Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn's Disease Patients on Ustekinumab
Por:
Chaparro, M, Baston-Rey, I, Salgado, EF, Garcia, JG, Ramos, L, Palomares, MTDL, Arguelles-Arias, F, Flores, EI, Cabello, M, Iturria, SR, Ortiz, AN, Charro, M, Ginard, D, Sadornil, CD, Ochoa, OM, Busquets, D, Iyo, E, Casbas, AG, de la Piscina, PR, Bosca-Watts, MM, Arroyo, M, Garcia, MJ, Hinojosa, E, Gordillo, J, Montiel, PM, Jimenez, BV, Ivorra, CQ, Moron, JMV, Huguet, JM, Gonzalez-Lama, Y, Santos, AIM, Amo, VM, Arranz, MDM, Bermejo, F, Cadilla, JM, de Celix, CR, Salazar, PF, San Roman, AL, Jimenez, N, Garcia-Lopez, S, Figuerola, A, Jimenez, I, Cerezo, FJM, Taxonera, C, Varela, P, de Francisco, R, Monfort, D, Arriero, GM, Hernandez-Camba, A, Alonso, FJG, Van Domselaar, M, Pajares-Villarroya, R, Nunez, A, Moranta, FR, Marin-Jimenez, I, Alonso, VR, Rodriguez, MDM, Camo-Monterde, P, Tercero, IG, Navarro-Llavat, M, Garcia, LA, Cruz, DH, Kloss, S, Passey, A, Novella, C, Vispo, E, Barreiro-de Acosta, M, Gisbert, JP
Publicada:
1 ago 2022
Resumen:
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.
Filiaciones:
Chaparro, M:
Univ Autonoma Madrid, Hosp Univ La Princesa, Inst Invest Sanitaria Princesa IIS IP, Madrid 28006, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 28029, Spain
Baston-Rey, I:
Complejo Hosp Univ Santiago, Santiago De Compostela 15706, Spain
Salgado, EF:
Complejo Hosp Pontevedra, Pontevedra 36164, Spain
Garcia, JG:
Hosp Publ Comarcal Inmaculada, Almeria 04600, Spain
Ramos, L:
Hosp Univ Canarias, Tenerife 38320, Spain
Palomares, MTDL:
Hosp Univ A Coruna, La Coruna 15006, Spain
Arguelles-Arias, F:
Hosp Univ Virgen Macarena, Seville 41009, Spain
Univ Seville, Fac Med, Seville 41009, Spain
Flores, EI:
Hosp Univ Reina Sofia, Cordoba 14004, Spain
Cabello, M:
Hosp Univ Virgen de Valme, Seville 41014, Spain
Iturria, SR:
Complejo Hosp Navarra, Pamplona 31008, Spain
Ortiz, AN:
Hosp Univ Virgen del Rocio, Seville 41013, Spain
Charro, M:
Hosp Barbastro, Barbastro 22300, Spain
Ginard, D:
Hosp Univ Son Espases, Palma De Mallorca 07120, Spain
Sadornil, CD:
Hosp San Pedro Alcantara, Caceres 10003, Spain
Ochoa, OM:
Hosp Univ Cruces, Baracaldo 48903, Spain
Busquets, D:
Hosp Univ Girona Doctor Josep Trueta, Girona 17007, Spain
Iyo, E:
Hosp Comarcal Inca, Inca 07300, Spain
Casbas, AG:
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 28029, Spain
Hosp Gen Univ Alicante, Inst Invest Sanitaria & Biomed Alicante ISABIAL, Alicante 03010, Spain
de la Piscina, PR:
Hosp Univ Araba Txagorritxu, Vitoria 01004, Spain
Bosca-Watts, MM:
Hosp Clin Univ Valencia, Valencia 46010, Spain
Arroyo, M:
Hosp Clin Univ Lozano Blesa, Zaragoza 50009, Spain
Garcia, MJ:
Hosp Univ Marques de Valdecilla, IDIVAL, Santander 39008, Spain
Hinojosa, E:
Hosp Manises, Manises 46940, Spain
Gordillo, J:
Hosp Santa Creu & Sant Pau, Barcelona 08041, Spain
Montiel, PM:
Hosp Univ 12 Octubre, Madrid 28041, Spain
Jimenez, BV:
Hosp Clin Univ Valladolid, Valladolid 47003, Spain
Ivorra, CQ:
Hosp Marina Baixa, Villajoyosa 03570, Spain
Moron, JMV:
Hosp Univ Juan Ramon Jimenez, Huelva 21002, Spain
Huguet, JM:
