of treatment through a survey conducted on a random sample of 100 patients. RESULTS: During the study period, 2,737 patients benefited from the new  remote pharmaceutical care model. A total of 7,758 Telepharmacy consultations were performed. Pharmacotherapeutic monitoring  prevented 1,043 adverse drug reactions, which affected 10.4% of patients  (3.6 adverse drug reactions/patient). Mean adherence to treatment  was 95.2%. Overall satisfaction with the new model was 9.8/10. All patients would recommend this model to other patients. CONCLUSIONS: The new Pharmaceutical care model increases patient safety and  improves treatment adherence, with a high perceived quality. Patient  stratification and individualized follow-up via an Telepharmacy platform were  crucial to the development of this model.

OBJETIVO: Describir el impacto de un modelo de atención farmacéutica especializada que incluye el seguimiento farmacoterapéutico de  los pacientes mediante una plataforma de Telefarmacia y la dispensación de  la medicación en el domicilio.Método: Estudio descriptivo, retrospectivo, llevado a cabo en un servicio de  farmacia de un hospital terciario entre el 23 marzo de 2020 y el 31 de  diciembre de 2021. Se desarrolló un nuevo modelo de atención farmacéutica para la atención de los pacientes crónicos ambulatorios, que incluye: i) definición de los criterios de selección de los pacientes  candidatos a Telefarmacia, ii) estratificación de los pacientes según el nivel de riesgo, iii) definición del seguimiento farmacoterapéutico individualizado, iv)  adaptación de la plataforma de apps del servicio de  farmacia para garantizar el seguimiento farmacoterapéutico continuo y la  monitorización de los pacientes (e-Oncosalud, e-Midcare y farMcuida), v)  implantación de un sistema de citación, y vi) el desarrollo de un módulo  informático para la gestión de la dispensación y entrega de la medicación en el  domicilio. El impacto de este modelo de atención se evaluó mediante el análisis  de indicadores de actividad, seguridad, adherencia y calidad percibida.  Asimismo, se incluyó un estudio adicional sobre el impacto de la  COVID­19 en  la accesibilidad de la atención médica y la continuidad de los  tratamientos, mediante una encuesta a una muestra aleatoria de 100  pacientes. RESULTADOS: Durante el periodo de estudio, 2.737 pacientes se han beneficiado del nuevo modelo de atención farmacéutica a distancia. El número de consultas de Telefarmacia realizadas fue 7.758. El seguimiento  farmacoterapéutico evitó 1.043 eventos adversos asociados a la  medicación, que afectaron al 10,4% de los pacientes atendidos (3,6 eventos  adversos asociados a la medicación/paciente). La adherencia media al  tratamiento de los pacientes fue del 95,2%. La satisfacción global con el nuevo  modelo de atención farmacéutica fue de 9,8/10. El 100% de los  pacientes lo recomendaría a otros pacientes. CONCLUSIONES: Este nuevo modelo de atención farmacéutica aumenta la  seguridad del paciente y mejora su adherencia al tratamiento, con unos índices  de calidad percibida elevados. La estratificación de pacientes y el  seguimiento personalizado mediante la plataforma Telefarmacia resultaron clave en su desarrollo.

A smartphone app to improve the safety of patients undergoing treatment with oral antineoplastic agents: 4 years of experience in a university hospital.

Objective: This study aims to analyze the impact of the eOncosalud app on the management and follow-up of adverse effects (AE) in patients receiving oral antineoplastic agents. Material and methods: We performed an observational, prospective study of cancer outpatients treated with oral antineoplastic agents (OAA), monitored by the eOncosalud app between August 2017 and October 2021. Safety variables were collected from eOncosalud: the number of AE; severity of the AE according to CTCAE, version 4.03; timelapse from app installation to first recorded AE; automatic recommendations issued; and the patient's acceptance of the recommendations made. To assess the impact of the recommendations generated by the algorithm, we calculated the positive predictive value (PPV) as the number of recommendations accepted out of the total number of recommendations generated. Safety-related patient messages were also analyzed (AE, drug-drug interactions, drug administration). Result: The app was downloaded and used by 186 patients (58.0% women), with a mean age of 59.0 years. A total of 1,368 AE were recorded, the most frequent being fatigue (19.37%), diarrhea (18.20%), and skin changes (9.21%). Regarding the recommendations issued by the app algorithm, 102 patients received 344 information brochures, 39 patients received 51 recommendations for supportive care to control AE, 60 patients received 240 recommendations to visit their primary care doctor, 14 patients received 16 recommendations to contact their specialist pharmacist or oncologist-hematologist, and 34 patients received 73 recommendations to go to the emergency room. The suggestion to go to the emergency room and contact the specialist pharmacist or oncologist-hematologist had a PPV of 0.51 and 0.35, respectively. Half of the patients (50.4%) used the messaging module. A total of 1,668 messages were sent. Of these, 47.8% were related to treatment safety: AE, 22.7%; drug-drug interactions, 20.6%; drug administration, 3.6%; and missing a dose, 1.0%. Conclusions: The eOncosalud app enables close, real-time monitoring of patients treated with OAA. The automatic recommendations through the app's algorithm have optimized available healthcare resources. The app facilitated early detection of AE, thus enabling patients themselves to improve the safety of their treatment.

