title: Undetectable anti-TNF drug levels in patients with long-term remission predict successful drug withdrawal.
abstract: BACKGROUND
  Low drug levels are associated with emerging loss of response to anti-TNF. However, this may not be the case in patients with long-term remission.
  
  
  OBJECTIVE
  To investigate the outcome of anti-TNF discontinuation in patients with long-term remission and incidental undetectable drug levels.
  
  
  METHODS
  A retrospective cohort study examining the duration of relapse-free survival in IBD patients in remission who discontinued infliximab or adalimumab having undetectable drug levels.
  
  
  RESULTS
  Forty eight patients who discontinued anti-TNF while in remission and had available drug levels were identified in two centres in France and Israel (infliximab-treated 35, adalimumab-13, Crohn's disease 30, ulcerative colitis 18, mean treatment duration of 22.7 ± 12.4 months). Endoscopy/MRE before stopping showed absence of active inflammation in 40/42 (95%) of evaluated patients, while inflammatory biomarkers (CRP and/or Calprotectin) were completely normal in only 31/48 (65%) of patients. During 12 months median follow-up, relapse occurred in 16/20 (80%) of patients who stopped anti-TNF while having measurable drug levels compared with 9/28 (32%) of patients who had undetectable drug levels (OR: 8.4, 95% CI: 2.2-32, P = 0.002). Relapse-free survival after anti-TNF cessation was significantly longer in patients with absent drug compared to those with detectable drug (P < 0.001, log rank test). On multivariate analysis, a patient's decision to stop therapy was weakly associated and abnormal inflammatory biomarkers and detectable drug levels were both strongly and independently associated with a higher risk of relapse after drug discontinuation.
  
  
  CONCLUSIONS
  Incidental finding of undetectable anti-TNF drug levels in patients with stable long-term deep remission may identify a subset of patients whose clinical remission is no longer dependent on anti-TNF treatment.
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel.|Sackler School of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Ben-Horin
authors.affiliation: Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Haifa, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Chowers
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Ungar
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel.|Sackler School of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.
authors.forename: U
authors.initials: U
authors.lastname: Kopylov
authors.affiliation: Sackler School of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.|Institute of Clinical Pharmacology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Loebstein
authors.affiliation: Sackler School of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.|Edmond & Lily Safra Children's Hospital, Tel Hashomer, Israel.
authors.forename: B
authors.initials: B
authors.lastname: Weiss
authors.affiliation: Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel.|Sackler School of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Eliakim
authors.affiliation: Department of Gastro-Enterology, INSERM CIC 1408, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Del Tedesco
authors.affiliation: Department of Immunology, INSERM CIC 1408, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Paul
authors.affiliation: Department of Gastro-Enterology, INSERM CIC 1408, Paris, France.
authors.forename: X
authors.initials: X
authors.lastname: Roblin
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D005602:France; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D000069285:Infliximab / Q000627:therapeutic use; D007557:Israel; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab