Oral Communications

Abstract

#44

Late adverse events in patients treated with CAR T-cell for aggressive B-cell non-Hodgkin Lymphoma: A prospective, multicentre, real-world study

L. Camacho-Arteaga^1,2, G. Iacoboni^1,3, M. Kwon^4,5,6, R. Hernani^7,8, L. López-Corral^9,10, L. M. Leguízamo-Martínez^11,12,13, M. Guerreiro¹⁴, C. Alonso-Martínez¹, P. Barba^1,3,2 and A. Agustí^1,2

¹Hospital Universitari Vall d'Hebron, Barcelona, Spain; ²Universitat Autònoma de Barcelona, Barcelona, Spain; ³Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; ⁴Hospital General Universitario Gregorio Marañón, Madrid, Spain; ⁵Institute of Health Resarch Gregorio Marañón, Madrid, Spain; ⁶Universidad Complutense de Madrid, Madrid, Spain; ⁷Hospital Clínico Universitario, Valencia, Spain; ⁸INCLIVA Research Institute, Valencia, Spain; ⁹Hospital Universitario de Salamanca, IBSAL, CIBERONC, Salamanca, Spain; ¹⁰Centro de Investigación del Cáncer-IBMCC (USAL-CSIC), Salamanca, Spain; ¹¹Hospital Clinic of Barcelona, Barcelona, Spain; ¹²Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; ¹³Universitat de Barcelona, Barcelona, Spain; ¹⁴Hospital Universitari i Politecnic La Fe, Valencia, Spain

Objective: Acute adverse events after CAR T-cell infusion are well known, but less information is available about long-term toxicities and their incidence. Our research aimed to describe the occurrence of any late adverse event (AE) in patients with an aggressive B-cell non-Hodgkin lymphoma (NHL) treated with CD19 CAR-T cells.

Material and/or methods: A prospective, observational study was carried out in six Spanish centres from 1 September 2018 to 31 December 2022. All adult patients diagnosed with an aggressive B-cell NHL treated with a commercial CAR T-cell product (tisagenlecleucel or axicabtagene ciloleucel) who had not received any other treatment for their disease at 3 months post-infusion were included. Late AEs were defined as those that either persisted or occurred beyond 3 months post-infusion. Incidence and severity of late AE episodes were analysed.

Results: A total of 172 infused patients were evaluated with a median follow-up of 13.9 months (IQR8.2–23.8). One hundred thirty-five (78.5%) patients experienced at least one late AE of any grade, being infection episodes with an incidence of 5.63 per 100 person-months, [CI 95% 4.50–7.04], the most frequent, followed by neutropenia (3.59 per 100 person-months [CI 95% 2.89–4.53]) and thrombocytopenia (2.24 per 100 person-months [CI 95% 1.65–3.02]). There were no differences in the late AEs incidence between the constructs. Five neoplasms in four (2.3%) patients were reported with no cases of T-cell malignancies. Other AEs were mild dermatological AEs. Paresthesias and heart failure were the most frequent neurological and cardiovascular AEs, respectively. Cumulative incidence of NRM at 24 months was 6.3%, with main cause infections in seven (4.0%) patients (three because of COVID-19 pneumonia and four due to either sepsis or bacterial pneumonia).

Conclusions: Late AEs are frequent after CAR T-cell therapy with infections and cytopenias being the most frequent events. The frequency of secondary malignancies was low, and no cases of T-cell malignancies were described.

#60

Automated detection and prevention of adverse drug reactions: Preliminary results

E. Montané Esteva^1,2, P. Novales Herbera¹, G. De La Rosa Loppacher¹, A. Cia Hidalgo³, S. Videla Ces¹, O. Hladun Alvaro¹, M. Farré Albaladejo^1,2 and J. M. Mòdol Deltell^4,5

¹Department of Clinical Pharmacology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; ²Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain; ³Hospital Information System, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; ⁴Department of Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; ⁵Department of Medicine, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Spain

Objective: To evaluate the implementation of automated systems (clinical maps) that detect hospitalized patients with ADRs and/or at risk of developing an ADR in hospital clinical practice.

Results: (a) Sub-study 1: The prevalence among patients admitted to the hospital and the approximate number of cases detected per month of each ADR were 0.07% (95% CI: 0.03%–0.18%) for PCA (two cases), 0.21% (95% CI: 0.13%–0.35%) for BAT (five cases), 0.25% (95% CI: 0.16%–0.41%) for HGC (six cases) and 0.57% (95% CI: 0.42%–0.78%) for IIS (13 cases). (b) Sub-study 2: 18 patients with risks between 16 and 20 points were analysed, all had kidney failure (KF), and the median prescribed drugs was 23 (12–26). Actions to modify their medication plan were agreed upon in seven patients (39%, 95% CI: 20.3%–61.4%), which were monitoring parameter (40%), dose adjustment for KF (30%) and drug withdrawal (20%). The most frequent involved drugs were antithrombotics (40%) and antibiotics (20%). In addition, in one patient, the allergy label was removed, and another patient resulted in a revised care protocol.

Conclusions: The automation of the pharmacovigilance processes is useful to obtain prevalence data of specific suspected ADRs and to increase the safety of inpatients. In addition, it allows defining effective hospital policy strategies.