Implantación y evaluación de un modelo de atención farmacéutica domiciliaria mediante Telefarmacia / Implementation and evaluation of a home pharmaceutical care model through Telepharmacy

Objetivo: Describir el impacto de un modelo de atención farmacéutica especializada que incluye el seguimiento farmacoterapéutico de lospacientes mediante una plataforma de Telefarmacia y la dispensación dela medicación en el domicilio.Método: Estudio descriptivo, retrospectivo, llevado a cabo en un serviciode farmacia de un hospital terciario entre el 23 marzo de 2020 y el 31de diciembre de 2021. Se desarrolló un nuevo modelo de atención farmacéutica para la atención de los pacientes crónicos ambulatorios, queincluye: i) definición de los criterios de selección de los pacientes candidatos a Telefarmacia, ii) estratificación de los pacientes según el nivel deriesgo, iii) definición del seguimiento farmacoterapéutico individualizado,iv) adaptación de la plataforma de apps del servicio de farmacia paragarantizar el seguimiento farmacoterapéutico continuo y la monitorizaciónde los pacientes (e-Oncosalud, e-Midcare y farMcuida), v) implantación deun sistema de citación, y vi) el desarrollo de un módulo informático para lagestión de la dispensación y entrega de la medicación en el domicilio. Elimpacto de este modelo de atención se evaluó mediante el análisis deindicadores de actividad, seguridad, adherencia y calidad percibida. Asimismo, se incluyó un estudio adicional sobre el impacto de la COVID-19 en la accesibilidad de la atención médica y la continuidad de los tratamientos,mediante una encuesta a una muestra aleatoria de 100 pacientes.Resultados: Durante el periodo de estudio, 2.737 pacientes se hanbeneficiado del nuevo modelo de atención farmacéutica a distancia. Elnúmero de consultas de Telefarmacia realizadas fue 7.758. (AU)

Objective: To describe the impact of a Specialized PharmaceuticalCare model that includes pharmacotherapeutic monitoring of patientsthrough an Telepharmacy platform and home medication dispensing.Method: A descriptive and retrospective study conducted in the Pharmacy Service of a tertiary hospital, between 23 March 2020 and31 December 2021. A new pharmaceutical care model for chronicambulatory patients was developed, including: (i) definition of criteria forselecting Telepharmacy candidate patients; (ii) stratification of patients byrisk level; (iii) definition of individualized pharmacotherapeutic monitoring;(iv) adaptation of the Pharmacy Service app platform to ensure continuouspharmacotherapeutic monitoring and patient monitoring (e-Oncohealth,e-Midcare and farMcuida), (v) implementation of an appointment system;and (vi) development of a software module for the management of homemedication delivery. The impact of this pharmaceutical care model wasassessed by analyzing indicators of activity, safety, adherence and perceived quality. Moreover, an additional study on the impact of COVID-19was developed in order to assess the accessibility of medical care andcontinuity of treatment through a survey conducted on a random sampleof 100 patients. Results: During the study period, 2,737 patients benefited from thenew remote pharmaceutical care model. A total of 7,758 Telepharmacyconsultations were performed. Pharmacotherapeutic monitoring prevented 1,043 adverse drug reactions, which affected 10.4% of patients(3.6 adverse drug reactions/patient). Mean adherence to treatment was95.2%. Overall satisfaction with the new model was 9.8/10. (AU)

Cost-utility analysis of venetoclax in combination with obinutuzumab as first-line treatment of chronic lymphocytic leukaemia in Spain.

OBJECTIVE: Venetoclax in combination with obinutuzumab has significantly improved efficacy versus immunochemotherapy (progression-free survival) in patients with chronic lymphocytic leukaemia who have not  received prior treatment. The objective of this study was to evaluate its efficiency in Spain using a cost-utility analysis. METHOD: Using a partitioned-survival analysis model adapted to the Spanish  context and based on three health states (progression-free survival, survival  after progression, and death), a simulation of the evolution of patients who  were candidates for initiating first-line treatment was conducted for a lifetime  time horizon. Venetoclax in combination with obinutuzumab was compared to  the most commonly used therapeutic options for these patients at the time of  study design: chlorambucil in combination with obinutuzumab, ibrutinib,  fludarabine in combination with cyclophosphamide and rituximab, and  bendamustine in combination with rituximab. In order to estimate survival  curves, efficacy data were derived from the CLL14 trial and a network meta- analysis. The  analysis was conducted from the perspective of the Spanish  National Healthcare System and included direct healthcare costs (i.e.  pharmacological costs and their administration), and those associated with the management of the disease and adverse events. The resource use was validated by an expert group. Quality of life data were used to estimate the  quality-adjusted life years obtained for each alternative. A threshold of  €25,000/quality-adjusted life years was used. The robustness of the model was evaluated using deterministic and probabilistic sensitivity analyses. RESULTS: Venetoclax in combination with obinutuzumab was shown to be a  dominant alternative compared to the rest of the treatment alternatives, with a  lower cost per patient (€-67,869 compared to chlorambucil in combination  with obinutuzumab, €-375,952 compared to ibrutinib, €-61,996 compared to  fludarabine in combination with cyclophosphamide and rituximab, and €- 77,398 compared to bendamustine in combination with rituximab). It also had  a greater gain in quality-adjusted life years (0.551 quality-adjusted life years  gained compared to chlorambucil in combination with obinutuzumab and  ibrutinib, 1.639 quality-adjusted life years gained compared to fludarabine in  combination with cyclophosphamide and rituximab, and 1.186 quality-adjusted  life years gained compared to bendamustine in combination with  rituximab). Between 68% and 85% of the simulations performed in the  sensitivity analysis showed that venetoclax in combination with obinutuzumab  had lower costs and more quality-adjusted life years gained. CONCLUSIONS: Venetoclax in combination with obinutuzumab is an efficient and  dominant alternative for treating previously untreated patients with chronic lymphocytic leukaemia compared to the available  alternatives and from the perspective of the Spanish National Health System.

