title: Prevention of Antidrug Antibody Formation to Infliximab in Crohn's Patients With Prior Failure of Thiopurines.
abstract: Combination thiopurine-infliximab (IFX) therapy is associated with reduced generation of antidrug antibodies (ADA) compared with IFX monotherapy. Whether past clinical response to thiopurine therapy bears an effect on ADA prevention is unknown.
  
  
  
  This was a retrospective observational multicenter study of patients with Crohn's disease (CD) treated by IFX and thiopurines who had serial ADA measurements. Therapy was classified into past thiopurine response or its lack of, de novo combination, or IFX monotherapy. The primary endpoint was risk of ADA appearance.
  
  
  
  Out of 494 patients with serial ADA measurements 207 eligible patients were included in the final analysis. The 1-year cumulative risk of ADA development was similar in past thiopurine responders (19.3%) compared with past thiopurine failures (16.1%) (log rank P = .54). ADA was found in 46.6% of the monotherapy group and was significantly different compared with past thiopurine responders (P = .007) and past thiopurine failures (P = .007). The adjusted hazards for ADA development were significantly lower in past responders and past failures compared with the monotherapy group (hazard ratio, 0.47 [95% CI, 0.22-1.00] and 0.32 [95% CI, 0.11-0.93], respectively).
  
  
  
  Thiopurines-IFX cotherapy in patients with Crohn's disease is associated with reduced ADA formation compared with IFX monotherapy. This is probably regardless of initial thiopurine therapeutic effect.
authors.affiliation: Department of Internal Medicine H, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel. Electronic address: haggaiby@gmail.com.
authors.forename: Haggai
authors.initials: H
authors.lastname: Bar-Yoseph
authors.affiliation: Department of Gastroenterology, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Matti
authors.initials: M
authors.lastname: Waterman
authors.affiliation: Department of Epidemiology, Rambam Health Care Campus and School of Public Health, University of Haifa, Haifa, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Almog
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Billiet
authors.affiliation: Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Gastroenterology, Chaim Sheba Medical Center, Ramat-gan and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Ungar
authors.affiliation: IBD Center, Department of Gastroenterology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Henit
authors.initials: H
authors.lastname: Yanai
authors.affiliation: IBD Center, Department of Gastroenterology, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Dotan
authors.affiliation: Department of Gastroenterology, Chaim Sheba Medical Center, Ramat-gan and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
authors.affiliation: Department of Gastroenterology, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Chowers
mesh_terms: D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D003424:Crohn Disease / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000276:immunology*; D000069285:Infliximab / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; C488629:azathiopurine; D000069285:Infliximab; D015122:Mercaptopurine
keywords: Antidrug Antibodies; Crohn's Disease; Infliximab; Thiopurines