1. Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab
- Author
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María Chaparro, Iria Baston-Rey, Estela Fernández Salgado, Javier González García, Laura Ramos, María Teresa Diz-Lois Palomares, Federico Argüelles-Arias, Eva Iglesias Flores, Mercedes Cabello, Saioa Rubio Iturria, Andrea Núñez Ortiz, Mara Charro, Daniel Ginard, Carmen Dueñas Sadornil, Olga Merino Ochoa, David Busquets, Eduardo Iyo, Ana Gutiérrez Casbas, Patricia Ramírez de la Piscina, Marta Maia Boscá-Watts, Maite Arroyo, María José García, Esther Hinojosa, Jordi Gordillo, Pilar Martínez Montiel, Benito Velayos Jiménez, Cristina Quílez Ivorra, Juan María Vázquez Morón, José María Huguet, Yago González-Lama, Ana Isabel Muñagorri Santos, Víctor Manuel Amo, María Dolores Martín Arranz, Fernando Bermejo, Jesús Martínez Cadilla, Cristina Rubín de Célix, Paola Fradejas Salazar, Antonio López San Román, Nuria Jiménez, Santiago García-López, Anna Figuerola, Itxaso Jiménez, Francisco José Martínez Cerezo, Carlos Taxonera, Pilar Varela, Ruth de Francisco, David Monfort, Gema Molina Arriero, Alejandro Hernández-Camba, Francisco Javier García Alonso, Manuel Van Domselaar, Ramón Pajares-Villarroya, Alejandro Núñez, Francisco Rodríguez Moranta, Ignacio Marín-Jiménez, Virginia Robles Alonso, María del Mar Martín Rodríguez, Patricia Camo-Monterde, Iván García Tercero, Mercedes Navarro-Llavat, Lara Arias García, Daniel Hervías Cruz, Sebastian Kloss, Alun Passey, Cynthia Novella, Eugenia Vispo, Manuel Barreiro-de Acosta, Javier P. Gisbert, Institut Català de la Salut, [Chaparro M] Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. [Baston-Rey I] Complejo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain. [Fernández Salgado E] Complejo Hospitalario de Pontevedra, Pontevedra, Spain. [González García J] Hospital Público Comarcal la Inmaculada, Almería, Spain. [Ramos L] Hospital Universitario de Canarias, Tenerife, Spain. [Diz-Lois Palomares MT] Hospital Universitario A Coruña, A Coruña, Spain. [Robles Alonso V] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinflamatorios [COMPUESTOS QUÍMICOS Y DROGAS] ,predictive factors ,Factors de risc en les malalties ,Risk factors in diseases ,Crohn’s Disease ,ustekinumab ,Antiinflamatoris - Ús terapèutic ,Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Inflammatory Bowel Diseases::Crohn Disease [DISEASES] ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Crohn's Disease ,General Medicine ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::enfermedad inflamatoria intestinal::enfermedad de Crohn [ENFERMEDADES] ,Crohn, Malaltia de - Tractament ,Ciencias de la información::metodologías computacionales::algoritmos::inteligencia artificial::aprendizaje automático [CIENCIA DE LA INFORMACIÓN] ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Inflammatory Agents [CHEMICALS AND DRUGS] ,Malaltia de Crohn ,Aprenentatge automàtic ,Information Science::Computing Methodologies::Algorithms::Artificial Intelligence::Machine Learning [INFORMATION SCIENCE] - Abstract
Malaltia de Crohn; Factors predictius; Ustekinumab Enfermedad de Crohn; Factores predictivos; Ustekinumab Crohn’s disease; Predictive factors; Ustekinumab Ustekinumab has shown efficacy in Crohn’s Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients’ data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index ≤ 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission. This work was supported by Janssen-Cilag Spain. This sponsor had a partial role in study design, analysis, and interpretation of data.
- Published
- 2022