OBJETIVO: Venetoclax en combinación con obinutuzumab ha mostrado frente a  la inmunoquimioterapia mejoras significativas en términos de eficacia (supervivencia libre de progresión) en pacientes con leucemia  infocítica crónica que no han recibido tratamiento previo. El objetivo de este  estudio fue evaluar su eficiencia en España a partir de un análisis de coste- utilidad.Método: A partir de un modelo de análisis de la supervivencia adaptado al  contexto español y basado en tres estados de salud (supervivencia libre de  progresión, supervivencia tras progresión y muerte), se llevó a cabo una  simulación de la evolución de los pacientes candidatos a iniciar una primera  línea de tratamiento para un horizonte temporal de toda la vida. Venetoclax en  combinación con obinutuzumab se comparó frente a las opciones terapéuticas  más utilizadas para estos pacientes en el momento del diseño del estudio:  clorambucilo en combinación con obinutuzumab, ibrutinib, fludarabina en  combinación con ciclofosfamida y rituximab, y bendamustina en combinación  con rituximab. Los datos de eficacia para estimar las curvas de supervivencia  fueron derivados del estudio CLL14 y de un metaanálisis en red. El análisis  consideró la perspectiva del Sistema Nacional de Salud incluyendo los costes  sanitarios directos, en concreto los farmacológicos y su administración, y los  asociados al manejo de la enfermedad y acontecimientos adversos. El uso de  recursos fue validado por un grupo de expertos. Se emplearon datos de calidad  de vida para estimar los años de vida ajustados por calidad obtenidos  para cada alternativa. Se consideró un umbral de 25.000 €/años de vida  ajustados por calidad. La robustez del modelo se evaluó mediante análisis de  sensibilidad determinísticos y probabilísticos. RESULTADOS: Venetoclax en combinación con obinutuzumab se mostró como  una alternativa dominante frente al resto de alternativas de tratamiento, con  un menor coste por paciente (­67.869 € frente a clorambucilo en combinación  con obinutuzumab, ­375.952 € frente a ibrutinib, ­61.996 € frente a  ludarabina en combinación con ciclofosfamida y rituximab, y ­77.398 € frente  a bendamustina en combinación con rituximab) y una mayor ganancia en años  de vida ajustados por calidad (0,551 años de vida ajustados por calidad  ganados frente a clorambucilo en combinación con obinutuzumab e ibrutinib,  1,639 años de vida ajustados por calidad ganados frente a fludarabina en  combinación con ciclofosfamida y rituximab, y 1,186 años de vida ajustados  por calidad ganados frente a bendamustina en combinación con rituximab).  Entre el 68% y el 85% de las simulaciones realizadas en el análisis de  sensibilidad mostraban a venetoclax en combinación con obinutuzumab con un  menor coste y un mayor número de años de vida ajustados por calidad  ganados. CONCLUSIONES: Venetoclax en combinación con obinutuzumab se muestra como una alternativa eficiente y dominante como tratamiento de  pacientes con leucemia linfocítica crónica no tratados previamente frente a las  alternativas disponibles y desde la perspectiva del Sistema Nacional de Salud.

Patient-reported outcomes and mobile applications. A review of their impact on patients' health outcomes.

OBJECTIVE: To review the evidence of the mobile apps in collection patient- reported outcomes and their impact on health outcomes. Method: A review was conducted of the literature on apps aimed at collecting  patient-reported outcomes. Selected articles were required to consider the  apps' impact on patients' health outcomes. The search was carried out during  April 2021 in Pubmed and Embase using the search terms "app", "mobile  applications" , "patient-reported outcomes", "outcome assessment, health  care", and "quality of life", To be included articles had to be written in English  or Spanish and they were required to dwell on apps used by patients, family  members and/or caregivers that measured at least one health outcome. No  time restrictions were applied. RESULTS: Of the 26 articles reviewed, 19 (73.1%) were clinical trials, 4  (15.4%) were quasi-experimental studies, and 3 (11.5%) were observational studies. A pharmacy department was involved in 4 studies  (15.4%), and 3 (11.5%), were carried out in Spain. The sample size ranged  from 14 to 411. Depending on the study population, the most frequent studies included cancer patients (42.3%) and patients with cardiovascular  diseases (26.9%). Most of the studies focused on measuring the impact of the app on the patients' quality of life (50.0%), control of clinical parameters  (46.2%), adherence (38.5%), and management of symptoms and/or reduction  of complications (26.9%). Overall efficacy in terms of the  percentage of studies where apps were found to result in a significant  improvement was 73.1%. The most heavily impacted patient-reported  outcomes were adherence, health-related quality of life and satisfaction. CONCLUSIONS: There is emerging evidence that apps have a positive impact on  patients' health outcomes. These tools have shown to lead to an improvement  in the management of different conditions, with results showing a reduction in  complications rates and in the consumption of resources as well as better  adherence to medication and enhanced patient quality of life.