#62

Hospital admissions due to acute drug poisoning: A descriptive study from the Minimum Basic Data Set of Hospital Discharges database

D. Wang^1,2, C. Aguilera Martin¹, L. Camacho Arteaga^1,2, R. Muñoz Gallarín¹ and I. Danés Carreras^1,2

¹Hospital Universitario Vall d'Hebron, Barcelona, Spain; ²Universitat Autònoma de Barcelona, Barcelona, Spain

Objective: The study aims to describe the profile of patients admitted to Vall d'Hebron University Hospital for acute drug poisoning.

Material and/or methods: A descriptive, retrospective study was performed at the Vall d'Hebron University Hospital with data registered on Minimum Basic Data Set of Hospital Discharges (CMBD-AH) database. Patients admitted with acute poisoning (AP) diagnoses (T36-T50 ICD-10 codes) between 2018 and 2022 were identified. Sociodemographic and clinical characteristics of patients, drugs/substances involved in AP and outcomes were described. The data were analysed using RStudio and Excel programs.

Results: A total of 1789 patients with 2098 episodes of AP diagnosis were identified. Median age of patients was 51 years (IQR 28–70), and 56.8% were female. Two hundred and three patients (11.3%) had more than one episode of AP. The median length of hospital stay was 1 day (IQR 1–4). The majority of discharges with AP were from psychiatry (689; 32.8%) and adult emergency departments (586; 27.9%). The most common AP was due to benzodiazepines (574 episodes [417 were self-poisoning]), followed by 4-aminophenol derivatives (117 episodes [102 self-poisoning]) and antipsychotics and neuroleptics (111 episodes [71 self-poisoning]). Regarding the severity, 198 episodes (9.4%) required intensive care unit assistance, with a median length of stay of 3 days (IQR 2–7). Sixty-three patients died (3%), being poisoning the main cause of death in 13.

Conclusions: AP episodes were mainly due to benzodiazepines, 4-aminophenol derivatives and antipsychotics and neuroleptics, most of which were cases of self-poisoning. Around one out of 10 episodes required intensive care unit assistance. Less than 1% of patients died due to AP.

#78

Understanding complexities: Real-world data analysis of patients affected by multiple adverse drug reactions

A. Alonso, V. Aniyar, E. Guillen, M. Calvo and J. Saez

Hospital Clinic Barcelona, Barcelona, Spain

Objective: The aim of this study was to perform a descriptive characterization of a patient cohort with multiple ADRs in a high-complexity tertiary hospital.

Material and/or methods: The study was approved by the Hospital Clinic Barcelona (HCB) Drug Research Ethics Committee. All medical records of patients with an ADR notification from 2017 to February 2024 on the HCB Pharmacovigilance Program were reviewed, and those with at least a second ADR recorded were selected. Variables collected were sex, age, drug ATC codes, type of reaction (if the patient had more than two ADRs, only the first two types were collected), severity (defined by CTCAE v5.0) and comorbidities.

Results: Six hundred fifty-five patients with at least one ADR notification in HCB were identified, of which 142 (21.6%) patients had at least a second ADR. From those 142 patients, 91 were females (64.1%), with a median age of 69 (IQR: 35 min 21, max 94), and 33 patients (23.3%) had three or more ADRs. Most prevalent comorbidities were arterial hypertension (65, 45.7%), neoplasms (61, 42.9%) and dyslipidaemia (34, 23.9%). Only 9 patients (6.3%) did not have any comorbidity. In the 284 reactions analysed (two ADRs per patients), the most common drug ATC codes involved were anti-infectives for systemic use (110, 38.4%), antineoplastic and immunomodulating agents (60, 21.1%) and various (30, 10.5%). The most prevalent type of ADRs were allergic (163, 57.3%); dermatological (64, 22.5%), mostly reported as toxicoderma (25/64, 39%); haematological (11, 3.87%), mostly consisting in cytopenia (8/11, 81.8%); and pulmonary (11, 3.87%), with drug-induced pneumonitis (10/11, 90.9%).

Conclusions: Almost a quarter of patients with one ADR presented at least a second ADR. Almost all of them had comorbidities, being hypertension and neoplasms the most prevalent. Most were elderly women, in line with previous studies, which highlights the impact of age and sex in ADR generation.

#100

Data quality in multi-database pharmacoepidemiologic studies: A step towards trustworthy real-world evidence

J. Riera Arnau^1,2, N. Del Peso Casado¹, C. Andaur Navarro², V. Hoxhaj², M. Sturkenboom², O. Klungel³ and S. Abtahi³

¹Hospital Universitari Vall d'Hebron, Barcelona, Spain; ²University Medical Centre of Utrecht, Utrecht, Netherlands; ³Utrecht University, Utrecht, Netherlands

Objective: Multi-database pharmacoepidemiology studies (MDPES) are vital for clinical pharmacology decision-making. Various initiatives aim to standardize and verify data quality (DQ), yet challenges persist due to inconsistent DQ definitions and assessment methods in the literature. This study aims to evaluate current DQ assessment and reporting in MDPES.