Hosp Gen Univ Valencia, Valencia 46014, Spain
Gonzalez-Lama, Y:
Hosp Univ Puerta de Hierro, Majadahonda 28222, Spain
Santos, AIM:
Hosp Univ Donostia, Donostia San Sebastian 20014, Spain
Amo, VM:
Hosp Reg Malaga, Malaga 29010, Spain
Arranz, MDM:
Hosp Univ La Paz, Madrid 28046, Spain
Inst Invest Sanitaria Hosp La Paz IdiPaz, Madrid 28046, Spain
Bermejo, F:
Inst Invest Sanitaria Hosp La Paz IdiPaz, Madrid 28046, Spain
Hosp Univ Fuenlabrada, Fuenlabrada 28942, Spain
Cadilla, JM:
Hosp Alvaro Cunqueiro, Vigo 36213, Spain
de Celix, CR:
Univ Autonoma Madrid, Hosp Univ La Princesa, Inst Invest Sanitaria Princesa IIS IP, Madrid 28006, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 28029, Spain
Salazar, PF:
Hosp Virgen de la Concha, Zamora 49022, Spain
San Roman, AL:
Hosp Univ Ramon y Cajal, Madrid 28034, Spain
Jimenez, N:
Hosp Gen Univ Elche, Elche 03203, Spain
Garcia-Lopez, S:
Hosp Univ Miguel Servet, Zaragoza 50009, Spain
Figuerola, A:
Hosp Gen Univ Castellon, Castellon De La Plana 12004, Spain
Jimenez, I:
Hosp Univ Galdakao Usansolo, Galdakao 48960, Spain
Hosp Univ Gregorio Maranon, Madrid 28009, Spain
Cerezo, FJM:
Hosp Univ St Joan Reus, Reus 43204, Spain
Taxonera, C:
Hosp Clin Univ San Carlos, Hosp Clin San Carlos IdISSC, Inst Invest, Madrid 28040, Spain
Varela, P:
Hosp Univ Cabuenes, Gijon 33203, Spain
de Francisco, R:
Hosp Univ Cent Asturias, Inst Invest Biosanitaria Principado Asturias ISPA, Oviedo 33011, Spain
Monfort, D:
Consorci Sanitari Terrassa, Terrassa 08227, Spain
Arriero, GM:
Complejo Hosp Univ Ferrol, Ferrol 15405, Spain
Hernandez-Camba, A:
Hosp Univ Nuestra Senora de Candelaria, Santa Cruz De Tenerife 38010, Spain
Alonso, FJG:
Hosp Univ Rio Hortega, Valladolid 47012, Spain
Van Domselaar, M:
Hosp Univ Torrejon, Torrejon De Ardoz 28850, Spain
Pajares-Villarroya, R:
Hosp Univ Infanta Sofia, San Sebastian Los Reyes 28702, Spain
Nunez, A:
Hosp Clin Univ Salamanca, Salamanca 37007, Spain
Moranta, FR:
Hosp Univ Bellvitge, Lhospitalet De Llobregat 08907, Spain
Marin-Jimenez, I:
Hosp Univ Gregorio Maranon, Madrid 28009, Spain
Alonso, VR:
Hosp Univ Vall dHebron, Barcelona 08035, Spain
Rodriguez, MDM:
Hosp Univ Virgen de las Nieves, Granada 18014, Spain
Camo-Monterde, P:
Hosp Univ San Jorge, Huesca 22004, Spain
Tercero, IG:
Hosp Gen Univ Santa Lucia, Cartagena 30202, Spain
Navarro-Llavat, M:
Hosp St Joan Despi Moises Broggi, St Joan Despi 08970, Spain
Garcia, LA:
Hosp Univ Burgos, Burgos 09006, Spain
Cruz, DH:
Hosp Gen Univ Ciudad Real, Ciudad Real 13005, Spain
Kloss, S:
Janssen, EMEA, B-2340 Beerse, Belgium
Passey, A:
Janssen, EMEA, B-2340 Beerse, Belgium
Novella, C:
Janssen Med Dept, Paseo Doce Estrellas 5-7, Madrid 28042, Spain
Vispo, E:
Janssen Med Dept, Paseo Doce Estrellas 5-7, Madrid 28042, Spain
Barreiro-de Acosta, M:
Complejo Hosp Univ Santiago, Santiago De Compostela 15706, Spain
Gisbert, JP:
Univ Autonoma Madrid, Hosp Univ La Princesa, Inst Invest Sanitaria Princesa IIS IP, Madrid 28006, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Madrid 28029, Spain
Green Published, gold, All Open Access, Gold, Green
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