title: Adalimumab vs Azathioprine in the Prevention of Postoperative Crohn's Disease Recurrence. A GETECCU Randomised Trial.
abstract: OBJECTIVE
  Postoperative recurrence of Crohn's disease [POR-CD] is almost certain if no prophylaxis is administered. Evidence for optimal treatment is lacking. Our aim was to compare the efficacy of adalimumab [ADA] and azathioprine [AZA] in this setting.
  
  
  METHODS
  We performed a phase 3, 52-week, multicentre, randomised, superiority study [APPRECIA], in which patients with ileocolonic resection were randomised either to ADA 160-80-40 mg subcutaneously [SC] or AZA 2.5 mg/kg/day, both associated with metronidazole. The primary endpoint was endoscopic recurrence at 1 year [Rutgeerts i2b, i3, i4], as evaluated by a blinded central reader.
  
  
  RESULTS
  We recruited 91 patients [median age 35.0 years, disease duration 6.0 years, 23.8% smokers, 7.1% previous resections]. The study drugs were administered to 84 patients. Treatment was discontinued owing to adverse events in 11 patients [13.1%]. Discontinuation was significantly less frequent in the ADA [4.4%] than in the AZA group [23.2%] (dif.: 18.6% [95% CI 4.1-33.2], p = 0.011). According to the intention-to-treat analysis, therapy failed in 23/39 patients in the AZA group [59%] and 19/45 patients in the ADA group [42.2%] [p = 0.12]. In the per-protocol analysis [61 patients with centrally evaluable images], recurrence was recorded in 8/24 [33.3%] patients in the AZA and 11/37 [29.7%] in the ADA group [p = 0.76]. No statistically significant differences between the groups were found for recurrence in magnetic resonance images, biological markers of activity, surgical procedures, or hospital admissions.
  
  
  CONCLUSIONS
  ADA has not demonstrated a better efficacy than AZA [both associated with metronidazole] for prophylaxis of POR-CD in an unselected population, although tolerance to ADA is significantly better. ClinicalTrials.gov NCT01564823.
authors.affiliation: Gastroenterology-Hepatology Unit, Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Sanromán
authors.affiliation: Gastroenterology-Hepatology Unit, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Vera-Mendoza
authors.affiliation: Gastroenterology-Hepatology Unit, Hospital Germans Trias i Pujol, Badalona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Eugeni
authors.initials: E
authors.lastname: Domènech
authors.affiliation: Digestive Diseases Unit, Hospital Clínico San Carlos, Instituto Investigación Sanitaria San Carlos [IdISSC], Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Taxonera
authors.affiliation: General Surgery Unit, Hospital Universitario Puerto Real, Puerto Real, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Vega Ruiz
authors.affiliation: Digestive Diseases Unit, Hospital Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón [IiSGM], Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Marín-Jiménez
authors.affiliation: Gastroenterology-Hepatology Unit, Hospital Universitari de Bellvitge-IDIBELL, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Guardiola
authors.affiliation: Digestive Diseases Unit, Hospital Universitario Virgen de Macarena, Sevilla, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Castro
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.|Gastroenterology-Hepatology Unit, Hospital Universitari Mutua Terrassa, Terrassa, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Esteve
authors.affiliation: Digestive Diseases Unit, Hospital Reina Sofía, Córdoba, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Iglesias
authors.affiliation: Gastroenterology-Hepatology Unit, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ceballos
authors.affiliation: Digestive Diseases Unit, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez-Montiel
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.|Digestive Diseases Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria La Princesa [IIS-IP], Madrid, Spain.
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.affiliation: Digestive Diseases Unit, Hospital Clínic de Valencia, University of Valencia, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Mínguez
authors.affiliation: Digestive Diseases Unit, Hospital Arquitecto Marcide, Ferrol, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Echarri
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.|Digestive Diseases Unit, Corporació Sanitària Parc Taulí, Sabadell, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Calvet
authors.affiliation: Digestive Diseases Unit, Hospital Universitario Río Hortega, Valladolid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Barrio
authors.affiliation: Digestive Diseases Unit, Hospital de Manises, Valencia, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Hinojosa
authors.affiliation: Digestive Diseases Unit, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Martín-Arranz
authors.affiliation: Gastroenterology-Hepatology Unit, Hospital Del Mar, Barcelona, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Márquez-Mosquera
authors.affiliation: Digestive Diseases Unit, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bermejo
authors.affiliation: Radiology Unit, Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rimola
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.|Digestive Diseases Unit, Hospital Universitario y Politécnico de La Fe, Valencia, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Pons
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Instituto de Salud Carlos III, Madrid, Spain.|Digestive Diseases Unit, Hospital Universitario y Politécnico de La Fe, Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Nos
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D003424:Crohn Disease / Q000517:prevention & control* / Q000601:surgery; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011182:Postoperative Care / Q000379:methods; D055502:Secondary Prevention / Q000379:methods
chemical_list: D007166:Immunosuppressive Agents; D000068879:Adalimumab; D001379:Azathioprine
keywords: Crohn’s disease; adalimumab; azathioprine