Material and/or methods: We searched PubMed from September-2016 (after the seminal DQ framework by Kahn) to July 2023. We included observational pharmacoepidemiology studies (drug utilization or outcome studies) using ≥2 databases that included DQ assessment information and excluded pharmacoeconomic studies or those with primary data collection. Three screening was performed using ASReview, a machine-learning platform. We mapped existing DQ definitions and extracted data on (i) multi-database working strategies, (ii) common data model (CDM) conversion, (iii) DQ dimensions and subdimensions and (iv) authors' reflections on DQ impact.

Results: From 16 087 identified papers, data were extracted from 79 entries. Approximately 40% of studies focused on drug safety, with a median of 3 [1–26] databases and a median of 230 820.5 [188–945 520 607] subjects. Opioids, COVID-19 vaccines and cardiovascular and COVID-19-related diseases were frequently studied. CDM usage was reported in 48% of studies (predominantly OMOP or ConcePTION). However, >80% of articles included information on extensiveness, reliability and validity DQ dimensions. Conversely, <50% reported on data security, governance, adaptability, usability or timeliness. These dimensions are related to data freshness, relevance to the research question and data comprehensiveness (e.g. source type, record creation and information contained). Less than 70% of studies assessed the impact of DQ on their results. The use of synonymous and homonymous terms by authors can complicate DQ assessment interpretation.

Conclusions: As networking and data sharing expand, especially post-COVID-19 pandemic, more clinical research utilizes multiple databases within distributed networks. Therefore, guidance on DQ is crucial for MDPES on medicines to ensure reliable results for clinicians.

#103

DNA differential methylation as a potential drug-induced liver injury biomarker and genome-wide DNA methylation functional analysis

J. A. Sanabria Cabrera^1,2,3, R. De Los Santos Fernández⁴, M. Villanueva Paz⁴, I. Alvarez Alvarez^4,5, H. Niu^4,5, C. Stephens⁵, J. Pinazo Bandera^4,5, R. J. Andrade Bellido^4,5, I. Medina Cáliz³ and M. I. Lucena González^1,5,3

¹Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Málaga, Spain; ²Plataforma ISCIII de Investigación Clínica, Madrid, Spain; ³Universidad de Málaga, Málaga, Spain; ⁴Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain; ⁵Centro de Investigación Biomédica en Red Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

Objective: This study aimed to identify affected cellular processes during DILI based on DNA methylation at CpG sites.

Material and/or methods: Peripheral blood DNA was extracted from 32 DILI patients enrolled in the Spanish DILI Registry and 32 healthy controls. DNA methylation analysis was performed using the Infinium MethylationEPIC BeadChip kit (Illumina). Whole-genome amplification and hybridization were performed using the BeadChip microarray (Illumina). Cytosine methylation state was assessed by single-base extension and analysed using the HiScan SQ module (Illumina). Analysis of differentially methylated CpG sites, gene ontology (GO), KEGG enrichment and kNN classification were done using R.

Results: A kNN classification analysis of the 347 most significantly differentially methylated CpG sites (FDR ≤ 0.05|Δ beta-value| ≥ 0.125) between the groups demonstrated an AUC = 0.965. Using a minimum p-value approach for the top 6 most significantly differentially methylated CpG sites resulted in an AUC = 0.932. A GO cellular component enrichment analysis revealed that the top cellular functions associated with the most significantly differentially methylated genes in DILI were related to cell junction processes and early endocytosis. A GO biological process enrichment analysis revealed that the most differentially methylated genes in DILI were related to adaptative immune system activation, especially T-cell activation. Regarding the KEGG pathway enrichment analysis, the most relevant pathways associated with differential methylation were those implicated in endocytosis, platelet activation, MAPK and T-cell receptor signalling.

Conclusions: This preliminary study demonstrates that differential CpG site methylation patterns can distinguish DILI from healthy controls. Moreover, the detected differences in CpG site methylation were associated with genes involved in diverse cell membrane processes (early endocytosis, cell–cell junction and signalling pathways) and adaptive immune system activation.

Funding: PI21/01248, JR21/00066, PT23/0013, JA.B1-05

#112

Features of idiosyncratic drug-induced liver injury (DILI) in Latin America: Long-term experience of the Latindili network

J. Sanabria Cabrera^1,2,3, F. Bessone⁴, N. Hernandez⁵, M. Arrese⁶, R. Parana⁷, C. Stephens⁸, I. Medina Cáliz³, I. Alvarez Alvarez^9,8, R. J. Andrade Bellido^9,3,8 and M. I. Lucena González^1,2,3,8

¹Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Málaga, Spain; ²Plataforma ISCIII de Investigación Clínica, Madrid, Spain; ³Universidad de Málaga, Málaga, Spain; ⁴Hospital Provincial del Centenario, Universidad de Rosario, Rosario, Argentina; ⁵Clínica de Gastroenterología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay; ⁶Departamento de Gastroenterología, Facultad de Medicina Pontificia Universidad Católica de Chile, Santiago, Chile; ⁷Hospital Universitário Prof. Edgard Santos-UFBA, Salvador, Brazil; ⁸Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain; ⁹Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain

Objective: To analyse features and outcomes of DILI in Latin America.

Material and/or methods: Information of DILI cases included in the LATINDILI database between 2011 and July 2022 was collected and analysed.

Results: Of 468 patients included, 13 had positive rechallenge and five recurrent DILI (different drugs). Mean age was 49 years (range 14–89), of which 62% were women. The most common type of injury was hepatocellular (62%). Overall, 42% of patients were hospitalized. Most cases were mild/moderate, but 6.2% were considered severe, and 4.1% resulted in death/liver transplantation. Overall, 11 cases (2.4%) developed chronic DILI (no biochemical resolution within 1 year), and nine had drug-induced autoimmune-like hepatitis (1.9%). Histological information was available for 80 patients (17%), of whom five had chronic cholestasis with ductopenia. The most frequent drugs were amoxicillin-clavulanate (12%), herbal and dietary supplements (HDS, 9%), anabolic androgenic steroids (4.9%), anti-tuberculosis medications (anti-TB) and nitrofurantoin (4.3% each). Among the 15 most common causative agents, all, but azathioprine, were associated with cases fulfilling nR-based Hy's law. However, only anti-TB, nimesulide and HDS were associated with worst outcome cases, while many were not, such as amoxicillin-clavulanate, nitrofurantoin and diclofenac. Causative agents more common in women included methyldopa (100%) nitrofurantoin (95%) and nimesulide (86%), while cyproterone (100%) and phenytoin (67%) were more common in men.

Conclusions: The increasing number of liver injuries associated with HDS is a major concern in Latin America. The predictive value of the nR-based Hy's law is drugspecific. These findings have regulatory implications for the promotion of public health, as common DILI-causing drugs in Latin America are either second-line drugs, are no longer in use or have been withdrawn from other markets due to liver toxicity.

Funding: AEMPS, CIBERehd, ISCIII-FEDER (PI21/01248, PI-0310-2018, JR21/00066, PT23/0013)

#52

Implementation of recommendation reports in pharmacogenetic studies: experience of collaboration between clinical biochemistry and pharmacology

M. E. Segura Molina¹, J. Navarro Roldán¹, E. M. Pérez López¹, J. L. Rubio Prieto², J. L. Garcia De Veas Silva², L. M. Rojas Herrera¹, P. Máiquez Asuero¹ and H. C. Macher Manzano²

¹Unidad de Gestión Clínica de Farmacología Clínica, Hospital Universitario Virgen del Rocío, Sevilla, Spain; ²Unidad de Gestión Clínica Laboratorios (Bioquímica Clínica), Hospital Universitario Virgen del Rocío, Sevilla, Spain

Objective: The implementation of pharmacogenetic studies in clinical practice allows for the optimization of patient treatment, reducing the incidence of adverse effects and improving therapeutic efficacy. This paper describes the experience of collaboration between clinical biochemistry and pharmacology in the implementation of pharmacogenetic studies. A report is developed that includes the interpretation of genetic results and personalized clinical recommendations.

Material and/or methods: Requests are received in clinical biochemistry. Sample analysis is performed by real-time PCR with Taqman probes on chips (OpenArray® technology on the QuantStudio™ 12K Flex Real-Time PCR System) (Thermo Fisher Scientific, Waltham, MA, USA). The preparation of the integrated report with clinical pharmacology recommendations was incorporated in late 2022.

Results: Since 2021, the study of the DPYD gene prior to treatment with fluoropyrimidines has been initiated (April 2021–December 2022). A total of 952 samples were analysed, 6% of which presented mutations. Between January 2023 and May 2024, 834 samples were received for the study of the DPYD gene (6% mutated). Treatment adjustment/modification recommendations were incorporated by clinical pharmacology. In addition, 23 studies have been carried out on patients for the analysis of other genes (CYP2C19, CYP2C9, CYP2D6 TPMT-NUDT15, SLCO1B1). Mental health (46%) and digestive (17%) are the main requesters. Seventy-eight genes were analysed (28% mutated genes). CYP2C19 has the highest number of variations with level 1A clinical recommendations according to guidelines (CPIC, DPWG, SEFF).

Conclusions: The preparation of reports with multidisciplinary participation improves the interpretation of genetic results and provides more precise clinical recommendations, including the assessment of other factors such as interactions. The incorporation of contraindication/prescription modification alerts in the medical record contributes to improving patient safety.

#42

Changes in quality of life in patients with type 2 diabetes treated with GLP-1 analogues

C. Roca Martínez¹, P. M. López Vázquez², A. Salgado Barreira¹, J. R. González Juanatey³ and J. Seijas Amigo³

¹Universidade de Santiago de Compostela, Santiago, Spain; ²Servicio Galego de Saúde, Dirección Xeral Asistencia Sanitaria, Santiago, Spain; ³Servicio de Cardiología, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain

Objective: To evaluate the impact of GLP-1 analogues on the overall well-being of patients, focusing on changes in quality of life.

Material and/or methods: An observational study was carried out in 13 healthcare centres. Subjects with type 2 diabetes and obesity who started treatment with aGLP-1 were included. A 44-week follow-up was carried out, including the measurement of anthropometric parameters (body mass index, abdominal diameter and weight change), laboratory parameters (Glucose, HbA1c, creatinine, c-LDL, non-HDL, c-HDL and triglycerides) and two quality of life questionnaires (EQ-5D-5L and SF-12) at the beginning and at the end of the study. The study was approved by Galician Ethics Committee.