OBJETIVO: Realizar una revisión sobre la evidencia de las aplicaciones móviles  en el registro de los patient-reported outcomes y su impacto en los resultados  en salud.Método: Revisión de la literatura sobre los estudios de aplicaciones orientadas  al registro de patient-reported outcomes y que analizaran su impacto en los  resultados en salud de los pacientes. La búsqueda se realizó en abril de 2021  en Pubmed y Embase con los términos "App", "Mobile Applications"; "Patient  Reported Outcomes"; "Outcome Assessment, Health Care"; "Quality of Life". Se  incluyeron artículos publicados en inglés o español sin límite de tiempo y  que incluyeran aplicaciones cuyos participantes fueran pacientes, familiares y/o  cuidadores y que midieran algún tipo de resultado en salud. RESULTADOS: De los 26 artículos revisados, 19 (73,1%) fueron ensayos clínicos, 4 (15,4%) estudios cuasiexperimentales y 3 (11,5%) estudios  observacionales. En 4 estudios (15,4%) estaba implicado un servicio  de farmacia y en 3 (11,5%) el estudio fue realizado en España. El tamaño  muestral varió de 14 a 411. En función de la población de estudio, los más  frecuentes incluyeron pacientes oncológicos (11 [42,3%] estudios) y pacientes  con patologías cardiovasculares (7 [26,9%] estudios). La mayoría de los  estudios se centraron en la medición del impacto de las aplicaciones en  términos de calidad de vida (50,0%), control de parámetros clínicos (46,2%),  adherencia (38,5%) y manejo de los síntomas y/o reducción de complicaciones (26,9%). La eficacia global en términos del porcentaje en los que se observó una mejoría significativa con el uso de las aplicaciones fue del 73,1%. Los patient-reported outcomes en los que se observó un mayor impacto fueron la adherencia, la calidad de vida relacionada con la salud y la satisfacción. CONCLUSIONES: Existe evidencia emergente de que las aplicaciones tienen un  impacto positivo en los resultados en salud de los pacientes. Estas herramientas están demostrando una mejora en el manejo de diferentes patologías, con resultados que muestran una reducción de  complicaciones y consumo de recursos y mejoras en la adherencia y calidad de  vida de los pacientes.

Implementation of a methodology to assess patient reported outcomes in lung cancer patients: The PeOpLe (Patient-reported Outcomes in Lung cancer ) study protocol.

OBJECTIVE: The purpose of this article is to describe the PeOpLe study protocol, developed to assess patient-reported health outcomes in  advanced or metastatic non-small-cell lung cancer in routine clinical practice using the methodology provided by the International Consortium for Health Outcomes Measurement tool. METHOD: The study envisaged will be multicenter, longitudinal, ambispective and observational. Two groups will be compared: a control group (followed up according to standard clinical practice) and an experimental group (followed up using the International Consortium for Health  Outcomes Measurement methodology adapted to the Spanish setting for 6  months). The variables collected will be related to demography (age, sex,  degree of family support), clinical factors (smoking, comorbidities, lung  capacity), the neoplasm (histology, staging, mutations), pharmacotherapy  (treatment schedule, modifications, and complications), health status  (functional status, quality of life, satisfaction and overall survival) and resource consumption (emergency visits, hospital admissions and time spent by health providers). The PeOpLe study protocol has been approved by the Ethics Committee for Research into Medicinal Products of the Gregorio Marañón General University Hospital and will be conducted in compliance with prevailing ethical principles and standards. CONCLUSIONS: The PeOpLe study will explore how patient-reported outcomes collection can be developed and integrated with the clinical processes used in  the management of patients with locally advanced or metastatic nonsmall cell  lung cancer what patient-reported outcomes can be measured with systems  that can conveniently be used both by patients and by healthcare providers.  Systematic evaluation of patient-reported outcomes will help determine their  impact in terms of effectiveness (survival), safety (complications of systemic  therapy), and quality of life and patient satisfaction. The multidisciplinary and  multicenter nature of the study will facilitate a comprehensive view of the  subject analyzed and allow external reproducibility.

OBJETIVO: El objetivo es describir el protocolo del estudio PeOpLe, cuyo fin es  evaluar los resultados en salud centrados en el paciente con cáncer de pulmón  no microcítico avanzado o metastásico en la práctica clínica habitual mediante  una metodología adaptada de la herramienta del International Consortium for  Health Outcomes Measurement.Método: Estudio observacional, ambispectivo, longitudinal y multicéntrico. Se  compararán dos grupos: grupo control (seguimiento según práctica clínica  habitual) frente a un grupo intervención (seguimiento mediante la metodología  del International Consortium for Health Outcomes Measurement adaptada al entorno español) durante un período de 6 meses.  Las variables recogidas incluirán aspectos demográficos (edad, sexo, apoyo familiar), clínicos (hábito tabáquico, comorbilidades, capacidad   pulmonar), del tumor (histología, estadiaje, mutaciones), farmacoterapéutico (esquema de tratamiento, modificaciones y  complicaciones), grado de salud (estado funcional, calidad de vida, satisfacción y supervivencia global) y consumo de recursos (visitas a urgencias, ingresos  hospitalarios y tiempo dedicado por los profesionales sanitarios). El protocolo  del estudio PeOpLe ha sido aprobado por el Comité de Ética de la Investigación con medicamentos y se realizará respetando los principios y las normas éticas  básicas. CONCLUSIONES: El estudio PeOpLe explorará cómo se pueden desarrollar e  integrar los procesos de medición de resultados en salud centrados en los  pacientes, especialmente los patient-reported outcomes, en pacientes con  cáncer de pulmón no microcítico localmente avanzado o metastásico en la  práctica clínica. La evaluación sistemática de estos patient-reported outcomes  permitirá conocer su impacto en términos de efectividad (supervivencia),  seguridad (complicaciones de la terapia sistémica) y calidad de vida y  satisfacción. El carácter multidisciplinar y multicéntrico facilitará una visión  integral y su reproducibilidad externa.

Information and Communication Technologies in Patients With Immune-Mediated Inflammatory Diseases: Cross-sectional Survey.

BACKGROUND: Information and communication technologies (ICTs) are changing the traditional health care model and redefining personalized health. ICTs offer effective communication and real-time monitoring of patients and provide additional data to support clinical decision-making, improve the quality of care, and contribute to the empowerment of patients. However, evidence on the use of ICTs and digital preferences of immune-mediated inflammatory disease (IMID) patients is scarce. OBJECTIVE: The aim of this study is to describe the degree of use of ICTs in patients with IMIDs (including rheumatic diseases, inflammatory bowel diseases, and psoriasis), identify their needs, and analyze their interest in the use of apps as tools for better management of their disease. METHODS: A questionnaire was created by a multidisciplinary team including pharmacists, rheumatologists, gastroenterologists, dermatologists, and nurses with experience in ICTs applied to the field of IMID. The survey included 27 questions organized into 3 blocks: (1) sociodemographic characteristics, (2) ICT use for health-related information, and (3) patient expectations about mobile health. RESULTS: A total of 472 questionnaires were analyzed. Overall, 52.9% (250/472) of patients were diagnosed with a rheumatologic disease, 39.4% (186/472) with inflammatory bowel disease, and 12.3% (58/472) with psoriasis. The state of health was considered good by 45.6% (215/472) of patients. Patients were interested in staying informed about health issues in 86.9% (410/427) of cases and sought health-related information mainly from the internet (334/472, 70.8%) and health care professionals (318/472, 67.4%). Overall, 13.6% (64/472) did not trust the health information they found in internet. Of the patients, 42.8% (202/472) had a health app, and 42.2% (199/472) had found it on their own. Patients would like a health app to help mainly to manage appointments (281/472, 59.5%), obtain information about their diseases and treatments (274/472, 58.1%), and get in contact with health professionals (250/472, 53.0%). Overall, 90.0% (425/472) of patients reported they would use an app to manage their IMID if their health professional recommended it, and 58.0% (274/472) would pay or probably be willing to pay for it. CONCLUSIONS: IMID patients were very interested in finding health-related information via ICTs, especially using smartphones and apps recommended by health professionals. Appointment management, advice on disease and treatment management, and personalized communication with health professionals were the most desired app features identified. Health professionals should play an essential role in recommending and validating these tools to ensure they are of high quality.

Smartphone-Based Ecological Momentary Assessment for the Measurement of the Performance Status and Health-Related Quality of Life in Cancer Patients Under Systemic Anticancer Therapies: Development and Acceptability of a Mobile App.

Background: We have defined a project to develop a mobile app that continually records smartphone parameters which may help define the Eastern Cooperative Oncology Group performance status (ECOG-PS) and the health-related quality of life (HRQoL), without interaction with patients or professionals. This project is divided into 3 phases. Here we describe phase 1. The objective of this phase was to develop the app and assess its usability concerning patient characteristics, acceptability, and satisfaction. Methods: The app eB2-ECOG was developed and installed in the smartphone of cancer patients who will be followed for six months. Criteria inclusion were: age over 18-year-old; diagnosed with unresectable or metastatic lung cancer, gastrointestinal stromal tumor, sarcoma, or head and neck cancer; under systemic anticancer therapies; and possession of a Smartphone. The app will collect passive and active data from the patients while healthcare professionals will evaluate the ECOG-PS and HRQoL through conventional tools. Acceptability was assessed during the follow-up. Patients answered a satisfaction survey in the app between 3-6 months from their inclusion. Results: The app developed provides a system for continuously collecting, merging, and processing data related to patient's health and physical activity. It provides a transparent capture service based on all the available data of a patient. Currently, 106 patients have been recruited. A total of 36 patients were excluded, most of them (21/36) due to technological reasons. We assessed 69 patients (53 lung cancer, 8 gastrointestinal stromal tumors, 5 sarcomas, and 3 head and neck cancer). Concerning app satisfaction, 70.4% (20/27) of patients found the app intuitive and easy to use, and 51.9% (17/27) of them said that the app helped them to improve and handle their problems better. Overall, 17 out of 27 patients [62.9%] were satisfied with the app, and 14 of them [51.8%] would recommend the app to other patients. Conclusions: We observed that the app's acceptability and satisfaction were good, which is essential for the continuity of the project. In the subsequent phases, we will develop predictive models based on the collected information during this phase. We will validate the method and analyze the sensitivity of the automated results.

Evaluation of the hospital care quality perceived by patients with immune-mediated inflammatory diseases from the pharmacy service. SACVINFA study.

WHAT IS KNOWN AND OBJECTIVE: Immune-mediated inflammatory diseases (IMIDs) are a group of chronic and highly disabling diseases. The objective is to evaluate the satisfaction with the health care received by patients with the most prevalent IMIDs in Spain: inflammatory bowel disease (IBD), psoriasis (Ps) psoriatic arthritis (PsA), rheumatoid arthritis (RA) and spondyloarthropathies (SpAs), and to determine the factors that influence patient satisfaction. METHODS: This was an observational, cross-sectional, multicentre study in a real-world evidence context conducted in the Pharmacy Service in four hospital centres of the Community of Madrid that belong to the National Health System. The study included adult patients diagnosed with an IMID who had attended the Pharmacy Service at least three times. The patients were grouped according to the main IMID. Health care satisfaction was evaluated using the chronic patient experience assessment (IEXPAC) questionnaire. The responses to IEXPAC are grouped into three factors: productive interactions, new relational model and patient self-management, with a total score from 0 (worst) to 10 (best experience). Health-related quality of life (HRQoL) was also evaluated using the EQ-5D-5L questionnaire, and pharmacological adherence was evaluated through the Morisky-Green test. RESULTS AND DISCUSSION: A total of 578 patients were analysed (IBD = 25.3%; Ps = 19.7%; SpAs = 18.7%; RA = 18.5%; PsA = 17.8%). The mean age (SD) was 49.8 (12.3) years and 50.7% were male. The average score (SD) for the total IEXPAC sample was 6.6 (1.9). RA was the IMID with the lowest score, at 5.83 (2.0), significantly lower than the scores of Ps (SD) [7.01 (1.7); p = 0.003], IBD [6.83 (1, 9); p = 0.012] and SpAs [6.80 (1.6); p = 0.001]. Productive interactions (SD) [8.5 (1.8)] and patient self-management (SD) [7.3 (2.3)] were the factors with the highest scores, and the new relational model had the lowest score (SD) [3.2 (2.7)]. Male gender, a longer time interval between medication administrations and a higher HRQoL were correlated with better patient satisfaction. Current biological therapy (according to the Anatomical Chemical classification system) also had a significant influence; patients treated with tumour necrosis factor inhibitors and interleukin inhibitors showed greater satisfaction than those treated with selective immunosuppressants. WHAT IS NEW AND CONCLUSION: The IEXPAC results show high general satisfaction with care quality reported by patients with IMIDs treated in the Pharmacy Service. However, there are areas of improvement in care quality specially health professional-patient communication, such as increasing access to information, and promoting and facilitating relationships with patients in similar conditions.

Design and implementation of a mobile app for the pharmacotherapeutic follow-up of patients diagnosed with immune-mediated inflammatory diseases: eMidCare.

Background: Pharmacotherapeutic management of immune-mediated inflammatory diseases (IMID) has become more complex due to the development of new treatments, such as biological therapies. Mobile health, especially apps, can provide IMID patients with greater autonomy and facilitate communication with healthcare professionals. Our objective was to design and implement an app for remote monitoring and communication with IMID patients. Methods: A multidisciplinary group was created to design and develop an app for IMID patients in a tertiary hospital. The app functionalities were identified through a focus group with IMID patients and through an observational, descriptive study of available apps for IMID patients at App Store and Play Store platforms. Once the app was designed and developed, we offered the app to IMID patients who initiated a new biological therapy. The inclusion period was from December 2020 to August 2021. We performed an observational, longitudinal study to assess the app's impact on medication safety, communication, satisfaction, and usability. Results: We designed an app (eMidCare®) with the following modules: My Medication, My Questionnaires, Adverse Events, Useful Information, Messages, and Patient Profile. A total of 85 patients were installed with the app. The median (range) follow-up time for app use was 123 (5-270) days. In the My Medication module, 100% of patients registered their biological therapy and 25.9% also used this module to record each dose of medication administered. A total of 82 adverse events (AEs) were registered. Thirty-two percent of the patients registered at least 1 AE. The most frequent AEs were fatigue, injection site reaction, headache, and nausea. Fifty-two percent of patients used the Messages module to communicate with healthcare professionals. The most frequent messages concerned doubts about managing AEs (26.2%) and drug interactions (18.9%). The satisfaction survey yielded a median (range) score of 9.1 (7-10) out of 10. Conclusions: We developed an app, eMidCare®, which reminds patients to take their medication, enables them to record AEs, and helps them communicate with healthcare professionals. Approximately one-third of the patients registered the administration of the biological therapies and registered at least 1 AE. The most used and most satisfactory functionality was communication with health professionals.

