title: The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab.
abstract: OBJECTIVE
  To characterise the temporal evolution of antibodies to infliximab (ATI).
  
  
  METHODS
  Prospective observational study of infliximab-treated patients with inflammatory bowel disease between 2009 and 2012.
  
  
  METHODS
  Trough levels of infliximab and ATI were measured before each infusion by anti-λ ELISA. Patients were monitored for disease activity by clinical activity indexes and for dose-intensification or infliximab cessation. The occurrence of transient ATI disappearing spontaneously without intervention was recorded separately.
  
  
  RESULTS
  125 patients were included (98 Crohn's disease, 27 ulcerative colitis, median follow-up 11.5±22 months) and 1119 sera were analysed for infliximab and ATI levels. Kaplan-Meier analysis showed that 42% of patients remained ATI-free by 4 years of treatment. Most (90%) of the patients who developed ATI did so within the first 12 months of therapy, whereas transient ATI were detected throughout the duration of infliximab therapy (p<0.001). ATI incidence was similar between patients who received infliximab previously (episodic/interrupted therapy patients, n=14) and scheduled-therapy patients (n=111). In the scheduled group, combination immunomodulator+infliximab resulted in longer ATI-free survival compared with monotherapy (p=0.003, logrank test). Survival free of clinical loss of response was enjoyed by 51% of patients, and serial measurements showed that ATI development often preceded the onset of clinical flare.
  
  
  CONCLUSIONS
  When followed prospectively, most patients who develop ATI do so within the first 12 months of therapy. This incidence is reduced by concomitant immunomodulator even in scheduled-therapy patients. In contrast, transient ATI, which are of little clinical significance, can appear haphazardly at any time during treatment. The onset of clinical loss of response may lag behind the appearance of anti-infliximab antibodies.
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer & Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel.
authors.forename: Bella
authors.initials: B
authors.lastname: Ungar
authors.affiliation: Department of Gastroenterology, Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Chowers
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer & Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Yavzori
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer & Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Picard
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer & Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Fudim
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer & Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel.
authors.forename: Ofir
authors.initials: O
authors.lastname: Har-Noy
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer & Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Kopylov
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer & Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel.
authors.forename: Rami
authors.initials: R
authors.lastname: Eliakim
authors.affiliation: Department of Gastroenterology, Sheba Medical Center Tel Hashomer & Sackler School of Medicine, Tel-Aviv University, Ramat Gan, Israel.
authors.forename: Shomron
authors.initials: S
authors.lastname: Ben-Horin
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D000906:Antibodies / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology* / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology; D004351:Drug Resistance / Q000276:immunology*; D005260:Female; D006801:Humans; D000069285:Infliximab; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000069285:Infliximab
keywords: Ibd Clinical; Immunology; Infliximab