Results: A total of 135 subjects were included (54% males, mean age 61.5 years). 28.9% of patients received subcutaneous semaglutide, 31.1% oral semaglutide, 34.8% dulaglutide, and 5.2% others (liraglutide and exenatide). Significant improvements were observed in several laboratory measures, in body mass index, in abdominal diameter and in weight. Initial and week 44 scores demonstrated improvements in EQ-5D indices (0.7 ± 0.2 vs. 0.8 ± 0.2; p < 0.001), in EQ-VAS (58.3 ± 22.4 vs. 65.3 ± 21.3; p < 0.01) and in SF-12 physical component scores (PCS) (39.8 ± 11.6 vs. 44.5 ± 12; p < 0.001), but not in SF-12 mental component (MCS) (49.4 ± 12.9 vs. 52.3 ± 11.5; p = 0.146). A subgroup analysis shows only patients on oral semaglutide treatment experienced a significant improvement in EQ-VAS (p = 0.045) and EQ-5D (p = 0.005) after 44 weeks of treatment.

Conclusions: GLP-1 analogues significantly improve the quality of life and clinical outcomes in patients with type 2 diabetes and obesity in real life.

#43

Ten-year evolution and health impact of precision oncology treatments in Catalonia

N. Puñet Valls^1,2, M. Umbria Vivancos¹, G. Puig Comas^1,2, J. M. Fontanet Sacristán^1,2, M. Gasol Boncompte^1,2 and A. Vallano Ferraz^1,3,2

¹Servei Català de la Salut, Barcelona, Spain; ²Universitat Autònoma de Barcelona, Barcelona, Spain; ³Institut Català de Salut, Barcelona, Spain

Objective: Personalized oncology, driven by the identification of specific tumour molecular alterations, has led to the commercialization of precision oncology medicines. This study examines the evolution of prescription patterns and associated expenditures related to precision oncological treatments.

Material and/or methods: We conducted an observational, retrospective cohort study analysing precision oncological treatments for solid neoplasms within the Catalan Health Service from 2013 to 2023. Data from the Patient and Treatment Registry (RPT) of the Catalan Health Service were used to collect information on treated patients, neoplasms, actionable molecular targets, medicines, overall patient survival and treatment costs.

Results: Over 10 years, 11 498 patients received precision oncological medications. The annual number of treated patients increased from 719 in 2013 to 2873 in 2023. The mean age at treatment initiation was 63.62 years (±12.83 years), of which 57.66% were men. The most common neoplasms were colorectal cancer (40%), non-small cell lung cancer (33%) and melanoma (12%). Identified molecular targets included RAS (43%), EGFR (28%), BRAF (17%) and ALK (6%). Key medicines used were cetuximab (2791 patients, 24.27%), panitumumab (1935 patients, 18.41%) and erlotinib (1312 patients, 11.41%). Mean overall survival was 20.7 months (±23.78), varying from 26.6 months (±20.7) for BRCA1-targeted treatments to 15.5 months (±17) for BRAF-targeted treatments. Total treatment cost increased from €16.4 million in 2013 to €51.4 million in 2023. Average cost per patient rose from €9722 in 2013 to €18 145 in 2023. In 2023, expenditures on medicines targeting EGFR reached €17.6 million, while treatments directed at BRAC1 and ALK accounted for €6.7 million each.

Conclusions: The progressive increase in patients treated with precision oncology medicines and associated costs underscores the growing health and economic impact. Variability in patient survival and expenditure among different medicines groups highlights the need for monitoring and optimizing healthcare resources and decision-making.

#58

A model for the clinical management of the introduction of new medicines in Vall D'Hebron University Hospital (VHUH)

I. Danés Carreras^1,2,3, A. Agustí Escasany^1,2,3, E. Ballarín Alins^1,3, M. Q. Gorgas Torner⁴, P. Marrero Álvarez⁴, M. Vila Martínez⁵, S. Cortés García⁵, M. J. Abadias Medrano⁶ and E. Diogène Fadini^1,2,3

¹Clinical Pharmacology Service, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; ²Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Barcelona, Spain; ³Clinical Pharmacology Research Group, Vall d'Hebron Research Institute, Barcelona, Spain; ⁴Pharmacy Service, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; ⁵Financial Resources Direction, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; ⁶Medical Direction, Vall d'Hebron University Hospital, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain

Objective: To describe our model for the clinical management of new medicines based on the activity developed by the Hospital Outpatient Treatments (HOT) Committee.

Material and/or methods: A descriptive analysis of regular meetings held between 2016 and 2023 with 12 selected clinical services/units that generated the most expenditure in HOT at VHUH was performed. The fixed agenda of the meetings includes information on drugs in advanced stages of authorization and on newly approved drugs (including financing conditions set by the public health system), review of recommendations and follow-up of compliance with data collection in the Register of Treated Patients, drug expenditure, number of treated patients, indicators and agreements.

