Journal of Clinical Medicine (Aug 2022)
Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab
- 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
Affiliations
- María Chaparro
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain
- Iria Baston-Rey
- Complejo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, Spain
- Estela Fernández Salgado
- Complejo Hospitalario de Pontevedra, 36164 Pontevedra, Spain
- Javier González García
- Hospital Público Comarcal la Inmaculada, 04600 Almería, Spain
- Laura Ramos
- Hospital Universitario de Canarias, 38320 Tenerife, Spain
- María Teresa Diz-Lois Palomares
- Hospital Universitario A Coruña, 15006 A Coruña, Spain
- Federico Argüelles-Arias
- Hospital Universitario Virgen Macarena, 41009 Seville, Spain
- Eva Iglesias Flores
- Hospital Universitario Reina Sofía, 14004 Córdoba, Spain
- Mercedes Cabello
- Hospital Universitario Virgen de Valme, 41014 Seville, Spain
- Saioa Rubio Iturria
- Complejo Hospitalario de Navarra, 31008 Pamplona, Spain
- Andrea Núñez Ortiz
- Hospital Universitario Virgen del Rocío, 41013 Seville, Spain
- Mara Charro
- Hospital de Barbastro, 22300 Barbastro, Spain
- Daniel Ginard
- Hospital Universitario Son Espases, 07120 Palma, Spain
- Carmen Dueñas Sadornil
- Hospital San Pedro de Alcántara, 10003 Cáceres, Spain
- Olga Merino Ochoa
- Hospital Universitario Cruces, 48903 Barakaldo, Spain
- David Busquets
- Hospital Universitari de Girona Doctor Josep Trueta, 17007 Girona, Spain
- Eduardo Iyo
- Hospital Comarcal de Inca, 07300 Inca, Spain
- Ana Gutiérrez Casbas
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
- Patricia Ramírez de la Piscina
- Hospital Universitario de Araba-Txagorritxu, 01004 Vitoria-Gasteiz, Spain
- Marta Maia Boscá-Watts
- Hospital Clínico Universitario de Valencia, 46010 Valencia, Spain
- Maite Arroyo
- Hospital Clínico Universitario Lozano Blesa, 50009 Zaragoza, Spain
- María José García
- Hospital Universitario Marqués de Valdecilla, IDIVAL, 39008 Santander, Spain
- Esther Hinojosa
- Hospital de Manises, 46940 Manises, Spain
- Jordi Gordillo
- Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain
- Pilar Martínez Montiel
- Hospital Universitario 12 de Octubre, 28041 Madrid, Spain
- Benito Velayos Jiménez
- Hospital Clínico Universitario de Valladolid, 47003 Valladolid, Spain
- Cristina Quílez Ivorra
- Hospital Marina Baixa, 03570 Villajoyosa, Spain
- Juan María Vázquez Morón
- Hospital Universitario Juan Ramón Jiménez, 21002 Huelva, Spain
- José María Huguet
- Hospital General Universitario de Valencia, 46014 Valencia, Spain
- Yago González-Lama
- Hospital Universitario Puerta de Hierro, 28222 Majadahonda, Spain
- Ana Isabel Muñagorri Santos
- Hospital Universitario de Donostia, 20014 Donostia-San Sebastián, Spain
- Víctor Manuel Amo
- Hospital Regional de Málaga, 29010 Málaga, Spain
- María Dolores Martín Arranz
- Hospital Universitario de La Paz, 28046 Madrid, Spain
- Fernando Bermejo
- Instituto de Investigación Sanitaria del Hospital La Paz (IdiPaz), 28046 Madrid, Spain
- Jesús Martínez Cadilla
- Hospital Alvaro Cunqueiro, 36213 Vigo, Spain
- Cristina Rubín de Célix
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain
- Paola Fradejas Salazar
- Hospital Virgen de la Concha, 49022 Zamora, Spain
- Antonio López San Román
- Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain
- Nuria Jiménez
- Hospital General Universitario de Elche, 03203 Elche, Spain
- Santiago García-López
- Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain
- Anna Figuerola
- Hospital General Universitario de Castellón, 12004 Castellón de la Plana, Spain
- Itxaso Jiménez
- Hospital Universitario de Galdakao-Usansolo, 48960 Galdakao, Spain
- Francisco José Martínez Cerezo
- Hospital Universitario Sant Joan de Reus, 43204 Reus, Spain
- Carlos Taxonera
- Hospital Clínico Universitario San Carlos, Instituto de Investigación del Hospital Clínico San Carlos [IdISSC], 28040 Madrid, Spain
- Pilar Varela
- Hospital Universitario de Cabueñes, 33203 Gijón, Spain
- Ruth de Francisco
- Hospital Universitario Central de Asturias, Instituto de Investigación Biosanitaria del Principado de Asturias [ISPA], 33011 Oviedo, Spain
- David Monfort
- Consorci Sanitari de Terrassa, 08227 Terrassa, Spain
- Gema Molina Arriero
- Complejo Hospitalario Universitario de Ferrol, 15405 Ferrol, Spain
- Alejandro Hernández-Camba
- Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
- Francisco Javier García Alonso
- Hospital Universitario Rio Hortega, 47012 Valladolid, Spain
- Manuel Van Domselaar
- Hospital Universitario de Torrejón, 28850 Torrejón de Ardoz, Spain
- Ramón Pajares-Villarroya
- Hospital Universitario Infanta Sofía, 28702 San Sebastián de los Reyes, Spain
- Alejandro Núñez
- Hospital Clínico Universitario de Salamanca, 37007 Salamanca, Spain
- Francisco Rodríguez Moranta
- Hospital Universitario Bellvitge, 08907 L’Hospitalet de Llobregat, Spain
- Ignacio Marín-Jiménez
- Hospital Universitario Gregorio Marañón, 28009 Madrid, Spain
- Virginia Robles Alonso
- Hospital Universitario Vall d’Hebrón, 08035 Barcelona, Spain
- María del Mar Martín Rodríguez
- Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain
- Patricia Camo-Monterde
- Hospital Universitario San Jorge, 22004 Huesca, Spain
- Iván García Tercero
- Hospital General Universitario Santa Lucía, 30202 Cartagena, Spain
- Mercedes Navarro-Llavat
- Hospital de Sant Joan Despí Moisès Broggi, 08970 Sant Joan Despí, Spain
- Lara Arias García
- Hospital Universitario de Burgos, 09006 Burgos, Spain
- Daniel Hervías Cruz
- Hospital General Universitario de Ciudad Real, 13005 Ciudad Real, Spain
- Sebastian Kloss
- Janssen, EMEA, 2340 Beerse, Belgium
- Alun Passey
- Janssen, EMEA, 2340 Beerse, Belgium
- Cynthia Novella
- Janssen Medical Department, Paseo Doce Estrellas, 5-7, 28042 Madrid, Spain
- Eugenia Vispo
- Janssen Medical Department, Paseo Doce Estrellas, 5-7, 28042 Madrid, Spain
- Manuel Barreiro-de Acosta
- Complejo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, Spain
- Javier P. Gisbert
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, 28006 Madrid, Spain
- DOI
- https://doi.org/10.3390/jcm11154518
- Journal volume & issue
-
Vol. 11,
no. 15
p. 4518
Abstract
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.
Keywords