title: Infliximab Dose Escalation as an Effective Strategy for Managing Secondary Loss of Response in Ulcerative Colitis.
abstract: BACKGROUND
  The outcomes of infliximab dose escalation in ulcerative colitis (UC) have not been well evaluated.
  
  
  OBJECTIVE
  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.
authors.affiliation: 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.|Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. carlos.taxonera@salud.madrid.org.
authors.forename: Carlos
authors.initials: C
authors.lastname: Taxonera
authors.affiliation: Department of Gastroenterology, Hospital Clínico de Santiago, Santiago de Compostela, Spain. manubarreiro@hotmail.com.
authors.forename: Manuel
authors.initials: M
authors.lastname: Barreiro-de Acosta
authors.affiliation: Department of Gastroenterology, Hospital Puerta de Hierro, Madrid, Spain. calvo.marta@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Calvo
authors.affiliation: Department of Gastroenterology, Hospital de Cabueñes, Gijón, Spain. csarog@telefonica.net.
authors.forename: Cristina
authors.initials: C
authors.lastname: Saro
authors.affiliation: Department of Gastroenterology, Hospital La Fe, Valencia, Spain. guille.bastida@gmail.com.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Bastida
authors.affiliation: Department of Gastroenterology, Hospital La Paz, Madrid, Spain. mmartinarranz@salud.madrid.org.
authors.forename: María D
authors.initials: MD
authors.lastname: Martín-Arranz
authors.affiliation: Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain. javier.p.gisbert@gmail.com.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. javier.p.gisbert@gmail.com.
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.affiliation: Department of Gastroenterology, Hospital Reina Sofía and IMIBIC, Universidad de Córdoba, Córdoba, Spain. vallegarciasanchez@gmail.com.
authors.forename: Valle
authors.initials: V
authors.lastname: García-Sánchez
authors.affiliation: Department of Gastroenterology, Hospital Gregorio Marañón, Madrid, Spain. drnachomarin@hotmail.com.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Marín-Jiménez
authors.affiliation: Department of Gastroenterology, Hospital de Fuenlabrada, Madrid, Spain. fbermejo.hflr@salud.madrid.org.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bermejo
authors.affiliation: Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain. mariachs2005@gmail.com.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. mariachs2005@gmail.com.
authors.forename: María
authors.initials: M
authors.lastname: Chaparro
authors.affiliation: Department of Gastroenterology, Hospital Infanta Leonor, Madrid, Spain. angelponmedicina@yahoo.es.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Ponferrada
authors.affiliation: Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain. pilarmarmon123@telefonica.net.
authors.forename: María P
authors.initials: MP
authors.lastname: Martínez-Montiel
authors.affiliation: Department of Gastroenterology, Hospital Infanta Sofía, Madrid, Spain. rpajaresvi@gmail.com.
authors.forename: Ramón
authors.initials: R
authors.lastname: Pajares
authors.affiliation: Department of Gastroenterology, Hospital Gregorio Marañón, Madrid, Spain. celiadgf@hotmail.com.
authors.forename: Celia
authors.initials: C
authors.lastname: de Gracia
authors.affiliation: 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.|Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. david.olivares@salud.madrid.org.
authors.forename: David
authors.initials: D
authors.lastname: Olivares
authors.affiliation: Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain. cristina.alba@telefonica.net.|Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. cristina.alba@telefonica.net.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alba
authors.affiliation: 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.|Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain. juanluis.mendoza@salud.madrid.org.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Mendoza
authors.affiliation: Inflammatory Bowel Disease Unit, Hospital Universitario Moncloa, Madrid, Spain. fernandezblanco@telefonica.net.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Fernández-Blanco
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003082:Colectomy / Q000706:statistics & numerical data; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D016001:Confidence Intervals; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005765:Gastrointestinal Agents; D000069285:Infliximab
keywords: Cohort study; Colectomy; Dose escalation; Dose optimization; Infliximab; Ulcerative colitis