Results: During the study period, 242 meetings were held. Most agreements were related to the need to improve registry data (37.7%), promoting the use of generic/biosimilar drugs (18.3%) and proposing clinical initiatives to improve efficiency (8.5%). HOT expenditure in the selected services increased from €109 417 804 in 2016 to €153 447 229 in 2023 (40.2%; 54.3% for the whole HUVH). The number of treated patients increased a 55.4%, and the cost per patient decreased a 9.7%. The greatest HOT expenditure was observed in haematology and oncology; the most marked increases occurred in pneumology and allergology. The number of treated patients increased in all the services, except in hepatology. An effort was made to use the most efficient drugs in infectious diseases and rheumatology services. Follow-up of patients to assess the appropriateness/effectiveness of some HOT was organized in allergology and gastroenterology services.

Conclusions: A multidisciplinary model for the clinical management and follow-up of new medications has been consolidated. In the services/units in which meetings were held, a lower increase in HOT expenditure was observed. Having a method for the introduction and monitoring of new medications helps to set up an organized and reasoned decision-making process.

#63

Availability of new drugs for children: Impact assessment of the European regulation on medicinal products for paediatric use

E. Blanco Reina¹, C. Pérez Muñoz², E. Pérez Barreales², C. Stephens³ and I. Bellido Estévez¹

¹Dpto. Farmacología y Pediatría, Facultad de Medicina, Universidad de Málaga, IBIMA – Plataforma BIONAND, Málaga, Spain; ²Dpto. Farmacología y Pediatría, Facultad de Medicina, Universidad de Málaga, Málaga, Spain; ³IBIMA Plataforma BIONAND, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, CIBERehd, Málaga, Spain

Objective: To assess the impact of the European Regulation on Paediatric Medicinal Products since its implementation in 2007 to the present day, regarding number of new authorized drugs and variations in the Summaries of Product Characteristics (SmPC), all of which refer to the use of medicines in children. Also, to determine the proportion of orphan drugs approved for paediatric use, their profile, financing status and availability.

Material and/or methods: Longitudinal study with retrospective data collection. All the marketing authorizations granted by the Committee for Medicinal Products for Human Use (CHMP) were analysed by reviewing the AEMPS Monthly Bulletins for the period of 2007–2023. Other sources of information were the SmPC and the EMA Orphan designation. To determine the funding status, Nomenclator was consulted.

Results: During the study period, a total of 843 new medications were authorized, of which 26.1% (220) have a paediatric indication. The groups with the highest number of approved uses for children were antineoplastic and immunomodulatory agents (20.9%), followed by anti-infectives (20.4%) and drugs for the alimentary tract and metabolism (16.8%), with enzyme replacement therapies standing out in the last group. 46.36% of the drugs were designated as orphan drugs, but up to 40% of the cases were not funded.

SmPC variations that refer to the paediatric population accounted for 38.83% of the total number of changes (320 out of 824). The most frequent category of variation was extension of use from the adult population to children (41.9%), followed by extension from other paediatric ages (26.9%). In this case, 34.4% belonged to group J (anti-infectives).

Conclusions: The Paediatric Medicines Regulation has had a very positive impact on the availability of medicines for children. Just over a quarter of new marketing authorizations are for medicines that include paediatric use. Of these, almost half are orphan medicines. Advanced therapies, especially gene therapy, also show remarkable development.

#75

Effectiveness and cost of monoclonal antibodies against CGRP for migraine in the Catalan public healthcare system

G. Tarraso Urios¹, M. Umbria Vivancos¹, N. Paco Zamora¹, R. Vives Vilagut¹, M. Gasol Boncompte^1,2 and A. Vallano Ferraz^1,3,2

¹Servei Català de la Salut, Barcelona, Spain; ²Universitat Autònoma de Barcelona, Barcelona, Spain; ³Intitut Català de la Salut, Barcelona, Spain

Objective: Few studies have evaluated the effectiveness of monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) for migraine in real-world clinical practice. This study aimed to analyse the effectiveness and budget impact of these medicines within the public healthcare system of Catalonia.

Material and/or methods: A retrospective study was conducted using data from the Patient and Treatment Registry of the Catalan Health Service (2019–2023). Patients treated with mAbs were selected. Demographic and clinical data were collected for patients who received these medicines, including treatment response, use of rescue medication, total costs and cost per treated patient.

Results: Over the 5-year period, there has been a progressive increase in the number of treated patients and associated costs. A total of 5605 patients were treated, of whom 85.3% were women, with a mean (SD) age of 47.7 years (11.8). These patients had a mean (SD) of 17 (8) migraine episodes per month in the 3 months prior to starting treatment and a mean (SD) HIT-6 score of 66 (15). Between 3 and 6 months after starting treatment, 44.9% of patients experienced a reduction of more than 50% in the monthly frequency of migraine episodes, and 58.5% a decrease of at least 30%. Additionally, there was a 33% reduction in the use of rescue medication. Total expenditure increased from €19 800 in 2019 to €8 340 683 in 2023, with a cost per patient of €1775.

