Carlos Taxonera1,2, Manuel Barreiro-de Acosta3, Marta Calvo4, Cristina Saro5, Guillermo Bastida6, María D Martín-Arranz7, Javier P Gisbert8,9, Valle García-Sánchez10, Ignacio Marín-Jiménez11, Fernando Bermejo12, María Chaparro13,14, Ángel Ponferrada15, María P Martínez-Montiel16, Ramón Pajares17, Celia de Gracia18, David Olivares19,20, Cristina Alba21,22, Juan L Mendoza23,24, Ignacio Fernández-Blanco25. 1. Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain. carlos.taxonera@salud.madrid.org. 2. Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. carlos.taxonera@salud.madrid.org. 3. Department of Gastroenterology, Hospital Clínico de Santiago, Santiago de Compostela, Spain. manubarreiro@hotmail.com. 4. Department of Gastroenterology, Hospital Puerta de Hierro, Madrid, Spain. calvo.marta@gmail.com. 5. Department of Gastroenterology, Hospital de Cabueñes, Gijón, Spain. csarog@telefonica.net. 6. Department of Gastroenterology, Hospital La Fe, Valencia, Spain. guille.bastida@gmail.com. 7. Department of Gastroenterology, Hospital La Paz, Madrid, Spain. mmartinarranz@salud.madrid.org. 8. Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain. javier.p.gisbert@gmail.com. 9. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. javier.p.gisbert@gmail.com. 10. Department of Gastroenterology, Hospital Reina Sofía and IMIBIC, Universidad de Córdoba, Córdoba, Spain. vallegarciasanchez@gmail.com. 11. Department of Gastroenterology, Hospital Gregorio Marañón, Madrid, Spain. drnachomarin@hotmail.com. 12. Department of Gastroenterology, Hospital de Fuenlabrada, Madrid, Spain. fbermejo.hflr@salud.madrid.org. 13. Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain. mariachs2005@gmail.com. 14. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. mariachs2005@gmail.com. 15. Department of Gastroenterology, Hospital Infanta Leonor, Madrid, Spain. angelponmedicina@yahoo.es. 16. Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain. pilarmarmon123@telefonica.net. 17. Department of Gastroenterology, Hospital Infanta Sofía, Madrid, Spain. rpajaresvi@gmail.com. 18. Department of Gastroenterology, Hospital Gregorio Marañón, Madrid, Spain. celiadgf@hotmail.com. 19. Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain. david.olivares@salud.madrid.org. 20. Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. david.olivares@salud.madrid.org. 21. Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain. cristina.alba@telefonica.net. 22. Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. cristina.alba@telefonica.net. 23. Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain. juanluis.mendoza@salud.madrid.org. 24. Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. juanluis.mendoza@salud.madrid.org. 25. Inflammatory Bowel Disease Unit, Hospital Universitario Moncloa, Madrid, Spain. fernandezblanco@telefonica.net.
Abstract
BACKGROUND: The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated. AIMS: To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC. METHODS: This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis. RESULTS: Seventy-nine patients were included. Fifty-four patients (68.4%) achieved short-term clinical response and 41 patients (51.9%) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8%) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.12-0.49; p < 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4%) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95% CI 0.03-0.69; p < 0.007). CONCLUSIONS: In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70% of patients. In the long term, 58% of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86% reduction in the relative risk of colectomy.
BACKGROUND: The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated. AIMS: To assess the short- and long-term outcomes of infliximab dose escalation in a cohort of patients with UC. METHODS: This was a multicenter, retrospective, cohort study. All consecutive UC patients who had lost response to infliximab maintenance infusions and who underwent infliximab dose escalation were included. Post-escalation short-term clinical response and remission were evaluated. In the long term, the cumulative probabilities of infliximab failure-free survival and colectomy-free survival were calculated. Predictors of short-term response and event-free survival were estimated using logistic regression analysis and Cox proportional hazard regression analysis. RESULTS: Seventy-nine patients were included. Fifty-four patients (68.4%) achieved short-term clinical response and 41 patients (51.9%) entered in clinical remission. After a median follow-up of 15 months [interquartile range (IQR) 8-26], 33 patients (41.8%) had infliximab failure. Patients with short-term response had a significantly lower adjusted rate of infliximab failure [hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.12-0.49; p < 0.001]. During a median follow-up of 24 months (IQR 13-34), 9 patients (11.4%) needed colectomy. Short-term response was identified as a predictor of colectomy avoidance (HR 0.14; 95% CI 0.03-0.69; p < 0.007). CONCLUSIONS: In UC patients who lost response to infliximab during maintenance, infliximab dose escalation enabled recovery of short-term response in nearly 70% of patients. In the long term, 58% of patients maintained sustained clinical benefit, and 9 of 10 avoided colectomy. Short-term response was associated with an 86% reduction in the relative risk of colectomy.
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