Modelo farmacogenético y clínico para la predicción de desenlaces en pacientes con artritis reumatoide tratados con metotrexato y adalimumab

GOAL: To develop a pharmacogenetic and clinical model to predict effectiveness outcomes in a cohort of patients diagnosed with rheumatoid arthritis (RA) treated with methotrexate or adalimumab at the Central Military Hospital in Bogota, Colombia. METHODS: Five statistical learning methods were teste...

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Detalles Bibliográficos
Autor: Hernández Tarapués, Fabián Alberto
Tipo de recurso: tesis de maestría
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:Colombia
Institución:Universidad Nacional de Colombia
Repositorio:Repositorio UN
Idioma:español
OAI Identifier:oai:repositorio.unal.edu.co:unal/78759
Acceso en línea:https://repositorio.unal.edu.co/handle/unal/78759
Access Level:acceso abierto
Palabra clave:610 - Medicina y salud::615 - Farmacología y terapéutica
Artritis Reumatoide
Farmacogenética
Modelo predictivo
Aprendizaje Automático
Rheumatoid Arthritis
Pharmacogenetics
Predictive Model
Machine Learning
Descripción
Sumario:GOAL: To develop a pharmacogenetic and clinical model to predict effectiveness outcomes in a cohort of patients diagnosed with rheumatoid arthritis (RA) treated with methotrexate or adalimumab at the Central Military Hospital in Bogota, Colombia. METHODS: Five statistical learning methods were tested on the data set with previous pre-processing for variable cleaning and selection: Logistic regression, decision trees, random forests, Support Vector Machines (SVM) and Artificial Neural Networks (ANN). The models were applied in a cohort of 155 patients treated with MTX which was derived in a training (124 patients) and a test cohort (31 patients). Both clinical variables and genetic variations were included. The chosen outcome was the therapy response measured as a DAS 28 score <3.2. The performance evaluation criterion was the area (AUC) under the receiver operating characteristics (ROC) curve. RESULTS: The algorithms with the highest predictive power were SVM and ANN. For the MTX cohort, the main selected variables were age, time with RA, functional classification, and genotypes of the rs9344, rs4148396, rs4673993, rs1801133 and rs7279445 variants. Given the size of the cohort of ADA-treated patients (12 patients), no machine learning model could be successfully adjusted. CONCLUSIONS: A prognostic model with high predictive power was developed in the cohort of patients treated with MTX, which is able to identify patients prone to not responding well to treatment.