Conclusions: The results of this study demonstrate that mAbs against CGRP are effective in real-world clinical practice for reducing the frequency of migraine episodes and the use of rescue medication. However, these clinical benefits are associated with a significant increase in healthcare costs, presenting a challenge for the sustainability of the public healthcare system. Balancing clinical effectiveness with economic impact is essential to ensure the long-term viability of these treatments in public healthcare.

#81

Evaluation of non-response to antiplatelet therapy with acetylsalicylic acid in patients with event or high cardiovascular risk

L. Ortega Hombrados¹, E. Martín Aurioles², M. D. Rodríguez Pérez¹, A. M. Sánchez Tévar¹, C. Verdugo Cabello¹, M. M. Arrebola Ramírez³, J. P. De La Cruz Cortés¹ and J. A. González Correa¹

¹Departamento de Farmacología (Grupo de Investigación A07-IBIMA, CTS655-PAIDI), Facultad De Medicina, Universidad De Málaga. IBIMA-Plataforma BIONAND, Málaga, Spain; ²UGC “La Roca”, Distrito Sanitario Málaga-Guadalhorce, Málaga, Spain; ³UGC de Análisis Clínico, Hospital Básico de la Axarquía, Málaga, Spain

Objective: The main objective was to assess the prevalence of non-response to antiplatelet therapy with acetylsalicylic acid in patients with event or high cardiovascular risk. As a secondary objective was to assess biochemical factors associated with non-response to antiplatelet therapy with acetylsalicylic acid and to assess whether type 2 diabetes mellitus acts as an independent factor in the lack of response to antiplatelet therapy.

Material and/or methods: As the main outcome variable, response to antiplatelet therapy was assessed using PFA-100 methodology. We also assessed the possibility of reversing the lack of response to antiplatelet therapy. For this purpose, an in vitro study was performed in which a sample of the subject's blood is incubated with increasing concentrations of acetylsalicylic acid (ASA). This test is performed following the methodology of antiaggregation assessment by electrical impedance aggregometry. In addition, some oxidative stress and vascular inflammation variables such as lipoperoxides, peroxynitrites or prostanoids were analysed by enzyme immunoassay kits.

Results: The prevalence of non-response in the population analysed (n = 320) was 60%. The prevalence of non-response in diabetics was 72.4% versus 54.5% in non-diabetic patients. In blood samples from patients with diabetes, the reversibility of non-response was significantly lower (3.5% of samples from diabetic patients vs. 18% of samples from non-diabetic patients). We observed that in patients with a lack of response, biochemical parameters reflecting vascular inflammation were significantly increased, as well as some oxidative stress parameters.

Conclusions: More than half of patients at high cardiovascular risk have a lack of response to antiplatelet therapy. Diabetes mellitus acts as an independent factor on non-response to ASA treatment. In addition, increased oxidative stress and vascular inflammation are associated with a lack of response to antiplatelet therapy.

#90

Independent scientific production based on BIFAP, the AEMPS database of real-world-data from the Spanish primary healthcare system

M. Maciá Martínez, R. Martínez Muñoz, M. Gil García and B. Ceinos Garrido

Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain

Objective: BIFAP is an anonymized population-based database from primary care records of the National Health System (SNS). The AEMPS has put BIFAP at the service of independent researchers, as a tool that allows quality pharmacoepidemiological studies. The objective is to describe the scientific production that BIFAP generates through the projects reviewed by its Scientific Committee.

Material and/or methods: The BIFAP project management tool TRAZA has been used. The projects reviewed by the BIFAP Scientific Committee were extracted. Those that have generated at least one publication have been analysed, including projects of the AEMPS or independent researchers.

Results: Of the 146 projects evaluated by the BIFAP Scientific Committee, 24 received an unfavourable opinion, and 122 (84%) a favourable opinion. Of those, 109 (89%) have been completed. Of the 109 completed studies, 72 finalized (66%), and 37 remain active (34%) and 41 (56% of completed projects) have generated at least one scientific publication. Of them, 67.5% correspond to projects carried out by independent researchers and 32.5% to projects led by the AEMPS.

Conclusions: The maintenance by the AEMPS of BIFAP, which currently contains the primary care EHR of more than 22 million patients, with an average follow-up of 10 years, has been possible thanks to the collaboration with the healthcare services of 11 autonomous communities and to the work of primary care doctors, the backbone and gatekeepers of the SNS. BIFAP is a secondary data source useful for the generation of scientific knowledge at the service of independent researchers and the AEMPS. This is demonstrated by a relevant number of publications. The majority from researchers outside the AEMPS.

#101

Dissecting ChatGPT 4o: Is it really able to justify therapeutic recommendations for attention deficit hyperactivity disorder?

