title: Adalimumab Maintenance Treatment in Ulcerative Colitis: Outcomes by Prior Anti-TNF Use and Efficacy of Dose Escalation.
abstract: The impact of prior anti-TNF use on "real-life" outcomes of adalimumab therapy in ulcerative colitis (UC) is not well known.
  
  
  
  To compare the influence of prior anti-TNF use on the outcomes of adalimumab maintenance treatment in UC patients. We also assessed the effectiveness of adalimumab dose escalation.
  
  
  
  This retrospective multicenter cohort study included consecutive UC who advanced to an adalimumab maintenance regimen. Patients in whom adalimumab was discontinued prior to week eight of treatment were excluded. The co-primary efficacy endpoints were the cumulative probabilities of adalimumab failure-free survival and colectomy-free survival. We also assessed the need for and the effectiveness of adalimumab dose escalation.
  
  
  
  Of 184 UC on maintenance treatment with adalimumab, 116 (63%) had previous anti-TNF use. After a median follow-up of 23 months (interquartile range 13-49), 112 patients (60%) maintained corticosteroid-free clinical response. Sixty-nine patients (37%) had adalimumab failure, and 22 (12%) needed colectomy. Anti-TNF-naïve patients had significantly lower adjusted rates of adalimumab failure (hazard ratio [HR] 0.65; p < 0.001), adalimumab dose escalation (HR 0.35; p = 0.002), and need for colectomy (HR 0.26; p < 0.004). Seventy-six patients (41%) needed dose escalation after secondary loss of response, and 47% of these regained response after escalation. Short-term response after escalation was identified as a significant predictor of colectomy avoidance (HR 0.53; p = 0.007).
  
  
  
  In this "real-life" cohort of UC patients on maintenance treatment with adalimumab, anti-TNF-naïve patients had significantly better long-term outcomes. Adalimumab dose escalation enabled recovery of response in nearly half of patients.
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 Sanitaria San Carlos (IdISSC), Madrid, Spain. carlos.taxonera@salud.madrid.org.
authors.forename: Carlos
authors.identifier: 0000-0001-9166-7350
authors.initials: C
authors.lastname: Taxonera
authors.affiliation: Hospital Reina Sofia, Córdoba, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Iglesias
authors.affiliation: Hospital Virgen Blanca, León, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Muñoz
authors.affiliation: Hospital Puerta de Hierro, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Calvo
authors.affiliation: Hospital Clínico, Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Barreiro-de Acosta
authors.affiliation: Hospital Josep Trueta, Girona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Busquets
authors.affiliation: Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Calvet
authors.affiliation: Hospital Clínico, Salamanca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rodríguez
authors.affiliation: Hospital Infanta Sofia, Madrid, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Pajares
authors.affiliation: Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain.|Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.affiliation: Hospital Universitario Fundación Alcorcón, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: López-Serrano
authors.affiliation: Hospital Universitario Fundación Alcorcón, Madrid, Spain.
authors.forename: José Luís
authors.initials: JL
authors.lastname: Pérez-Calle
authors.affiliation: Hospital Infanta Leonor, Madrid, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Ponferrada
authors.affiliation: Hospital de Cabueñes, Gijón, Spain.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: De la Coba
authors.affiliation: Hospital de Fuenlabrada, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bermejo
authors.affiliation: Corporació Sanitària Universitària Parc Taulí, Sabadell, Spain.|Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Chaparro
authors.affiliation: Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, 28040, Madrid, Spain.|Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
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.|Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alba
authors.affiliation: Hospital Moncloa, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Fernández-Blanco
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003082:Colectomy / Q000706:statistics & numerical data; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D057915:Drug Substitution; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab
keywords: Adalimumab; Colectomy; Dose escalation; Infliximab; Secondary loss of response; Ulcerative colitis