Implantación de una metodología para evaluarpatient-reported outcomes en pacientes con cáncer de pulmón: Protocolo del estudio PeOpLe(Patient-reported Outcomes in Lung cancer) / Implementation of a methodology to assess patient reported outcomes in lung cancer patients: The PeOpLe (Patient-reported Outcomes in Lung cancer) study protocol

Objetivo: El objetivo es describir el protocolo del estudio PeOpLe, cuyofin es evaluar los resultados en salud centrados en el paciente con cáncerde pulmón no microcítico avanzado o metastásico en la práctica clínicahabitual mediante una metodología adaptada de la herramienta del International Consortium for Health Outcomes Measurement.Método: Estudio observacional, ambispectivo, longitudinal y multicéntrico. Se compararán dos grupos: grupo control (seguimiento según práctica clínica habitual) frente a un grupo intervención (seguimiento mediantela metodología del International Consortium for Health Outcomes Measurement adaptada al entorno español) durante un período de 6 meses. Lasvariables recogidas incluirán aspectos demográficos (edad, sexo, apoyofamiliar), clínicos (hábito tabáquico, comorbilidades, capacidad pulmonar), del tumor (histología, estadiaje, mutaciones), farmacoterapéutico(esquema de tratamiento, modificaciones y complicaciones), grado desalud (estado funcional, calidad de vida, satisfacción y supervivencia global) y consumo de recursos (visitas a urgencias, ingresos hospitalariosy tiempo dedicado por los profesionales sanitarios). El protocolo del estudio PeOpLe ha sido aprobado por el Comité de Ética de la Investigacióncon medicamentos y se realizará respetando los principios y las normaséticas básicas. (AU)

Objective: The purpose of this article is to describe the PeOpLe studyprotocol, developed to assess patient-reported health outcomes in advanced or metastatic non-small-cell lung cancer in routine clinical practiceusing the methodology provided by the International Consortium forHealth Outcomes Measurement tool.Method: The study envisaged will be multicenter, longitudinal, ambispective and observational. Two groups will be compared: a control group(followed up according to standard clinical practice) and an experimentalgroup (followed up using the International Consortium for Health OutcomesMeasurement methodology adapted to the Spanish setting for 6 months).The variables collected will be related to demography (age, sex, degreeof family support), clinical factors (smoking, comorbidities, lung capacity),the neoplasm (histology, staging, mutations), pharmacotherapy (treatmentschedule, modifications, and complications), health status (functionalstatus, quality of life, satisfaction and overall survival) and resource consumption (emergency visits, hospital admissions and time spent by healthproviders). The PeOpLe study protocol has been approved by the EthicsCommittee for Research into Medicinal Products of the Gregorio MarañónGeneral University Hospital and will be conducted in compliance withprevailing ethical principles and standards. (AU)

Defining a Standard Set of Patient-Reported Outcomes for Patients With Advanced Ovarian Cancer.

Purpose: Advanced ovarian cancer (AOC) and its treatment cause several symptoms and impact on patients' health-related quality of life (HRQoL). We aim to reach a consensus on the most relevant patient-reported outcome (PROs), the corresponding measures (PROMs), and measurement frequency during AOC patients' follow-up from patients' and healthcare professionals' (HCP) perspective. Methods: The project comprised five steps: 1) a literature review, 2) a focus group with patients, 3) a nominal group with HCP, 4) two round-Delphi consultations with patients and HCP, and 5) a final meeting with HCP. Delphi questionnaire was elaborated based on literature review, focus group (n=5 patients), and nominal group (n=16 HCP). The relevance of each PRO and the appropriateness (A) and feasibility (F) of the proposed PROM were assessed (Likert scale 1=strongly agree; 9=strongly disagree). The consensus was reached when at least 75% of the panelists rated it as 'relevant', 'appropriate', or 'feasible' (score 7-9). Results: A total of 56 HCP [51.8% Hospital Pharmacy; 41.1% Oncology; 3.6% Nursing; and 3.6% Psycho-oncology; mean time in specialty 12.5 (8.0) years] and 10 AOC patients [mean time diagnosis 5.4 (3.0) years] participated in the 1st round. All PROs achieved consensus regarding their relevance, except dry skin (58.0%). Agreement was reached for PRO-CTCAE to be used to assess fatigue (A:84.9%; F:75.8%), neuropathy (A:92.4%; F:77.3%), diarrhea (A:87.9%; F:88.7%), constipation (A:86.4%; F:75.8%), nausea (A:89.4%; F:75.8%), insomnia (A:81.8%; F:88.7%), abdominal bloating (A:82.2%; F:82.2%) and sexuality (A:78.8%; F:88.6%); EQ-5D to determine patients' HRQoL (A:87.9%; F:80.3%), pain (A:87.9%; F:75.8%) and mood (A:77.7%; F:85.5%); to assess treatment adherence the Morisky-Green (A:90.9%; F:84.9%) and the dispensing register (A:80.3%; F:80.3%) were chosen. It was agreed to note in the medical record whether the patient's treatment preferences had been considered during decision-making (A:78.8%; F:78.8%) and to use a 5-point Likert scale to assess treatment satisfaction (A:86.4%; F:86.4%). Panelists agreed (A:92.4%; F: 77.3%) to collect these PROs (1) at the time of diagnosis/relapse; (2) one month after starting treatment/change therapeutic strategy; (3) every three months during the 1st-year of treatment; and later (4) every six months until treatment completion/change. Conclusions: The consensus reached represents the first step towards including the patient's perspective in AOC follow-up. The standardized collection of PROs in clinical practice may contribute to optimizing the follow-up of these patients and thus improving the quality of care.