D. Ramírez Saco^1,2, E. Baykova^3,4, C. Lombardía⁵, D. Serrano^4,6, R. Cunill⁷, Ò. Raya⁸, B. López⁸ and X. Castells²

¹Department of Clinical Pharmacology, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain; ²TransLab Research Group, Department of Medical Sciences, University of Girona, Girona, Spain; ³Child and Juvenile Mental Health Centre Selva Marítima, Institut d'Assistència Sanitària, Blanes, Girona, Spain; ⁴Mental Health and Addictions Research Group, Institut d'Investigació Biomèdica de Girona, Salt, Girona, Spain; ⁵Child and Juvenile Mental Health Centre Gironès – Pla de l'Estany, Institut d'Assistència Sanitària, Girona, Spain; ⁶Acute Psychiatry Hospitalization Service, Parc Hospitalari Martí i Julià, Institut d'Assistència Sanitària, Salt, Girona, Spain; ⁷Acute Patients Unit, Parc sanitari Sant Joan de Déu Numància, Barcelona, Spain; ⁸Control Engineering and Intelligent Systems (eXiT), Department of Electrical, Electronic and Automatic Engineering, University of Girona, Girona, Spain

Objective: To compare therapeutic recommendations for attention deficit hyperactivity disorder (ADHD) patients between ChatGPT-4o, TDApp and the Spanish ADHD guideline. To assess the ability of ChatGPT-4o to provide suitable references supporting ADHD treatment selection.

Material and/or methods: We conducted an observational study involving 32 paediatric ADHD patients, comparing pharmacological treatment recommended from three sources: ChatGPT-4o, TDApp (an artificial intelligence-driven medical decision support system providing personalized ADHD treatment recommendations based on the latest scientific evidence with the patients and clinicians' preferences) and the national guideline. For each patient, ChatGPT-4o was requested to provide a clinical trial reference supporting its recommendations. These references were assessed for suitability based on alignment with patient demographic features and trial inclusion/exclusion criteria.

Results: Regarding demographic characteristics, 65.6% of patients were male, with 53.1% being children (mean age 12.3 years), and 37.5% had current comorbidities. ChatGPT-4o (mean of 4.19 recommendations per patient, ranging from 2.0 to 5.0) and the Spanish clinical practice guideline (mean 3.72, ranging from 2.0 to 4.0) provided a similar number of therapeutic options, most frequently recommending atomoxetine. In contrast, TDApp provided fewer recommendations (mean of 1.91, ranging from 0.0 to 5.0), likely due to scarce evidence in patient subgroups, and suggested methylphenidate derivates as the most frequent treatment. Excluding minor errors (e.g. misreferenced PubMed ID or DOI), ChatGPT-4o was able to provide a recognizable clinical trial references for 81.3% of patients, but only 28.2% received a valid reference meeting inclusion/exclusion criteria.

Conclusions: ChatGPT-4o offered similar treatment recommendations, in terms of number and drug predominance as the Spanish guideline, differing from TDApp. Nevertheless, ChatGPT-4o's ability to provide suitable references for personalized ADHD treatment is limited.

#16

Antiplatelet drugs as chemopreventive agents for digestive cancer (AD-DC): A cohort study

E. Fernández Antón¹, A. Rodríguez Miguel¹, M. Gil², A. Castellano López³, L. A. García Rodríguez⁴ and F. J. De Abajo^1,5

¹Pharmacology Unit, Department of Biomedical Sciences, University of Alcalá (IRYCIS), Alcalá De Henares, Spain; ²BIFAP Unit, Pharmacoepidemiology and Pharmacovigilance Division, Spanish Agency of Medicines and Medical Devices (AEMPS), Madrid, Spain; ³Gastroenterology Service, University Hospital Príncipe de Asturias, Alcalá De Henares, Spain; ⁴Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain; ⁵Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Alcalá de Henares, Spain

Objective: Digestive cancer including oesophageal, gastric, pancreatic, hepatobiliary and colorectal (CRC) rank among the most common and deadly. Increased COX-2 expression seems to be involved in their tumorigenesis, which could explain the chemopreventive action of COX-2 inhibitors, especially on colorectal adenomas and cancer. Low-dose acetylsalicylic acid (ldASA) has also been acknowledged as a chemopreventive agent, but at such doses, a direct systemic effect on COX-2 seems implausible, so an indirect effect through platelet deactivation have been hypothesized. If so, then other antiplatelet drugs (ADs) might share this effect. The aim of the present study was to assess the chemopreventive effect of different types of ADs on colorectal and other digestive cancers.

Material and/or methods: A cohort study comparing new users of ADs with non-users was conducted from 2001 to 2019 using the electronic healthcare database BIFAP. Non-users were matched with users 1:1 by age and sex. Adjusted hazard ratios (HR) and 95% CIs were obtained for Ads grouped by COX-1 inhibitors (iCOX-1) and P2Y12 inhibitors (iP2Y12), adjusted for competing risks.

Results: A total of 1 155 106 individuals were included, of whom 577 553 new users of ADs (503 996 ldASA). We identified 32 880 incident digestive cancer cases (21 258 CRC). A risk reduction was observed with iCOX-1 for all types of cancer (overall HR 0.63; 95% CI: 0.61–0.65). A significant reduction was also observed with iP2Y12 for colorectal, gastric and pancreatic cancer (overall HR 0.70; 95% CI: 0.65–0.75).

Conclusions: This study supports the hypothesis that ADs, regardless of their mechanism of action, have a chemopreventive effect on colorectal, gastric and pancreatic cancer. The next step will be to estimate the incidence of major bleedings caused by ADs within the same cohort in order to appraise the benefit–risk ratio.

Study funded by the AES-ISCIII (PI20/01807) and co-financed by FEDER.