A New Methodology to Estimate Drug Cost Avoidance in Clinical Trials: Development and Application.

Background: Oncology clinical trials can lead to relevant financial savings in drug acquisition for healthcare providers. Considerable methodological heterogeneity is observed among previous studies estimating these savings. Methods: We developed a methodology to estimate the economic benefit obtained from the enrollment of patients into clinical trials through the analysis of drug cost avoidance. We designed a decision algorithm to determine if a clinical trial is associated with drug cost avoidance. This algorithm is based on five scenarios according to the availability or not of standard treatment, the presence or absence of a control arm (placebo or active treatment), and the provider of the medication. We considered as reference the cost of the standard treatment that the patient would have received in routine clinical practice. We standardized drug doses and treatment durations according to the literature. Costs were considered from a National Health System perspective. We applied this methodology at a single, research-active University Hospital in 2019. A cost avoidance analysis per trial and patient was carried out on cancer patients. Results: We analyzed 140 trials in which 198 patients were recruited. Drug cost avoidance was found in 120 trials (85.7%). The estimated total drug cost avoidance amounted to over €3,200,000. Melanoma and genitourinary tumors were the tumor types associated with the highest cost avoidance. The average drug cost avoidance per patient was €16,245. Conclusion: We describe a standardized method to estimate drug cost avoidance in clinical trials. We have applied it to all ongoing oncology clinical trials in our center. This methodology could be valuable for other centers to analyze the potential saving of clinical trials.

Análisis coste-utilidad de venetoclaxen combinación con obinutuzumab comotratamiento de primera línea de la leucemia linfocítica crónica en España / Cost-utility analysis of venetoclax in combination with obinutuzumab as first-line treatment of chronic lymphocytic leukaemia in Spain

Objetivo: Venetoclax en combinación con obinutuzumab ha mostradofrente a la inmunoquimioterapia mejoras significativas en términos de eficacia(supervivencia libre de progresión) en pacientes con leucemia linfocíticacrónica que no han recibido tratamiento previo. El objetivo de este estudiofue evaluar su eficiencia en España a partir de un análisis de coste-utilidad.Método: A partir de un modelo de análisis de la supervivencia adaptadoal contexto español y basado en tres estados de salud (supervivencia librede progresión, supervivencia tras progresión y muerte), se llevó a cabouna simulación de la evolución de los pacientes candidatos a iniciar unaprimera línea de tratamiento para un horizonte temporal de toda la vida. Venetoclax en combinación con obinutuzumab se comparó frente a lasopciones terapéuticas más utilizadas para estos pacientes en el momentodel diseño del estudio: clorambucilo en combinación con binutuzumab,ibrutinib, fludarabina en combinación con ciclofosfamida y rituximab, ybendamustina en combinación con rituximab. Los datos de eficacia paraestimar las curvas de supervivencia fueron derivados del estudio CLL14 y de un metaanálisis en red. El análisis consideró la perspectiva del Sistema Nacional de Salud incluyendo los costes sanitarios directos, en concreto losfarmacológicos y su administración, y los asociados al manejo de la enfermedady acontecimientos adversos. El uso de recursos fue validado por ungrupo de expertos. Se emplearon datos de calidad de vida para estimarlos años de vida ajustados por calidad obtenidos para cada alternativa.Se consideró un umbral de 25.000 €/años de vida ajustados por calidad. La robustez del modelo se evaluó mediante análisis de sensibilidad determinísticosy probabilísticos.

Objective: Venetoclax in combination with obinutuzumab has significantlyimproved efficacy versus immunochemotherapy (progression-freesurvival) in patients with chronic lymphocytic leukaemia who have notreceived prior treatment. The objective of this study was to evaluate itsefficiency in Spain using a cost-utility analysis.Method: Using a partitioned-survival analysis model adapted to theSpanish context and based on three health states (progression-free urvival,survival after progression, and death), a simulation of the evolutionof patients who were candidates for initiating first-line treatment wasconducted for a lifetime time horizon. Venetoclax in combination withobinutuzumab was compared to the most commonly used therapeuticoptions for these patients at the time of study design: chlorambucil incombination with obinutuzumab, ibrutinib, fludarabine in combinationwith cyclophosphamide and rituximab, and bendamustine in combinationwith rituximab. In order to estimate survival curves, efficacy datawere derived from the CLL14 trial and a network meta-analysis. The analysis was conducted from the perspective of the Spanish NationalHealthcare System and included direct healthcare costs (i.e. pharmacologicalcosts and their administration), and those associated with themanagement of the disease and adverse events. The resource use wasvalidated by an expert group. Quality of life data were used to estimatethe quality-adjusted life years obtained for each alternative. A thresholdof €25,000/quality-adjusted life years was used. The robustness of themodel was evaluated using deterministic and probabilistic sensitivityanalyses.